Ann Hsing

All Publications

• Racial/ethnic- and county-specific prevalence of chronic hepatitis B and its burden in California Hepatology, Medicine and Policy Toy, M., Wei, B., Virdi, T. S., Le, A., Trinh, H., Li, J., Zhang, J., Hsing, A. W., So, S. K., Nguyen, M. H. 2018; 3 (6)

  View details for DOI 10.1186/s41124-018-0034-7

• Salmonella enterica serovar Typhi and gallbladder cancer: a case-control study and meta-analysis. Cancer medicine Koshiol, J., Wozniak, A., Cook, P., Adaniel, C., Acevedo, J., Azócar, L., Hsing, A. W., Roa, J. C., Pasetti, M. F., Miquel, J. F., Levine, M. M., Ferreccio, C. 2016

  Abstract

  In Chile, where gallbladder cancer (GBC) rates are high and typhoid fever was endemic until the 1990s, we evaluated the association between Salmonella enterica serovar Typhi (S. Typhi) antibodies and GBC. We tested 39 GBC cases, 40 gallstone controls, and 39 population-based controls for S. Typhi Vi antibodies and performed culture and quantitative polymerase chain reaction for the subset with bile, gallstone, tissue, and stool samples available. We calculated gender and education-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the association with GBC. We also conducted a meta-analysis of >1000 GBC cases by combining our results with previous studies. GBC cases were more likely to have high Vi antibody titer levels than combined controls (OR: 4.0, 95% CI: 0.9-18.3), although S. Typhi was not recovered from bile, gallstone, tissue, or stool samples. In our meta-analysis, the summary relative risk was 4.6 (95% CI: 3.1-6.8, Pheterogeneity =0.6) for anti-Vi and 5.0 (95% CI: 2.7-9.3, Pheterogeneity  = 0.2) for bile or stool culture. Our results are consistent with the meta-analysis. Despite differences in study methods (e.g., S. Typhi detection assay), most studies found a positive association between S. Typhi and GBC. However, the mechanism underlying this association requires further investigation.

  View details for DOI 10.1002/cam4.915

  View details for PubMedID 27726295

  View details for PubMedCentralID PMC5119987

• Reduction of chronic hepatitis B-related hepatocellular carcinoma with anti-viral therapy, including low risk patients. Alimentary pharmacology & therapeutics LIN, D., Yang, H., Nguyen, N., Hoang, J., Kim, Y., Vu, V., Le, A., Chaung, K., Nguyen, V., Trinh, H., Li, J., Zhang, J., Hsing, A., Chen, C., Nguyen, M. H. 2016; 44 (8): 846-855

  Abstract

  Anti-viral therapy in chronic hepatitis B (CHB) is associated with a reduced risk of hepatocellular carcinoma (HCC) primary described in patients with cirrhosis.To examine the effects of treatment on HCC incidence in CHB with and without cirrhosis, after adjustment for background risks.A total of 2255 CHB patients from a US cohort (973 received anti-viral therapy) and 3653 patients from the community-based Taiwanese REVEAL-HBV study, none of whom received treatment. We used Cox proportional hazard models to calculate the risk of developing HCC after adjustment with the previously validated REACH-B risk score.We found 273 incident cases of HCC. After adjustment, therapy lowered the risk of HCC development in the US treated cohort when compared to the US untreated cohort (HR 0.31; 95% CI: 0.15-0.66; P = 0.002). HCC risk reduction was also confirmed when compared to the REVEAL cohort (HR 0.22; 95% CI: 0.12-0.40; P < 0.001). Each REACH-B point was associated with a 53% increased risk of HCC (HR 1.53; 95% CI 1.46-1.59; P < 0.001). We found a significant statistical reduction in HCC incidence with therapy regardless of gender, age, cirrhosis status, HBeAg serology, alanine aminotransferase level, REACH-B score or treatment medication. Therapy was beneficial to those with mildly- to moderately elevated HBV DNA levels (>2000 IU/mL) and of even greater benefit to those with levels >200 000 IU/mL.After adjustment for background risk, anti-viral therapy was associated with a significant reduction in HCC incidence in both community and real-life clinical cohorts, including in those patients previously thought to be at low risk.

  View details for DOI 10.1111/apt.13774

  View details for PubMedID 27549411

• Lipopolysaccharide-pathway proteins are associated with gallbladder cancer among adults in Shanghai, China with mediation by systemic inflammation. Annals of epidemiology Van Dyke, A. L., Kemp, T. J., Corbel, A. F., Zhu, B., Gao, Y., Wang, B., Rashid, A., Shen, M., Hildesheim, A., Hsing, A. W., Pinto, L. A., Koshiol, J. 2016; 26 (10): 704-709

  Abstract

  We examined inflammation as a mediator of associations between bacterial infection markers and gallbladder cancer (GBC).Bacterial response proteins (lipopolysaccharide [LPS], soluble cluster of differentiation 14 [sCD14], and LPS-binding protein [LBP]) were measured in 40 GBC cases and 126 gallstone controls with data on 63 serum inflammation markers. The relationships of LPS, LBP, and sCD14 with GBC were examined by logistic regression, which also was used to evaluate whether these associations are influenced by systemic inflammation as measured by a combinatorial inflammation score.The third versus the first tertiles of sCD14 and of LBP were associated with an increased GBC risk (odds ratio [95% confidence interval]: 5.41 [2.00-16.75] for sCD14, and 6.49 [2.24-23.79] for LBP). sCD14 and LBP were strongly associated with inflammation score (above vs. below the median), which itself was associated with a more than 21-fold increased risk of GBC for the third versus first tertiles. Associations between GBC and sCD14 and LBP were markedly attenuated when the inflammation score was included in the model. While LPS was not associated with GBC or inflammation, only 35% of cases and 22% of controls had detectable levels.These findings suggest that these LPS-pathway proteins are associated with GBC via inflammation-related pathways.

  View details for DOI 10.1016/j.annepidem.2016.08.009

  View details for PubMedID 27793274

  View details for PubMedCentralID PMC5123694

• Association of androgen metabolism gene polymorphisms with prostate cancer risk and androgen concentrations: Results from the Prostate Cancer Prevention Trial CANCER Price, D. K., Chau, C. H., Till, C., Goodman, P. J., Leach, R. J., Johnson-Pais, T. L., Hsing, A. W., Hoque, A., Parnes, H. L., Schenk, J. M., Tangen, C. M., Thompson, I. M., Reichardt, J. K., Figg, W. D. 2016; 122 (15): 2332-2340

  Abstract

  Prostate cancer is highly influenced by androgens and genes. The authors investigated whether genetic polymorphisms along the androgen biosynthesis and metabolism pathways are associated with androgen concentrations or with the risk of prostate cancer or high-grade disease from finasteride treatment.A nested case-control study from the Prostate Cancer Prevention Trial using data from men who had biopsy-proven prostate cancer (cases) and a group of biopsy-negative, frequency-matched controls was conducted to investigate the association of 51 single nucleotide polymorphisms (SNPs) in 12 genes of the androgen pathway with overall (total), low-grade, and high-grade prostate cancer incidence and serum hormone concentrations.There were significant associations of genetic polymorphisms in steroid 5α-reductase 1 (SRD5A1) (reference SNPs: rs3736316, rs3822430, rs1560149, rs248797, and rs472402) and SRD5A2 (rs2300700) with the risk of high-grade prostate cancer in the placebo arm of the Prostate Cancer Prevention Trial; 2 SNPs were significantly associated with an increased risk (SRD5A1 rs472402 [odds ratio, 1.70; 95% confidence interval, 1.05-2.75; Ptrend = .03] and SRD5A2 rs2300700 [odds ratio, 1.94; 95% confidence interval, 1.19-3.18; Ptrend = .01]). Eleven SNPs in SRD5A1, SRD5A2, cytochrome P450 family 1, subfamily B, polypeptide 1 (CYP1B1), and CYP3A4 were associated with modifying the mean concentrations of serum androgen and sex hormone-binding globulin; and 2 SNPs (SRD5A1 rs824811 and CYP1B1 rs10012; Ptrend < .05) consistently and significantly altered all androgen concentrations. Several SNPs (SRD5A1 rs3822430, SRD5A2 rs2300700, CYP3A43 rs800672, and CYP19 rs700519; Ptrend < .05) were significantly associated with both circulating hormone levels and prostate cancer risk.Germline genetic variations of androgen-related pathway genes are associated with serum androgen concentrations and the risk of prostate cancer. Further studies to examine the functional consequence of novel causal variants are warranted. Cancer 2016;122:2332-2340. © 2016 American Cancer Society.

  View details for DOI 10.1002/cncr.30071

  View details for PubMedID 27164191

• Prostate Cancer Susceptibility in Men of African Ancestry at 8q24. Journal of the National Cancer Institute Han, Y., Rand, K. A., Hazelett, D. J., Ingles, S. A., Kittles, R. A., Strom, S. S., Rybicki, B. A., Nemesure, B., Isaacs, W. B., Stanford, J. L., Zheng, W., Schumacher, F. R., Berndt, S. I., Wang, Z., Xu, J., Rohland, N., Reich, D., Tandon, A., Pasaniuc, B., Allen, A., Quinque, D., Mallick, S., Notani, D., Rosenfeld, M. G., Jayani, R. S., Kolb, S., Gapstur, S. M., Stevens, V. L., Pettaway, C. A., Yeboah, E. D., Tettey, Y., Biritwum, R. B., Adjei, A. A., Tay, E., Truelove, A., Niwa, S., Chokkalingam, A. P., John, E. M., Murphy, A. B., Signorello, L. B., Carpten, J., Leske, M. C., Wu, S., Hennis, A. J., Neslund-Dudas, C., Hsing, A. W., Chu, L., Goodman, P. J., Klein, E. A., Zheng, S. L., Witte, J. S., Casey, G., Lubwama, A., Pooler, L. C., Sheng, X., Coetzee, G. A., Cook, M. B., Chanock, S. J., Stram, D. O., Watya, S., Blot, W. J., Conti, D. V., Henderson, B. E., Haiman, C. A. 2016; 108 (7)

  Abstract

  The 8q24 region harbors multiple risk variants for distinct cancers, including >8 for prostate cancer. In this study, we conducted fine mapping of the 8q24 risk region (127.8-128.8Mb) in search of novel associations with common and rare variation in 4853 prostate cancer case patients and 4678 control subjects of African ancestry. All statistical tests were two-sided. We identified three independent associations at P values of less than 5.00×10(-8), all of which were replicated in studies from Ghana and Uganda (combined sample = 5869 case patients, 5615 control subjects; rs114798100: risk allele frequency [RAF] = 0.04, per-allele odds ratio [OR] = 2.31, 95% confidence interval [CI] = 2.04 to 2.61, P = 2.38×10(-40); rs72725879: RAF = 0.33, OR = 1.37, 95% CI = 1.30 to 1.45, P = 3.04×10(-27); and rs111906932: RAF = 0.03, OR = 1.79, 95% CI = 1.53 to 2.08, P = 1.39×10(-13)). Risk variants rs114798100 and rs111906923 are only found in men of African ancestry, with rs111906923 representing a novel association signal. The three variants are located within or near a number of prostate cancer-associated long noncoding RNAs (lncRNAs), including PRNCR1, PCAT1, and PCAT2. These findings highlight ancestry-specific risk variation and implicate prostate-specific lncRNAs at the 8q24 prostate cancer susceptibility region.

  View details for DOI 10.1093/jnci/djv431

  View details for PubMedID 26823525

• Association of inflammatory and other immune markers with gallbladder cancer: Results from two independent case-control studies. Cytokine Koshiol, J., Castro, F., Kemp, T. J., Gao, Y., Roa, J. C., Wang, B., Nogueira, L., Araya, J. C., Shen, M., Rashid, A., Hsing, A. W., Hildesheim, A., Ferreccio, C., Pfeiffer, R. M., Pinto, L. A. 2016; 83: 217-225

  Abstract

  Most gallbladder cancer (GBC) cases arise in the context of gallstones, which cause inflammation, but few gallstone patients develop GBC. We explored inflammation/immune-related markers measured in bile and serum in GBC cases compared to gallstone patients to better understand how inflammatory patterns in these two conditions differ. We measured 65 immune-related markers in serum and bile from 41 GBC cases and 127 gallstone patients from Shanghai, China, and calculated age- and sex-adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for GBC versus gallstones. We then focused on the markers that were significantly elevated in bile and serum to replicate the findings in serum from 35 GBC cases and 31 gallstone controls from Chile. Comparing the highest versus lowest quantile, 15 markers (23%) were elevated in both serum and bile from GBC versus gallstone patients in the Shanghai study (p<0.05). The strongest OR was for CXCL8 (interleukin-8) in serum (96.8, 95% CI: 11.9-790.2). Of these 15 markers, 6 were also significantly elevated in serum from Chile (CCL20, C-reactive protein, CXCL8, CXCL10, resistin, serum amyloid A). Pooled ORs from Shanghai and Chile for these 6 markers ranged from 7.2 (95% CI: 2.8-18.4) for CXCL10 to 58.2 (95% CI: 12.4-273.0) for CXCL8. GBC is associated with inflammation above and beyond that generated by gallstones alone. This local inflammatory process is reflected systemically. Future longitudinal studies are needed to identify the key players in cancer development, which may guide translational efforts to identify individuals at high risk of developing GBC.

  View details for DOI 10.1016/j.cyto.2016.05.003

  View details for PubMedID 27173614

• Association of inflammatory and other immune markers with gallbladder cancer: Results from two independent case-control studies CYTOKINE Koshiol, J., Castro, F., Kemp, T. J., Gao, Y., Carlos Roa, J., Wang, B., Nogueira, L., Carlos Araya, J., Shen, M., Rashid, A., Hsing, A. W., Hildesheim, A., Ferreccio, C., Pfeiffer, R. M., Pinto, L. A. 2016; 83: 217-225

  View details for DOI 10.1016/j.cyto.2016.05.003

  View details for Web of Science ID 000377228300029

• Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation NATURE COMMUNICATIONS Gusev, A., Shi, H., Kichaev, G., Pomerantz, M., Li, F., Long, H. W., Ingles, S. A., Kittles, R. A., Strom, S. S., Rybicki, B. A., Nemesure, B., Isaacs, W. B., Zheng, W., Pettaway, C. A., Yeboah, E. D., Tettey, Y., Biritwum, R. B., Adjei, A. A., Tay, E., Truelove, A., Niwa, S., Chokkalingam, A. P., John, E. M., Murphy, A. B., Signorello, L. B., Carpten, J., Leske, M. C., Wu, S., Hennis, A. J., Neslund-Dudas, C., Hsing, A. W., Chu, L., Goodman, P. J., Klein, E. A., Witte, J. S., Casey, G., Kaggwa, S., Cook, M. B., Stram, D. O., Blot, W. J., Eeles, R. A., Easton, D., Kote-Jarai, Z., Al Olama, A. A., Benlloch, S., Muir, K., Giles, G. G., Southey, M. C., FitzGerald, L. M., Gronberg, H., Wiklund, F., Aly, M., Henderson, B. E., Schleutker, J., Wahlfors, T., Tammela, T. L., Nordestgaard, B. G., Key, T. J., Travis, R. C., Neal, D. E., Donovan, J. L., Hamdy, F. C., Pharoah, P., Pashayan, N., Khaw, K., Stanford, J. L., Thibodeau, S. N., McDonnell, S. K., Schaid, D. J., Maier, C., Vogel, W., Luedeke, M., Herkommer, K., Kibel, A. S., Cybulski, C., Wokolorczyk, D., Kluzniak, W., Cannon-Albright, L., Teerlink, C., Brenner, H., Dieffenbach, A. K., Arndt, V., Park, J. Y., Sellers, T. A., Lin, H., Slavov, C., Kaneva, R., Mitev, V., Batra, J., Spurdle, A., Clements, J. A., Teixeira, M. R., Pandha, H., Michael, A., Paulo, P., Maia, S., Kierzek, A., Conti, D. V., Albanes, D., Berg, C., Berndt, S. I., Campa, D., Crawford, E. D., Diver, W. R., Gapstur, S. M., Gaziano, J. M., Giovannucci, E., Hoover, R., Hunter, D. J., Johansson, M., Kraft, P., Le Marchand, L., Lindstrom, S., Navarro, C., Overvad, K., Riboli, E., Siddiq, A., Stevens, V. L., Trichopoulos, D., Vineis, P., Yeager, M., Trynka, G., Raychaudhuri, S., Schumacher, F. R., Price, A. L., Freedman, M. L., Haiman, C. A., Pasaniuc, B., Cook, M., Guy, M., Govindasami, K., Leongamornlert, D., Sawyer, E. J., Wilkinson, R., Saunders, E. J., Tymrakiewicz, M., Dadaev, T., Morgan, A., Fisher, C., Hazel, S., Livni, N., Lophatananon, A., Pedersen, J., Hopper, J. L., Adolfson, J., Stattin, P., Johansson, J., Cavalli-Bjoerkman, C., Karlsson, A., Broms, M., Auvinen, A., Kujala, P., Maeaettaenen, L., Murtola, T., Taari, K., Weischer, M., Nielsen, S. F., Klarskov, P., Roder, A., Iversen, P., Wallinder, H., Gustafsson, S., Cox, A., Brown, P., George, A., Marsden, G., Lane, A., Davis, M., Zheng, W., Signorello, L. B., Blot, W. J., Tillmans, L., Riska, S., Wang, L., Rinckleb, A., Lubiski, J., Stegmaier, C., Pow-Sang, J., Park, H., Radlein, S., Rincon, M., Haley, J., Zachariah, B., Kachakova, D., Popov, E., Mitkova, A., Vlahova, A., Dikov, T., Christova, S., Heathcote, P., Wood, G., Malone, G., Saunders, P., Eckert, A., Yeadon, T., Kerr, K., Collins, A., Turner, M., Srinivasan, S., Kedda, M., Alexander, K., Omara, T., Wu, H., Henrique, R., Pinto, P., Santos, J., Barros-Silva, J. 2016; 7

  Abstract

  Although genome-wide association studies have identified over 100 risk loci that explain ∼33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integrating functional annotation with genetic data to understand the genetic basis of PrCa.

  View details for DOI 10.1038/ncomms10979

  View details for PubMedID 27052111

• Serum androgens and prostate cancer risk: results from the placebo arm of the Prostate Cancer Prevention Trial CANCER CAUSES & CONTROL Schenk, J. M., Till, C., Hsing, A. W., Stanczyk, F. Z., Gong, Z., Neuhouser, M. L., Reichardt, J. K., Hoque, A. M., Figg, W. D., Goodman, P. J., Tangen, C. M., Thompson, I. M. 2016; 27 (2): 175-182

  Abstract

  Compelling and long-standing data suggest that androgens play an important role in the development of both normal prostate epithelium and prostate cancer. Although testosterone administration can induce prostate cancer (PCA) in laboratory animals, serum-based epidemiologic studies examining androgens in humans have not consistently supported a role for androgens in prostate carcinogenesis. We examined whether pre-diagnostic serum androgens were associated with PCA risk in the placebo arm of the Prostate Cancer Prevention Trial.In this nested case-control study, cases (n = 1,032) were primarily local-stage, biopsy-detected cancers, and controls (n = 1,025) were biopsy-confirmed to be PCA-free. Pre-diagnostic serum androgens (total testosterone, 3α-androstanediol glucuronide, free testosterone), estrogen-to-testosterone ratio, and sex hormone-binding globulin (SHBG) concentrations were measured in pooled (baseline and year 3) blood samples.We found no significant associations between serum androgens, estrogen-to-testosterone ratios, or SHBG and risk of total, low (Gleason <7) or high-grade (Gleason 7-10) PCA.Much remains to be learned about the role of androgens in prostate carcinogenesis. Further research is needed to evaluate the role of androgens, timing of exposure, genetic modulators of androgen metabolism, or environmental exposures that may affect androgen influence on prostate carcinogenesis.

  View details for DOI 10.1007/s10552-015-0695-0

  View details for PubMedID 26589415

• Korean National Health Insurance Database Reply JAMA INTERNAL MEDICINE Hsing, A., Ioannidis, J. P. 2016; 176 (1): 138-139

  View details for PubMedID 26747668

• Del1 Knockout Mice Developed More Severe Osteoarthritis Associated with Increased Susceptibility of Chondrocytes to Apoptosis. PloS one Wang, Z., Tran, M. C., Bhatia, N. J., Hsing, A. W., Chen, C., LaRussa, M. F., Fattakhov, E., Rashidi, V., Jang, K. Y., Choo, K. J., Nie, X., Mathy, J. A., Longaker, M. T., Dauskardt, R. H., Helms, J. A., Yang, G. P. 2016; 11 (8)

  Abstract

  We identified significant expression of the matricellular protein, DEL1, in hypertrophic and mature cartilage during development. We hypothesized that this tissue-specific expression indicated a biological role for DEL1 in cartilage biology.Del1 KO and WT mice had cartilage thickness evaluated by histomorphometry. Additional mice underwent medial meniscectomy to induce osteoarthritis, and were assayed at 1 week for apoptosis by TUNEL staining and at 8 weeks for histology and OA scoring. In vitro proliferation and apoptosis assays were performed on primary chondrocytes.Deletion of the Del1 gene led to decreased amounts of cartilage in the ears and knee joints in mice with otherwise normal skeletal morphology. Destabilization of the knee led to more severe OA compared to controls. In vitro, DEL1 blocked apoptosis in chondrocytes.Osteoarthritis is among the most prevalent diseases worldwide and increasing in incidence as our population ages. Initiation begins with an injury resulting in the release of inflammatory mediators. Excessive production of inflammatory mediators results in apoptosis of chondrocytes. Because of the limited ability of chondrocytes to regenerate, articular cartilage deteriorates leading to the clinical symptoms including severe pain and decreased mobility. No treatments effectively block the progression of OA. We propose that direct modulation of chondrocyte apoptosis is a key variable in the etiology of OA, and therapies aimed at preventing this important step represent a new class of regenerative medicine targets.

  View details for DOI 10.1371/journal.pone.0160684

  View details for PubMedID 27505251

• Sleep Duration and Cancer in the NIH-AARP Diet and Health Study Cohort. PloS one Gu, F., Xiao, Q., Chu, L. W., Yu, K., Matthews, C. E., Hsing, A. W., Caporaso, N. E. 2016; 11 (9)

  Abstract

  Very few studies have examined sleep duration in relation to cancer incidence with the exception of breast cancer.We assessed the associations between sleep duration and incidences of total and 18 site-specific cancers in the NIH-AARP Health and Diet Study cohort, with 173,327 men and 123,858 women aged 51-72 years at baseline. Self-reported sleep duration categories were assessed via questionnaire. We used multivariable Cox proportional hazards regression to estimate hazard ratios (HR) and 95% confidence intervals (CI), using 7-8 hours/night as the reference.We observed a significantly increased risk of stomach cancer among male short sleepers (multivariable HR5-6 vs. 7-8 hours = 1.29; 95%CI: 1.05, 1.59; Ptrend = 0.03). We also observed suggestive associations in either short or long sleepers, which did not reach overall significance (Ptrend >0.05), including increased risks in male short sleepers for cancers of head and neck (HR<5vs.7-8 hours = 1.39; 95%CI:1.00-1.95), bladder (HR5-6vs.7-8 hours = 1.10; 95%CI:1.00-1.20), thyroid (HR<5 vs. 7-8 hours = 2.30; 95%CI:1.06, 5.02), Non-Hodgkin Lymphoma (NHL) (HR5-6vs.7-8 hours = 1.17; 95%CI:1.02-1.33), and myeloma (HR<5vs.7-8 hours = 2.06; 95%CI:1.20-3.51). In women, the suggestive associations include a decreased total cancer risk (HR<5vs.7-8 hours = 0.9; 95%CI:0.83-0.99) and breast cancer risk (HR<5vs.7-8 hours = 0.84; 95%CI:0.71-0.98) among short sleepers. A decreased ovarian cancer risk (HR≥ 9 vs. 7-8 hours = 0.50; 95%CI:0.26-0.97) and an increased NHL risk (HR≥ 9 vs. 7-8 hours = 1.45; 95%CI:1.00-2.11) were observed among long sleepers.In an older population, we observed an increased stomach cancer risk in male short sleepers and suggestive associations with short or long sleep duration for many cancer risks in both genders.

  View details for DOI 10.1371/journal.pone.0161561

  View details for PubMedID 27611440

• Integration of multiethnic fine-mapping and genomic annotation to prioritize candidate functional SNPs at prostate cancer susceptibility regions. Human molecular genetics Han, Y., Hazelett, D. J., Wiklund, F., Schumacher, F. R., Stram, D. O., Berndt, S. I., Wang, Z., Rand, K. A., Hoover, R. N., Machiela, M. J., Yeager, M., Burdette, L., Chung, C. C., Hutchinson, A., Yu, K., Xu, J., Travis, R. C., Key, T. J., Siddiq, A., Canzian, F., Takahashi, A., Kubo, M., Stanford, J. L., Kolb, S., Gapstur, S. M., Diver, W. R., Stevens, V. L., Strom, S. S., Pettaway, C. A., Al Olama, A. A., Kote-Jarai, Z., Eeles, R. A., Yeboah, E. D., Tettey, Y., Biritwum, R. B., Adjei, A. A., Tay, E., Truelove, A., Niwa, S., Chokkalingam, A. P., Isaacs, W. B., Chen, C., Lindstrom, S., Le Marchand, L., Giovannucci, E. L., Pomerantz, M., Long, H., Li, F., Ma, J., Stampfer, M., John, E. M., Ingles, S. A., Kittles, R. A., Murphy, A. B., Blot, W. J., Signorello, L. B., Zheng, W., Albanes, D., Virtamo, J., Weinstein, S., Nemesure, B., Carpten, J., Leske, M. C., Wu, S., Hennis, A. J., Rybicki, B. A., Neslund-Dudas, C., Hsing, A. W., Chu, L., Goodman, P. J., Klein, E. A., Zheng, S. L., Witte, J. S., Casey, G., Riboli, E., Li, Q., Freedman, M. L., Hunter, D. J., Gronberg, H., Cook, M. B., Nakagawa, H., Kraft, P., Chanock, S. J., Easton, D. F., Henderson, B. E., Coetzee, G. A., Conti, D. V., Haiman, C. A. 2015; 24 (19): 5603-5618

  Abstract

  Interpretation of biological mechanisms underlying genetic risk associations for prostate cancer is complicated by the relatively large number of risk variants (n = 100) and the thousands of surrogate SNPs in linkage disequilibrium. Here, we combined three distinct approaches: multiethnic fine-mapping, putative functional annotation (based upon epigenetic data and genome-encoded features), and expression quantitative trait loci (eQTL) analyses, in an attempt to reduce this complexity. We examined 67 risk regions using genotyping and imputation-based fine-mapping in populations of European (cases/controls: 8600/6946), African (cases/controls: 5327/5136), Japanese (cases/controls: 2563/4391) and Latino (cases/controls: 1034/1046) ancestry. Markers at 55 regions passed a region-specific significance threshold (P-value cutoff range: 3.9 × 10(-4)-5.6 × 10(-3)) and in 30 regions we identified markers that were more significantly associated with risk than the previously reported variants in the multiethnic sample. Novel secondary signals (P < 5.0 × 10(-6)) were also detected in two regions (rs13062436/3q21 and rs17181170/3p12). Among 666 variants in the 55 regions with P-values within one order of magnitude of the most-associated marker, 193 variants (29%) in 48 regions overlapped with epigenetic or other putative functional marks. In 11 of the 55 regions, cis-eQTLs were detected with nearby genes. For 12 of the 55 regions (22%), the most significant region-specific, prostate-cancer associated variant represented the strongest candidate functional variant based on our annotations; the number of regions increased to 20 (36%) and 27 (49%) when examining the 2 and 3 most significantly associated variants in each region, respectively. These results have prioritized subsets of candidate variants for downstream functional evaluation.

  View details for DOI 10.1093/hmg/ddv269

  View details for PubMedID 26162851

• Nationwide Population Science: Lessons From the Taiwan National Health Insurance Research Database. JAMA internal medicine Hsing, A. W., Ioannidis, J. P. 2015; 175 (9): 1527-1529

  View details for DOI 10.1001/jamainternmed.2015.3540

  View details for PubMedID 26192815

• Methodological Considerations in Estimation of Phenotype Heritability Using Genome-Wide SNP Data, Illustrated by an Analysis of the Heritability of Height in a Large Sample of African Ancestry Adults PLOS ONE Chen, F., He, J., Zhang, J., Chen, G. K., Thomas, V., Ambrosone, C. B., Bandera, E. V., Berndt, S. I., Bernstein, L., Blot, W. J., Cai, Q., Carpten, J., Casey, G., Chanock, S. J., Cheng, I., Chu, L., Deming, S. L., Driver, W. R., Goodman, P., Hayes, R. B., Hennis, A. J., Hsing, A. W., Hu, J. J., Ingles, S. A., John, E. M., Kittles, R. A., Kolb, S., Leske, M. C., Millikan, R. C., Monroe, K. R., Murphy, A., Nemesure, B., Neslund-Dudas, C., Nyante, S., Ostrander, E. A., Press, M. F., Rodriguez-Gil, J. L., Rybicki, B. A., Schumacher, F., Stanford, J. L., Signorello, L. B., Strom, S. S., Stevens, V., Van Den Berg, D., Wang, Z., Witte, J. S., Wu, S., Yamamura, Y., Zheng, W., Ziegler, R. G., Stram, A. H., Kolonel, L. N., Le Marchand, L., Henderson, B. E., Haiman, C. A., Stram, D. O. 2015; 10 (6)

  Abstract

  Height has an extremely polygenic pattern of inheritance. Genome-wide association studies (GWAS) have revealed hundreds of common variants that are associated with human height at genome-wide levels of significance. However, only a small fraction of phenotypic variation can be explained by the aggregate of these common variants. In a large study of African-American men and women (n = 14,419), we genotyped and analyzed 966,578 autosomal SNPs across the entire genome using a linear mixed model variance components approach implemented in the program GCTA (Yang et al Nat Genet 2010), and estimated an additive heritability of 44.7% (se: 3.7%) for this phenotype in a sample of evidently unrelated individuals. While this estimated value is similar to that given by Yang et al in their analyses, we remain concerned about two related issues: (1) whether in the complete absence of hidden relatedness, variance components methods have adequate power to estimate heritability when a very large number of SNPs are used in the analysis; and (2) whether estimation of heritability may be biased, in real studies, by low levels of residual hidden relatedness. We addressed the first question in a semi-analytic fashion by directly simulating the distribution of the score statistic for a test of zero heritability with and without low levels of relatedness. The second question was addressed by a very careful comparison of the behavior of estimated heritability for both observed (self-reported) height and simulated phenotypes compared to imputation R2 as a function of the number of SNPs used in the analysis. These simulations help to address the important question about whether today's GWAS SNPs will remain useful for imputing causal variants that are discovered using very large sample sizes in future studies of height, or whether the causal variants themselves will need to be genotyped de novo in order to build a prediction model that ultimately captures a large fraction of the variability of height, and by implication other complex phenotypes. Our overall conclusions are that when study sizes are quite large (5,000 or so) the additive heritability estimate for height is not apparently biased upwards using the linear mixed model; however there is evidence in our simulation that a very large number of causal variants (many thousands) each with very small effect on phenotypic variance will need to be discovered to fill the gap between the heritability explained by known versus unknown causal variants. We conclude that today's GWAS data will remain useful in the future for causal variant prediction, but that finding the causal variants that need to be predicted may be extremely laborious.

  View details for DOI 10.1371/journal.pone.0131106

  View details for Web of Science ID 000358151300033

  View details for PubMedCentralID PMC4488332

• Epidemiology of GIST in the Era of Histology Codes--Letter. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology Lin, A., Hsing, A. W., Ravdin, P. M. 2015; 24 (6): 998-?

  View details for DOI 10.1158/1055-9965.EPI-15-0001

  View details for PubMedID 26033756

• Preanalytical considerations in the design of clinical trials and epidemiological studies. Clinical chemistry Kellogg, M. D., Ellervik, C., Morrow, D., Hsing, A., Stein, E., Sethi, A. A. 2015; 61 (6): 797-803

  View details for DOI 10.1373/clinchem.2014.226118

  View details for PubMedID 25901083

• Menopausal hormone use and ovarian cancer risk: individual participant meta-analysis of 52 epidemiological studies LANCET Gapstur, S. M., Patel, A. V., Banks, E., Dal Maso, L., Talamini, R., Chetrit, A., Hirsh-Yechezkel, G., Lubin, F., Sadetzki, S., Beral, V., Bull, D., Cairns, B., Crossley, B., Gaitskell, K., Goodill, A., Green, J., Hermon, C., Key, T., Moser, K., Reeves, G., Sitas, F., Collins, R., Peto, R., Gonzalez, C. A., Lee, N., Marchbanks, P., Ory, H. W., Peterson, H. B., Wingo, P. A., Martin, N., SILPISORNKOSOL, S., Theetranont, C., BOOSIRI, B., CHUTIVONGSE, S., Jimakorn, P., Virutamasen, P., Wongsrichanalai, C., Goodman, M. T., Lidegaard, O., Kjaer, S. K., Morch, L. S., Kjaer, S. K., Tjonneland, A., Byers, T., Rohan, T., Mosgaard, B., Vessey, M., Yeates, D., Freudenheim, J. L., TITUS, L. J., Chang-Claude, J., Kaaks, R., Anderson, K. E., Lazovich, D., Robien, K., Hampton, J., Newcomb, P. A., Rossing, M. A., Thomas, D. B., Weiss, N. S., Lokkegaard, E., Riboli, E., Clavel-Chapelon, F., Cramer, D., Hankinson, S. E., Tamimi, R. M., Tworoger, S. S., Franceschi, S., La Vecchia, C., Negri, E., Adami, H. O., Magnusson, C., Riman, T., Weiderpass, E., Wolk, A., Schouten, L. J., van den Brandt, P. A., CHANTARAKUL, N., KOETSAWANG, S., RACHAWAT, D., Palli, D., Black, A., Brinton, L. A., Freedman, D. M., Hartge, P., Hsing, A. W., Jnr, J. V., Lissowska, J., HOOVER, R. N., Schairer, C., Babb, C., Urban, M., Graff-Iversen, S., Selmer, R., Bain, C. J., Green, A. C., Purdie, D. M., Siskind, V., Webb, P. M., Moysich, K., McCann, S. E., Hannaford, P., Kay, C., Binns, C. W., Lee, A. H., Zhang, M., Ness, R. B., Nasca, P., Coogan, P. F., Palmer, J. R., Rosenberg, L., Whittemore, A., Katsouyanni, K., Trichopoulou, A., Trichopoulos, D., Tzonou, A., DABANCENS, A., Martinez, L., Molina, R., SALAS, O., Lurie, G., Carney, M. E., Wilkens, L. R., Hartman, L., Manjer, J., Olsson, H., Kumle, M., Grisso, J. A., Morgan, M., Wheeler, J. E., Edwards, R. P., Kelley, J. L., Modugno, F., Onland-Moret, N. C., Peeters, P. H., Casagrande, J., Pike, M. C., Wu, A. H., Canfell, K., Miller, A. B., Gram, I. T., Lund, E., McGowan, L., Shu, X. O., Zheng, W., Farley, T. M., Holck, S., MEIRIK, O., Risch, H. A. 2015; 385 (9980): 1835-1842

  Abstract

  Half the epidemiological studies with information about menopausal hormone therapy and ovarian cancer risk remain unpublished, and some retrospective studies could have been biased by selective participation or recall. We aimed to assess with minimal bias the effects of hormone therapy on ovarian cancer risk.Individual participant datasets from 52 epidemiological studies were analysed centrally. The principal analyses involved the prospective studies (with last hormone therapy use extrapolated forwards for up to 4 years). Sensitivity analyses included the retrospective studies. Adjusted Poisson regressions yielded relative risks (RRs) versus never-use.During prospective follow-up, 12 110 postmenopausal women, 55% (6601) of whom had used hormone therapy, developed ovarian cancer. Among women last recorded as current users, risk was increased even with <5 years of use (RR 1·43, 95% CI 1·31-1·56; p<0·0001). Combining current-or-recent use (any duration, but stopped <5 years before diagnosis) resulted in an RR of 1·37 (95% CI 1·29-1·46; p<0·0001); this risk was similar in European and American prospective studies and for oestrogen-only and oestrogen-progestagen preparations, but differed across the four main tumour types (heterogeneity p<0·0001), being definitely increased only for the two most common types, serous (RR 1·53, 95% CI 1·40-1·66; p<0·0001) and endometrioid (1·42, 1·20-1·67; p<0·0001). Risk declined the longer ago use had ceased, although about 10 years after stopping long-duration hormone therapy use there was still an excess of serous or endometrioid tumours (RR 1·25, 95% CI 1·07-1·46, p=0·005).The increased risk may well be largely or wholly causal; if it is, women who use hormone therapy for 5 years from around age 50 years have about one extra ovarian cancer per 1000 users and, if its prognosis is typical, about one extra ovarian cancer death per 1700 users.Medical Research Council, Cancer Research UK.

  View details for DOI 10.1016/S0140-6736(14)61687-1

  View details for Web of Science ID 000354184500027

  View details for PubMedID 25684585

  View details for PubMedCentralID PMC4427760

• Finasteride Concentrations and Prostate Cancer Risk: Results from the Prostate Cancer Prevention Trial PLOS ONE Chau, C. H., Price, D. K., Till, C., Goodman, P. J., Chen, X., Leach, R. J., Johnson-Pais, T. L., Hsing, A. W., Hoque, A., Tangen, C. M., Chu, L., Parnes, H. L., Schenk, J. M., Reichardt, J. K., Thompson, I. M., Figg, W. D. 2015; 10 (5)

  Abstract

  In the Prostate Cancer Prevention Trial (PCPT), finasteride reduced the risk of prostate cancer by 25%, even though high-grade prostate cancer was more common in the finasteride group. However, it remains to be determined whether finasteride concentrations may affect prostate cancer risk. In this study, we examined the association between serum finasteride concentrations and the risk of prostate cancer in the treatment arm of the PCPT and determined factors involved in modifying drug concentrations.Data for this nested case-control study are from the PCPT. Cases were drawn from men with biopsy-proven prostate cancer and matched controls. Finasteride concentrations were measured using a liquid chromatography-mass spectrometry validated assay. The association of serum finasteride concentrations with prostate cancer risk was determined by logistic regression. We also examine whether polymorphisms in the enzyme target and metabolism genes of finasteride are related to drug concentrations using linear regression.Among men with detectable finasteride concentrations, there was no association between finasteride concentrations and prostate cancer risk, low-grade or high-grade, when finasteride concentration was analyzed as a continuous variable or categorized by cutoff points. Since there was no concentration-dependent effect on prostate cancer, any exposure to finasteride intake may reduce prostate cancer risk. Of the twenty-seven SNPs assessed in the enzyme target and metabolism pathway, five SNPs in two genes, CYP3A4 (rs2242480; rs4646437; rs4986910), and CYP3A5 (rs15524; rs776746) were significantly associated with modifying finasteride concentrations. These results suggest that finasteride exposure may reduce prostate cancer risk and finasteride concentrations are affected by genetic variations in genes responsible for altering its metabolism pathway.ClinicalTrials.gov NCT00288106.

  View details for DOI 10.1371/journal.pone.0126672

  View details for Web of Science ID 000356768100139

  View details for PubMedCentralID PMC4425512

• Application of multiplex arrays for cytokine and chemokine profiling of bile. Cytokine Kemp, T. J., Castro, F. A., Gao, Y., Hildesheim, A., Nogueira, L., Wang, B., Sun, L., Shelton, G., Pfeiffer, R. M., Hsing, A. W., Pinto, L. A., Koshiol, J. 2015; 73 (1): 84-90

  Abstract

  Gallbladder disease is highly related to inflammation, but the inflammatory processes are not well understood. Bile provides a direct substrate in assessing the local inflammatory response that develops in the gallbladder. To assess the reproducibility of measuring inflammatory markers in bile, we designed a methods study of 69 multiplexed immune-related markers measured in bile obtained from gallstone patients.To evaluate assay performance, a total of 18 bile samples were tested twice within the same plate for each analyte, and the 18 bile samples were tested on two different days for each analyte. We used the following performance parameters: detectability, coefficient of variation (CV), intraclass correlation coefficient (ICC), and percent agreement (concordance among replicate measures above and below detection limit). Furthermore, we examined the association of analyte levels with gallstone characteristics such as type, numbers, and size.All but 3 analytes (Stem Cell Factor, SCF; Thrombopoietin, TPO; sIL-1RI) were detectable in bile. 52 of 69 (75.4%) analytes had detectable levels for at least 50% of the subjects tested. The within-plate CVs were ⩽25% for 53 of 66 (80.3%) detectable analytes, and across-plate CVs were ⩽25% for 32 of 66 (48.5%) detectable analytes. Moreover, 64 of 66 (97.0%) analytes had ICC values of at least 0.8. Lastly, the percent agreement was high between replicates for all of the analytes (median; within plate, 97.2%; across plate, 97.2%). In exploratory analyses, we assessed analyte levels by gallstone characteristics and found that levels for several analytes decreased with increasing size of the largest gallstone per patient.Our data suggest that multiplex assays can be used to reliably measure cytokines and chemokines in bile. In addition, gallstone size was inversely related to the levels of select analytes, which may aid in identifying critical pathways and mechanisms associated with the pathogenesis of gallbladder diseases.

  View details for DOI 10.1016/j.cyto.2015.01.033

  View details for PubMedID 25743242

  View details for PubMedCentralID PMC4382212

• Application of multiplex arrays for cytokine and chemokine profiling of bile CYTOKINE Kemp, T. J., Castro, F. A., Gao, Y., Hildesheim, A., Nogueira, L., Wang, B., Sun, L., Shelton, G., Pfeiffer, R. M., Hsing, A. W., Pinto, L. A., Koshiol, J. 2015; 73 (1): 84-90

  Abstract

  Gallbladder disease is highly related to inflammation, but the inflammatory processes are not well understood. Bile provides a direct substrate in assessing the local inflammatory response that develops in the gallbladder. To assess the reproducibility of measuring inflammatory markers in bile, we designed a methods study of 69 multiplexed immune-related markers measured in bile obtained from gallstone patients.To evaluate assay performance, a total of 18 bile samples were tested twice within the same plate for each analyte, and the 18 bile samples were tested on two different days for each analyte. We used the following performance parameters: detectability, coefficient of variation (CV), intraclass correlation coefficient (ICC), and percent agreement (concordance among replicate measures above and below detection limit). Furthermore, we examined the association of analyte levels with gallstone characteristics such as type, numbers, and size.All but 3 analytes (Stem Cell Factor, SCF; Thrombopoietin, TPO; sIL-1RI) were detectable in bile. 52 of 69 (75.4%) analytes had detectable levels for at least 50% of the subjects tested. The within-plate CVs were ⩽25% for 53 of 66 (80.3%) detectable analytes, and across-plate CVs were ⩽25% for 32 of 66 (48.5%) detectable analytes. Moreover, 64 of 66 (97.0%) analytes had ICC values of at least 0.8. Lastly, the percent agreement was high between replicates for all of the analytes (median; within plate, 97.2%; across plate, 97.2%). In exploratory analyses, we assessed analyte levels by gallstone characteristics and found that levels for several analytes decreased with increasing size of the largest gallstone per patient.Our data suggest that multiplex assays can be used to reliably measure cytokines and chemokines in bile. In addition, gallstone size was inversely related to the levels of select analytes, which may aid in identifying critical pathways and mechanisms associated with the pathogenesis of gallbladder diseases.

  View details for DOI 10.1016/j.cyto.2015.01.033

  View details for Web of Science ID 000353078500013

  View details for PubMedCentralID PMC4382212

• Tobacco and alcohol in relation to male breast cancer: an analysis of the male breast cancer pooling project consortium. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology Cook, M. B., Guénel, P., Gapstur, S. M., van den Brandt, P. A., Michels, K. B., Casagrande, J. T., Cooke, R., Van Den Eeden, S. K., Ewertz, M., Falk, R. T., Gaudet, M. M., Gkiokas, G., Habel, L. A., Hsing, A. W., Johnson, K., Kolonel, L. N., La Vecchia, C., Lynge, E., Lubin, J. H., McCormack, V. A., Negri, E., Olsson, H., Parisi, D., Petridou, E. T., Riboli, E., Sesso, H. D., Swerdlow, A., Thomas, D. B., Willett, W. C., Brinton, L. A. 2015; 24 (3): 520-531

  Abstract

  The etiology of male breast cancer is poorly understood, partly due to its relative rarity. Although tobacco and alcohol exposures are known carcinogens, their association with male breast cancer risk remains ill-defined.The Male Breast Cancer Pooling Project consortium provided 2,378 cases and 51,959 controls for analysis from 10 case-control and 10 cohort studies. Individual participant data were harmonized and pooled. Unconditional logistic regression was used to estimate study design-specific (case-control/cohort) ORs and 95% confidence intervals (CI), which were then combined using fixed-effects meta-analysis.Cigarette smoking status, smoking pack-years, duration, intensity, and age at initiation were not associated with male breast cancer risk. Relations with cigar and pipe smoking, tobacco chewing, and snuff use were also null. Recent alcohol consumption and average grams of alcohol consumed per day were also not associated with risk; only one subanalysis of very high recent alcohol consumption (>60 g/day) was tentatively associated with male breast cancer (ORunexposed referent = 1.29; 95% CI, 0.97-1.71; OR>0-<7 g/day referent = 1.36; 95% CI, 1.04-1.77). Specific alcoholic beverage types were not associated with male breast cancer. Relations were not altered when stratified by age or body mass index.In this analysis of the Male Breast Cancer Pooling Project, we found little evidence that tobacco and alcohol exposures were associated with risk of male breast cancer.Tobacco and alcohol do not appear to be carcinogenic for male breast cancer. Future studies should aim to assess these exposures in relation to subtypes of male breast cancer.

  View details for DOI 10.1158/1055-9965.EPI-14-1009

  View details for PubMedID 25515550

• Effect of Finasteride on Serum Androstenedione and Risk of Prostate Cancer Within the Prostate Cancer Prevention Trial: Differential Effect on High- and Low-grade Disease UROLOGY Hoque, A., Yao, S., Till, C., Kristal, A. R., Goodman, P. J., Hsing, A. W., Tangen, C. M., Platz, E. A., Stanczyk, F. Z., Reichardt, J. K., VanBokhoven, A., Neuhouser, M. L., Santella, R. M., Figg, W. D., Price, D. K., Parnes, H. L., Lippman, S. M., Ambrosone, C. B., Thompson, I. M. 2015; 85 (3): 616-620

  Abstract

  To evaluate the effect of finasteride on serum androst-4-ene-3,17-dione (androstenedione) and its association with prostate cancer risk among subjects who participated in the Prostate Cancer Prevention Trial.We analyzed serum androstenedione levels in 317 prostate cancer cases and 353 controls, nested in the Prostate Cancer Prevention Trial, a randomized placebo-controlled trial that found finasteride decreased prostate cancer risk. Androstenedione is the second most important circulating androgen in men besides testosterone and also a substrate for 5α-reductase enzyme.We observed a 22% increase in androstenedione levels compared with the baseline values in subjects who were treated with finasteride for 3 years. This significant increase did not vary by case-control status. Adjusted odds ratio and 95% confidence interval for the third tertile of absolute change in androstenedione levels compared with the first tertile were 0.42 (95% confidence interval, 0.19-0.94) for low-grade (Gleason score <7) cases. Similar results were observed when analyzed using percent change. There were no significant associations between serum androstenedione levels and the risk of high-grade disease.The results of this nested case-control study confirm that finasteride blocks the conversion of testosterone to dihydrotestosterone (DHT) and of androstenedione to 5α-androstanedione-3,17-dione, which also leads to the reduction of DHT formation. This decrease in DHT may help reduce the risk of low-grade prostate cancer in men. Our data on a differential effect of androstenedione also suggest that some high-grade prostate cancers may not require androgen for progression.

  View details for DOI 10.1016/j.urology.2014.11.024

  View details for Web of Science ID 000351942400034

  View details for PubMedID 25733274

• Generalizability of established prostate cancer risk variants in men of African ancestry. International journal of cancer. Journal international du cancer Han, Y., Signorello, L. B., Strom, S. S., Kittles, R. A., Rybicki, B. A., Stanford, J. L., Goodman, P. J., Berndt, S. I., Carpten, J., Casey, G., Chu, L., Conti, D. V., Rand, K. A., Diver, W. R., Hennis, A. J., John, E. M., Kibel, A. S., Klein, E. A., Kolb, S., Le Marchand, L., Leske, M. C., Murphy, A. B., Neslund-Dudas, C., Park, J. Y., Pettaway, C., Rebbeck, T. R., Gapstur, S. M., Zheng, S. L., Wu, S., Witte, J. S., Xu, J., Isaacs, W., Ingles, S. A., Hsing, A., Easton, D. F., Eeles, R. A., Schumacher, F. R., Chanock, S., Nemesure, B., Blot, W. J., Stram, D. O., Henderson, B. E., Haiman, C. A. 2015; 136 (5): 1210-1217

  Abstract

  Genome-wide association studies have identified more than 80 risk variants for prostate cancer, mainly in European or Asian populations. The generalizability of these variants in other racial/ethnic populations needs to be understood before the loci can be used widely in risk modeling. In our study, we examined 82 previously reported risk variants in 4,853 prostate cancer cases and 4,678 controls of African ancestry. We performed association testing for each variant using logistic regression adjusted for age, study and global ancestry. Of the 82 known risk variants, 68 (83%) had effects that were directionally consistent in their association with prostate cancer risk and 30 (37%) were significantly associated with risk at p < 0.05, with the most statistically significant variants being rs116041037 (p = 3.7 × 10(-26) ) and rs6983561 (p = 1.1 × 10(-16) ) at 8q24, as well as rs7210100 (p = 5.4 × 10(-8) ) at 17q21. By exploring each locus in search of better markers, the number of variants that captured risk in men of African ancestry (p < 0.05) increased from 30 (37%) to 44 (54%). An aggregate score comprised of these 44 markers was strongly associated with prostate cancer risk [per-allele odds ratio (OR) = 1.12, p = 7.3 × 10(-98) ]. In summary, the consistent directions of effects for the vast majority of variants in men of African ancestry indicate common functional alleles that are shared across populations. Further exploration of these susceptibility loci is needed to identify the underlying biologically relevant variants to improve prostate cancer risk modeling in populations of African ancestry.

  View details for DOI 10.1002/ijc.29066

  View details for PubMedID 25044450

• Tobacco and Alcohol in Relation to Male Breast Cancer: An Analysis of the Male Breast Cancer Pooling Project Consortium CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Cook, M. B., Guenel, P., Gapstur, S. M., van den Brandt, P. A., Michels, K. B., Casagrande, J. T., Cooke, R., Van Den Eeden, S. K., Ewertz, M., Falk, R. T., Gaudet, M. M., Gkiokas, G., Habel, L. A., Hsing, A. W., Johnson, K., Kolonel, L. N., La Vecchia, C., Lynge, E., Lubin, J. H., McCormack, V. A., Negri, E., Olsson, H., Parisi, D., Petridou, E. T., Riboli, E., Sesso, H. D., Swerdlow, A., Thomas, D. B., Willett, W. C., Brinton, L. A. 2015; 24 (3): 520-531

  View details for DOI 10.1158/1055-9965.EPI-14-1009

  View details for Web of Science ID 000351953100007

• Generalizability of established prostate cancer risk variants in men of African ancestry INTERNATIONAL JOURNAL OF CANCER Han, Y., Signorello, L. B., Strom, S. S., Kittles, R. A., Rybicki, B. A., Stanford, J. L., Goodman, P. J., Berndt, S. I., Carpten, J., Casey, G., Chu, L., Conti, D. V., Rand, K. A., Diver, W. R., Hennis, A. J., John, E. M., Kibel, A. S., Klein, E. A., Kolb, S., Le Marchand, L., Leske, M. C., Murphy, A. B., Neslund-Dudas, C., Park, J. Y., Pettaway, C., Rebbeck, T. R., Gapstur, S. M., Zheng, S. L., Wu, S., Witte, J. S., Xu, J., Isaacs, W., Ingles, S. A., Hsing, A., Easton, D. F., Eeles, R. A., Schumacher, F. R., Chanock, S., Nemesure, B., Blot, W. J., Stram, D. O., Henderson, B. E., Haiman, C. A. 2015; 136 (5): 1210-1217

  Abstract

  Genome-wide association studies have identified more than 80 risk variants for prostate cancer, mainly in European or Asian populations. The generalizability of these variants in other racial/ethnic populations needs to be understood before the loci can be used widely in risk modeling. In our study, we examined 82 previously reported risk variants in 4,853 prostate cancer cases and 4,678 controls of African ancestry. We performed association testing for each variant using logistic regression adjusted for age, study and global ancestry. Of the 82 known risk variants, 68 (83%) had effects that were directionally consistent in their association with prostate cancer risk and 30 (37%) were significantly associated with risk at p < 0.05, with the most statistically significant variants being rs116041037 (p = 3.7 × 10(-26) ) and rs6983561 (p = 1.1 × 10(-16) ) at 8q24, as well as rs7210100 (p = 5.4 × 10(-8) ) at 17q21. By exploring each locus in search of better markers, the number of variants that captured risk in men of African ancestry (p < 0.05) increased from 30 (37%) to 44 (54%). An aggregate score comprised of these 44 markers was strongly associated with prostate cancer risk [per-allele odds ratio (OR) = 1.12, p = 7.3 × 10(-98) ]. In summary, the consistent directions of effects for the vast majority of variants in men of African ancestry indicate common functional alleles that are shared across populations. Further exploration of these susceptibility loci is needed to identify the underlying biologically relevant variants to improve prostate cancer risk modeling in populations of African ancestry.

  View details for DOI 10.1002/ijc.29066

  View details for Web of Science ID 000346350500046

  View details for PubMedCentralID PMC4268262

• Relationship Between Male Pattern Baldness and the Risk of Aggressive Prostate Cancer: An Analysis of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial JOURNAL OF CLINICAL ONCOLOGY Zhou, C. K., Pfeiffer, R. M., Cleary, S. D., Hoffman, H. J., Levine, P. H., Chu, L. W., Hsing, A. W., Cook, M. B. 2015; 33 (5): 419-U63

  Abstract

  Male pattern baldness and prostate cancer appear to share common pathophysiologic mechanisms. However, results from previous studies that assess their relationship have been inconsistent. Therefore, we investigated the association of male pattern baldness at age 45 years with risks of overall and subtypes of prostate cancer in a large, prospective cohort—the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.We included 39,070 men from the usual care and screening arms of the trial cohort who had no cancer diagnosis (excluding nonmelanoma skin cancer) at the start of follow-up and recalled their hair-loss patterns at age 45 years. Hazard ratios (HRs) and 95% CIs were estimated by using Cox proportional hazards regression models with age as the time metric.During follow-up (median, 2.78 years), 1,138 incident prostate cancer cases were diagnosed, 571 of which were aggressive (biopsy Gleason score ≥ 7, and/or clinical stage III or greater, and/or fatal). Compared with no baldness, frontal plus moderate vertex baldness at age 45 years was not significantly associated with overall (HR, 1.19; 95% CI, 0.98 to 1.45) or nonaggressive (HR, 0.97; 95% CI, 0.72 to 1.30) prostate cancer risk but was significantly associated with increased risk of aggressive prostate cancer (HR, 1.39; 95% CI, 1.07 to 1.80). Adjustment for covariates did not substantially alter these estimates. Other classes of baldness were not significantly associated with overall or subtypes of prostate cancer.Our analysis indicates that frontal plus moderate vertex baldness at age 45 years is associated with an increased risk of aggressive prostate cancer and supports the possibility of common pathophysiologic mechanisms.

  View details for DOI 10.1200/JCO.2014.55.4279

  View details for Web of Science ID 000352458200011

  View details for PubMedID 25225425

• Methodological Considerations in Estimation of Phenotype Heritability Using Genome-Wide SNP Data, Illustrated by an Analysis of the Heritability of Height in a Large Sample of African Ancestry Adults. PloS one Chen, F., He, J., Zhang, J., Chen, G. K., Thomas, V., Ambrosone, C. B., Bandera, E. V., Berndt, S. I., Bernstein, L., Blot, W. J., Cai, Q., Carpten, J., Casey, G., Chanock, S. J., Cheng, I., Chu, L., Deming, S. L., Driver, W. R., Goodman, P., Hayes, R. B., Hennis, A. J., Hsing, A. W., Hu, J. J., Ingles, S. A., John, E. M., Kittles, R. A., Kolb, S., Leske, M. C., Millikan, R. C., Monroe, K. R., Murphy, A., Nemesure, B., Neslund-Dudas, C., Nyante, S., Ostrander, E. A., Press, M. F., Rodriguez-Gil, J. L., Rybicki, B. A., Schumacher, F., Stanford, J. L., Signorello, L. B., Strom, S. S., Stevens, V., Van Den Berg, D., Wang, Z., Witte, J. S., Wu, S., Yamamura, Y., Zheng, W., Ziegler, R. G., Stram, A. H., Kolonel, L. N., Le Marchand, L., Henderson, B. E., Haiman, C. A., Stram, D. O. 2015; 10 (6)

  Abstract

  Height has an extremely polygenic pattern of inheritance. Genome-wide association studies (GWAS) have revealed hundreds of common variants that are associated with human height at genome-wide levels of significance. However, only a small fraction of phenotypic variation can be explained by the aggregate of these common variants. In a large study of African-American men and women (n = 14,419), we genotyped and analyzed 966,578 autosomal SNPs across the entire genome using a linear mixed model variance components approach implemented in the program GCTA (Yang et al Nat Genet 2010), and estimated an additive heritability of 44.7% (se: 3.7%) for this phenotype in a sample of evidently unrelated individuals. While this estimated value is similar to that given by Yang et al in their analyses, we remain concerned about two related issues: (1) whether in the complete absence of hidden relatedness, variance components methods have adequate power to estimate heritability when a very large number of SNPs are used in the analysis; and (2) whether estimation of heritability may be biased, in real studies, by low levels of residual hidden relatedness. We addressed the first question in a semi-analytic fashion by directly simulating the distribution of the score statistic for a test of zero heritability with and without low levels of relatedness. The second question was addressed by a very careful comparison of the behavior of estimated heritability for both observed (self-reported) height and simulated phenotypes compared to imputation R2 as a function of the number of SNPs used in the analysis. These simulations help to address the important question about whether today's GWAS SNPs will remain useful for imputing causal variants that are discovered using very large sample sizes in future studies of height, or whether the causal variants themselves will need to be genotyped de novo in order to build a prediction model that ultimately captures a large fraction of the variability of height, and by implication other complex phenotypes. Our overall conclusions are that when study sizes are quite large (5,000 or so) the additive heritability estimate for height is not apparently biased upwards using the linear mixed model; however there is evidence in our simulation that a very large number of causal variants (many thousands) each with very small effect on phenotypic variance will need to be discovered to fill the gap between the heritability explained by known versus unknown causal variants. We conclude that today's GWAS data will remain useful in the future for causal variant prediction, but that finding the causal variants that need to be predicted may be extremely laborious.

  View details for DOI 10.1371/journal.pone.0131106

  View details for PubMedID 26125186

• Finasteride concentrations and prostate cancer risk: results from the Prostate Cancer Prevention Trial. PloS one Chau, C. H., Price, D. K., Till, C., Goodman, P. J., Chen, X., Leach, R. J., Johnson-Pais, T. L., Hsing, A. W., Hoque, A., Tangen, C. M., Chu, L., Parnes, H. L., Schenk, J. M., Reichardt, J. K., Thompson, I. M., Figg, W. D. 2015; 10 (5)

  Abstract

  In the Prostate Cancer Prevention Trial (PCPT), finasteride reduced the risk of prostate cancer by 25%, even though high-grade prostate cancer was more common in the finasteride group. However, it remains to be determined whether finasteride concentrations may affect prostate cancer risk. In this study, we examined the association between serum finasteride concentrations and the risk of prostate cancer in the treatment arm of the PCPT and determined factors involved in modifying drug concentrations.Data for this nested case-control study are from the PCPT. Cases were drawn from men with biopsy-proven prostate cancer and matched controls. Finasteride concentrations were measured using a liquid chromatography-mass spectrometry validated assay. The association of serum finasteride concentrations with prostate cancer risk was determined by logistic regression. We also examine whether polymorphisms in the enzyme target and metabolism genes of finasteride are related to drug concentrations using linear regression.Among men with detectable finasteride concentrations, there was no association between finasteride concentrations and prostate cancer risk, low-grade or high-grade, when finasteride concentration was analyzed as a continuous variable or categorized by cutoff points. Since there was no concentration-dependent effect on prostate cancer, any exposure to finasteride intake may reduce prostate cancer risk. Of the twenty-seven SNPs assessed in the enzyme target and metabolism pathway, five SNPs in two genes, CYP3A4 (rs2242480; rs4646437; rs4986910), and CYP3A5 (rs15524; rs776746) were significantly associated with modifying finasteride concentrations. These results suggest that finasteride exposure may reduce prostate cancer risk and finasteride concentrations are affected by genetic variations in genes responsible for altering its metabolism pathway.ClinicalTrials.gov NCT00288106.

  View details for DOI 10.1371/journal.pone.0126672

  View details for PubMedID 25955319

• Prospective study of human herpesvirus type 8 serostatus and prostate cancer risk in the placebo arm of the Prostate Cancer Prevention Trial CANCER CAUSES & CONTROL Sutcliffe, S., Till, C., Jenkins, F. J., Gaydos, C. A., Goodman, P. J., Hoque, A. M., Hsing, A. W., Thompson, I. M., Nelson, W. G., De Marzo, A. M., Platz, E. A. 2015; 26 (1): 35-44

  Abstract

  Human herpesvirus type 8 (HHV-8), a gamma herpesvirus associated with Kaposi's sarcoma, has been proposed as a candidate risk factor for prostate cancer (PCa) because of its detection in benign and malignant prostate specimens, and its relation with histologic prostatic inflammation. We investigated the possible relation between pre-diagnostic HHV-8 infection and PCa risk in a case-control study sampled from the placebo arm of the Prostate Cancer Prevention Trial.We defined cases as men with a confirmed diagnosis of PCa after visit 2 (n = 315) and controls as men not diagnosed with PCa during the trial who also had a negative end-of-study prostate biopsy (n = 315). We tested sera from visit 2 for IgG antibodies against HHV-8 using a monoclonal antibody-enhanced immunofluorescence assay against multiple lytic HHV-8 antigens.The adjusted seroprevalence of HHV-8 infection was 11.6 % for cases and 11.0 % for controls (p = 0.81). No association was observed between HHV-8 seropositivity and PCa risk (OR 1.06, 95 % CI 0.65-1.76).Our findings of a null association between HHV-8 seropositivity and PCa risk do not support an association between HHV-8 infection and PCa development, consistent with the general tendency of the epidemiologic literature to date.

  View details for DOI 10.1007/s10552-014-0480-5

  View details for Web of Science ID 000347281800004

  View details for PubMedCentralID PMC4282945

• Non-Steroidal Anti-Inflammatory Drugs Use Is Associated with Reduced Risk of Inflammation-Associated Cancers: NIH-AARP Study PLOS ONE Shebl, F. M., Hsing, A. W., Park, Y., Hollenbeck, A. R., Chu, L. W., Meyer, T. E., Koshiol, J. 2014; 9 (12)

  View details for DOI 10.1371/journal.pone.0114633

  View details for Web of Science ID 000347119100013

• Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33. Human molecular genetics Wang, Z., Zhu, B., Zhang, M., Parikh, H., Jia, J., Chung, C. C., Sampson, J. N., Hoskins, J. W., Hutchinson, A., Burdette, L., Ibrahim, A., Hautman, C., Raj, P. S., Abnet, C. C., Adjei, A. A., Ahlbom, A., Albanes, D., Allen, N. E., Ambrosone, C. B., Aldrich, M., Amiano, P., Amos, C., Andersson, U., Andriole, G., Andrulis, I. L., Arici, C., Arslan, A. A., Austin, M. A., Baris, D., Barkauskas, D. A., Bassig, B. A., Beane Freeman, L. E., Berg, C. D., Berndt, S. I., Bertazzi, P. A., Biritwum, R. B., Black, A., Blot, W., Boeing, H., Boffetta, P., Bolton, K., Boutron-Ruault, M., Bracci, P. M., Brennan, P., Brinton, L. A., Brotzman, M., Bueno-de-Mesquita, H. B., Buring, J. E., Butler, M. A., Cai, Q., Cancel-Tassin, G., Canzian, F., Cao, G., Caporaso, N. E., Carrato, A., Carreon, T., Carta, A., Chang, G., Chang, I., Chang-Claude, J., Che, X., Chen, C., Chen, C., Chen, C., Chen, C., Chen, K., Chen, Y., Chokkalingam, A. P., Chu, L. W., Clavel-Chapelon, F., Colditz, G. A., Colt, J. S., Conti, D., Cook, M. B., Cortessis, V. K., Crawford, E. D., Cussenot, O., Davis, F. G., De Vivo, I., Deng, X., Ding, T., Dinney, C. P., Di Stefano, A. L., Diver, W. R., Duell, E. J., Elena, J. W., Fan, J., Feigelson, H. S., Feychting, M., Figueroa, J. D., Flanagan, A. M., Fraumeni, J. F., Freedman, N. D., Fridley, B. L., Fuchs, C. S., Gago-Dominguez, M., Gallinger, S., Gao, Y., Gapstur, S. M., Garcia-Closas, M., Garcia-Closas, R., Gastier-Foster, J. M., Gaziano, J. M., Gerhard, D. S., Giffen, C. A., Giles, G. G., Gillanders, E. M., Giovannucci, E. L., Goggins, M., Gokgoz, N., Goldstein, A. M., Gonzalez, C., Gorlick, R., Greene, M. H., Gross, M., Grossman, H. B., Grubb, R., Gu, J., Guan, P., Haiman, C. A., Hallmans, G., Hankinson, S. E., Harris, C. C., Hartge, P., Hattinger, C., Hayes, R. B., He, Q., Helman, L., Henderson, B. E., Henriksson, R., Hoffman-Bolton, J., Hohensee, C., Holly, E. A., Hong, Y., Hoover, R. N., Hosgood, H. D., Hsiao, C., Hsing, A. W., Hsiung, C. A., Hu, N., Hu, W., Hu, Z., Huang, M., Hunter, D. J., Inskip, P. D., Ito, H., Jacobs, E. J., Jacobs, K. B., Jenab, M., Ji, B., Johansen, C., Johansson, M., Johnson, A., Kaaks, R., Kamat, A. M., Kamineni, A., Karagas, M., Khanna, C., Khaw, K., Kim, C., Kim, I., Kim, J. H., Kim, Y. H., Kim, Y., Kim, Y. T., Kang, C. H., Jung, Y. J., Kitahara, C. M., Klein, A. P., Klein, R., Kogevinas, M., Koh, W., Kohno, T., Kolonel, L. N., Kooperberg, C., Kratz, C. P., Krogh, V., Kunitoh, H., Kurtz, R. C., Kurucu, N., Lan, Q., Lathrop, M., Lau, C. C., Lecanda, F., Lee, K., Lee, M. P., Le Marchand, L., Lerner, S. P., Li, D., Liao, L. M., Lim, W., Lin, D., Lin, J., Lindstrom, S., Linet, M. S., Lissowska, J., Liu, J., Ljungberg, B., Lloreta, J., Lu, D., Ma, J., Malats, N., Mannisto, S., Marina, N., Mastrangelo, G., Matsuo, K., McGlynn, K. A., McKean-Cowdin, R., McNeill, L. H., Mcwilliams, R. R., Melin, B. S., Meltzer, P. S., Mensah, J. E., Miao, X., Michaud, D. S., Mondul, A. M., Moore, L. E., Muir, K., Niwa, S., Olson, S. H., Orr, N., Panico, S., Park, J. Y., Patel, A. V., Patino-Garcia, A., Pavanello, S., Peeters, P. H., Peplonska, B., Peters, U., Petersen, G. M., Picci, P., Pike, M. C., Porru, S., Prescott, J., Pu, X., Purdue, M. P., Qiao, Y., Rajaraman, P., Riboli, E., Risch, H. A., Rodabough, R. J., Rothman, N., Ruder, A. M., Ryu, J., Sanson, M., Schned, A., Schumacher, F. R., Schwartz, A. G., Schwartz, K. L., Schwenn, M., Scotlandi, K., Seow, A., Serra, C., Serra, M., Sesso, H. D., Severi, G., Shen, H., Shen, M., Shete, S., Shiraishi, K., Shu, X., Siddiq, A., Sierrasesumaga, L., Sierri, S., Loon Sihoe, A. D., Silverman, D. T., Simon, M., Southey, M. C., Spector, L., Spitz, M., Stampfer, M., Stattin, P., Stern, M. C., Stevens, V. L., Stolzenberg-Solomon, R. Z., Stram, D. O., Strom, S. S., Su, W., Sund, M., Sung, S. W., Swerdlow, A., Tan, W., Tanaka, H., Tang, W., Tang, Z., Tardon, A., Tay, E., Taylor, P. R., Tettey, Y., Thomas, D. M., Tirabosco, R., Tjonneland, A., Tobias, G. S., Toro, J. R., Travis, R. C., Trichopoulos, D., Troisi, R., Truelove, A., Tsai, Y., Tucker, M. A., Tumino, R., Van Den Berg, D., Van Den Eeden, S. K., Vermeulen, R., Vineis, P., Visvanathan, K., Vogel, U., Wang, C., Wang, C., Wang, J., Wang, S. S., Weiderpass, E., Weinstein, S. J., Wentzensen, N., Wheeler, W., White, E., Wiencke, J. K., Wolk, A., Wolpin, B. M., Wong, M. P., Wrensch, M., Wu, C., Wu, T., Wu, X., Wu, Y., Wunder, J. S., Xiang, Y., Xu, J., Yang, H. P., Yang, P., Yatabe, Y., Ye, Y., Yeboah, E. D., Yin, Z., Ying, C., Yu, C., Yu, K., Yuan, J., Zanetti, K. A., Zeleniuch-Jacquotte, A., Zheng, W., Zhou, B., Mirabello, L., Savage, S. A., Kraft, P., Chanock, S. J., Yeager, M., Landi, M. T., Shi, J., Chatterjee, N., Amundadottir, L. T. 2014; 23 (24): 6616-6633

  Abstract

  Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.

  View details for DOI 10.1093/hmg/ddu363

  View details for PubMedID 25027329

• Variants in motilin, somatostatin and their receptor genes and risk of biliary tract cancers and stones in Shanghai, China. Meta gene Xu, H., Hsing, A. W., Koshiol, J., Chu, L. W., Cheng, J., Gao, J., Tan, Y., Wang, B., Shen, M., Gao, Y. 2014; 2: 418-426

  Abstract

  Altered motility of the gallbladder can result in gallstone and cholecystitis, which are important risk factor for biliary tract cancer. Motilin (MLN) and somatostatin (SST) are known important modulators of gallbladder motility. To determine whether genetic variants in motilin, somatostatin, and their receptor genes are associated with the risk of biliary tract cancers and stones, nine tag-SNPs were determined in 439 biliary tract cancer cases (253 gallbladder, 133 extrahepatic bile duct and 53 ampulla of Vater cancer cases), 429 biliary stone cases, and 447 population controls in a population-based case-control study in Shanghai, China. We found that subjects with the MLNR rs9568169 AA genotype and SSTR5 rs169068 CC genotype were significantly associated with risk of extrahepatic bile duct cancer (OR =0.49, 95% CI: 0.27-0.89; OR =2.40, 95% CI: 1.13-5.13) compared to the major genotypes. MLN rs2281820 CT and rs3793079 AT genotypes had significantly increased risks of gallstones (OR =1.52, 95% CI: 1.06-2.18; OR =1.64, 95% CI: 1.20-2.25) compared to TT genotypes. Besides, Haplotype analysis showed that MLN T-T-T haplotype (rs2281820-rs3793079-rs2281819) had a non-significantly elevated risk of gallstone (OR =1.30, 95% CI: 0.91-1.86) compared with C-A-A haplotype. To the best of our knowledge, this is the first study to report an association between genetic polymorphisms in MLN, MLNR and their receptor genes and risk of biliary tract cancers and stones.

  View details for PubMedID 24999450

  View details for PubMedCentralID PMC4080205

• Leveraging population admixture to characterize the heritability of complex traits NATURE GENETICS Zaitlen, N., Pasaniuc, B., Sankararaman, S., Bhatia, G., Zhang, J., Gusev, A., Young, T., Tandon, A., Pollack, S., Vilhjalmsson, B. J., Assimes, T. L., Berndt, S. I., Blot, W. J., Chanock, S., Franceschini, N., Goodman, P. G., He, J., Hennis, A. J., Hsing, A., Ingles, S. A., Isaacs, W., Kittles, R. A., Klein, E. A., Lange, L. A., Nemesure, B., Patterson, N., Reich, D., Rybicki, B. A., Stanford, J. L., Stevens, V. L., Strom, S. S., Whitse, E. A., Witte, J. S., Xu, J., Haiman, C., Wilson, J. G., Kooperberg, C., Stram, D., Reiner, A. P., Tang, H., Price, A. L. 2014; 46 (12): 1356-1362

  View details for DOI 10.1038/ng.3139

  View details for Web of Science ID 000345547300019

• Leveraging population admixture to characterize the heritability of complex traits. Nature genetics Zaitlen, N., Pasaniuc, B., Sankararaman, S., Bhatia, G., Zhang, J., Gusev, A., Young, T., Tandon, A., Pollack, S., Vilhjálmsson, B. J., Assimes, T. L., Berndt, S. I., Blot, W. J., Chanock, S., Franceschini, N., Goodman, P. G., He, J., Hennis, A. J., Hsing, A., Ingles, S. A., Isaacs, W., Kittles, R. A., Klein, E. A., Lange, L. A., Nemesure, B., Patterson, N., Reich, D., Rybicki, B. A., Stanford, J. L., Stevens, V. L., Strom, S. S., Whitsel, E. A., Witte, J. S., Xu, J., Haiman, C., Wilson, J. G., Kooperberg, C., Stram, D., Reiner, A. P., Tang, H., Price, A. L. 2014; 46 (12): 1356-1362

  Abstract

  Despite recent progress on estimating the heritability explained by genotyped SNPs (h(2)g), a large gap between h(2)g and estimates of total narrow-sense heritability (h(2)) remains. Explanations for this gap include rare variants or upward bias in family-based estimates of h(2) due to shared environment or epistasis. We estimate h(2) from unrelated individuals in admixed populations by first estimating the heritability explained by local ancestry (h(2)γ). We show that h(2)γ = 2FSTCθ(1 - θ)h(2), where FSTC measures frequency differences between populations at causal loci and θ is the genome-wide ancestry proportion. Our approach is not susceptible to biases caused by epistasis or shared environment. We applied this approach to the analysis of 13 phenotypes in 21,497 African-American individuals from 3 cohorts. For height and body mass index (BMI), we obtained h(2) estimates of 0.55 ± 0.09 and 0.23 ± 0.06, respectively, which are larger than estimates of h(2)g in these and other data but smaller than family-based estimates of h(2).

  View details for DOI 10.1038/ng.3139

  View details for PubMedID 25383972

  View details for PubMedCentralID PMC4244251

• Sex Steroid Hormone Metabolism in Relation to Risk of Aggressive Prostate Cancer CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Black, A., Pinsky, P. F., Grubb, R. L., Falk, R. T., Hsing, A. W., Chu, L., Meyer, T., Veenstra, T. D., Xu, X., Yu, K., Ziegler, R. G., Brinton, L. A., Hoover, R. N., Cook, M. B. 2014; 23 (11): 2374-2382

  Abstract

  The combined action of androgens and estrogens-specifically their balance-may play a role in prostate carcinogenesis, but existing evidence is sparse and inconsistent. We investigated associations between serum sex steroid hormones, including estrogen metabolites, and risk of aggressive prostate cancer.In a case-control study nested within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial cohort, we measured serum estrone, estradiol, and 13 estrogen metabolites, in the 2-, 4-, or 16-hydroxylation pathways, using an LC/MS-MS assay. Cases (n = 195) were non-Hispanic white men ages 55 to 70 years when diagnosed with aggressive prostate cancer (stage III or IV and/or Gleason ≥7). Controls (n = 195) were non-Hispanic white men without prostate cancer who were frequency matched to cases by age and year at blood draw, and time since baseline screen. Only men with serum testosterone and sex hormone-binding globulin measured previously were eligible. Logistic regression models were used to estimate ORs and 95% confidence intervals (95% CI).Risk of aggressive prostate cancer was strongly inversely associated with estradiol:testosterone ratio (OR4th quartile vs. 1st = 0.27; 95% CI, 0.12-0.59, Ptrend = 0.003) and positively associated with 2:16α-hydroxyestrone ratio (OR4th quartile vs. 1st = 2.44; 95% CI, 1.34-4.45, Ptrend = 0.001). Individual estrogen metabolites were unrelated to risk.Our findings suggest that sex steroid hormones, specifically the estrogen-androgen balance, may be important in the development of aggressive prostate cancer.Improved understanding of the hormonal etiology of prostate cancer is critical for prevention and therapeutic interventions.

  View details for DOI 10.1158/1055-9965.EPI-14-0700

  View details for Web of Science ID 000345279600020

  View details for PubMedCentralID PMC4221438

• Cancer Research in Asian American, Native Hawaiian, and Pacific Islander Populations: Accelerating Cancer Knowledge by Acknowledging and Leveraging Heterogeneity CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Gomez, S. L., Glaser, S. L., Horn-Ross, P. L., Cheng, I., Quach, T., Clarke, C. A., Reynolds, P., Shariff-Marco, S., Yang, J., Lee, M. M., Satariano, W. A., Hsing, A. W. 2014; 23 (11): 2202-2205

  Abstract

  The Asian American, Native Hawaiian, and Pacific Islander population is large, growing, and extremely heterogeneous. Not only do they bear unique burdens of incidence and outcomes for certain cancer types, they exhibit substantial variability in cancer incidence and survival patterns across the ethnic groups. By acknowledging and leveraging this heterogeneity through investing in cancer research within these populations, we have a unique opportunity to accelerate the availability of useful and impactful cancer knowledge. See all the articles in this CEBP Focus section, "Cancer in Asian and Pacific Islander Populations." Cancer Epidemiol Biomarkers Prev; 23(11); 2202-5. ©2014 AACR.

  View details for DOI 10.1158/1055-9965.EPI-14-0624

  View details for Web of Science ID 000345279600001

• Cancer research in Asian American, Native Hawaiian, and Pacific Islander populations: accelerating cancer knowledge by acknowledging and leveraging heterogeneity. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology Gomez, S. L., Glaser, S. L., Horn-Ross, P. L., Cheng, I., Quach, T., Clarke, C. A., Reynolds, P., Shariff-Marco, S., Yang, J., Lee, M. M., Satariano, W. A., Hsing, A. W. 2014; 23 (11): 2202-2205

  Abstract

  The Asian American, Native Hawaiian, and Pacific Islander population is large, growing, and extremely heterogeneous. Not only do they bear unique burdens of incidence and outcomes for certain cancer types, they exhibit substantial variability in cancer incidence and survival patterns across the ethnic groups. By acknowledging and leveraging this heterogeneity through investing in cancer research within these populations, we have a unique opportunity to accelerate the availability of useful and impactful cancer knowledge. See all the articles in this CEBP Focus section, "Cancer in Asian and Pacific Islander Populations." Cancer Epidemiol Biomarkers Prev; 23(11); 2202-5. ©2014 AACR.

  View details for DOI 10.1158/1055-9965.EPI-14-0624

  View details for PubMedID 25368394

• Sex steroid hormone metabolism in relation to risk of aggressive prostate cancer. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology Black, A., Pinsky, P. F., Grubb, R. L., Falk, R. T., Hsing, A. W., Chu, L., Meyer, T., Veenstra, T. D., Xu, X., Yu, K., Ziegler, R. G., Brinton, L. A., Hoover, R. N., Cook, M. B. 2014; 23 (11): 2374-2382

  Abstract

  The combined action of androgens and estrogens-specifically their balance-may play a role in prostate carcinogenesis, but existing evidence is sparse and inconsistent. We investigated associations between serum sex steroid hormones, including estrogen metabolites, and risk of aggressive prostate cancer.In a case-control study nested within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial cohort, we measured serum estrone, estradiol, and 13 estrogen metabolites, in the 2-, 4-, or 16-hydroxylation pathways, using an LC/MS-MS assay. Cases (n = 195) were non-Hispanic white men ages 55 to 70 years when diagnosed with aggressive prostate cancer (stage III or IV and/or Gleason ≥7). Controls (n = 195) were non-Hispanic white men without prostate cancer who were frequency matched to cases by age and year at blood draw, and time since baseline screen. Only men with serum testosterone and sex hormone-binding globulin measured previously were eligible. Logistic regression models were used to estimate ORs and 95% confidence intervals (95% CI).Risk of aggressive prostate cancer was strongly inversely associated with estradiol:testosterone ratio (OR4th quartile vs. 1st = 0.27; 95% CI, 0.12-0.59, Ptrend = 0.003) and positively associated with 2:16α-hydroxyestrone ratio (OR4th quartile vs. 1st = 2.44; 95% CI, 1.34-4.45, Ptrend = 0.001). Individual estrogen metabolites were unrelated to risk.Our findings suggest that sex steroid hormones, specifically the estrogen-androgen balance, may be important in the development of aggressive prostate cancer.Improved understanding of the hormonal etiology of prostate cancer is critical for prevention and therapeutic interventions.

  View details for DOI 10.1158/1055-9965.EPI-14-0700

  View details for PubMedID 25178985

• A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer NATURE GENETICS Al Olama, A. A., Kote-Jarai, Z., Berndt, S. I., Conti, D. V., Schumacher, F., Han, Y., Benlloch, S., Hazelett, D. J., Wang, Z., Saunders, E., Leongamornlert, D., Lindstrom, S., Jugurnauth-Little, S., Dadaev, T., Tymrakiewicz, M., Stram, D. O., Rand, K., Wan, P., Stram, A., Sheng, X., Pooler, L. C., Park, K., Xia, L., Tyrer, J., Kolonel, L. N., Le Marchand, L., Hoover, R. N., Machiela, M. J., Yeager, M., Burdette, L., Chung, C. C., Hutchinson, A., Yu, K., Goh, C., Ahmed, M., Govindasami, K., Guy, M., Tammela, T. L., Auvinen, A., Wahlfors, T., Schleutker, J., Visakorpi, T., Leinonen, K. A., Xu, J., Aly, M., Donovan, J., Travis, R. C., Key, T. J., Siddiq, A., Canzian, F., Khaw, K., Takahashi, A., Kubo, M., Pharoah, P., Pashayan, N., Weischer, M., Nordestgaard, B. G., Nielsen, S. F., Klarskov, P., Roder, M. A., Iversen, P., Thibodeau, S. N., McDonnell, S. K., Schaid, D. J., Stanford, J. L., Kolb, S., Holt, S., Knudsen, B., Coll, A. H., Gapstur, S. M., Diver, W. R., Stevens, V. L., Maier, C., Luedeke, M., Herkommer, K., Rinckleb, A. E., Strom, S. S., Pettaway, C., Yeboah, E. D., Tettey, Y., Biritwum, R. B., Adjei, A. A., Tay, E., Truelove, A., Niwa, S., Choklcalingam, A. P., Cannon-Albright, L., Cybulski, C., Wokolorczyk, D., Kluzniak, W., Park, J., Sellers, T., Lin, H., Isaacs, W. B., Partin, A. W., Brenner, H., Dieffenbach, A. K., Stegmaier, C., Chen, C., Giovannucci, E. L., Ma, J., Stampfer, M., Penney, K. L., Mucci, L., John, E. M., Ingles, S. A., Kittles, R. A., Murphy, A. B., Pandha, H., Michael, A., Kierzek, A. M., Blot, W., Signorello, L. B., Zheng, W., Albanes, D., Virtamo, J., Weinstein, S., Nemesure, B., Carpten, J., Leske, C., Wu, S., Hennis, A., Kibel, A. S., Rybicki, B. A., Neslund-Dudas, C., Hsing, A. W., Chu, L., Goodman, P. J., Klein, E. A., Zheng, S. L., Batra, J., Clements, J., Spurdle, A., Teixeira, M. R., Paulo, P., Maia, S., Slavov, C., Kaneva, R., Mitev, V., Witte, J. S., Casey, G., Gillanders, E. M., Seminara, D., Riboli, E., Hamdy, F. C., Coetzee, G. A., Li, Q., Freedman, M. L., Hunter, D. J., Muir, K., Gronberg, H., Nea, D. E., Southey, M., Giles, G. G., Severi, G., Cook, M. B., Nakagawa, H., Wiklund, F., Kraft, P., Chanock, S. J., Henderson, B. E., Easton, D. F., Eeles, R. A., Haiman, C. A. 2014; 46 (10): 1103-1109

  Abstract

  Genome-wide association studies (GWAS) have identified 76 variants associated with prostate cancer risk predominantly in populations of European ancestry. To identify additional susceptibility loci for this common cancer, we conducted a meta-analysis of > 10 million SNPs in 43,303 prostate cancer cases and 43,737 controls from studies in populations of European, African, Japanese and Latino ancestry. Twenty-three new susceptibility loci were identified at association P < 5 × 10(-8); 15 variants were identified among men of European ancestry, 7 were identified in multi-ancestry analyses and 1 was associated with early-onset prostate cancer. These 23 variants, in combination with known prostate cancer risk variants, explain 33% of the familial risk for this disease in European-ancestry populations. These findings provide new regions for investigation into the pathogenesis of prostate cancer and demonstrate the usefulness of combining ancestrally diverse populations to discover risk loci for disease.

  View details for DOI 10.1038/ng.3094

  View details for Web of Science ID 000342554100013

• A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer. Nature genetics Al Olama, A. A., Kote-Jarai, Z., Berndt, S. I., Conti, D. V., Schumacher, F., Han, Y., Benlloch, S., Hazelett, D. J., Wang, Z., Saunders, E., Leongamornlert, D., Lindstrom, S., Jugurnauth-Little, S., Dadaev, T., Tymrakiewicz, M., Stram, D. O., Rand, K., Wan, P., Stram, A., Sheng, X., Pooler, L. C., Park, K., Xia, L., Tyrer, J., Kolonel, L. N., Le Marchand, L., Hoover, R. N., Machiela, M. J., Yeager, M., Burdette, L., Chung, C. C., Hutchinson, A., Yu, K., Goh, C., Ahmed, M., Govindasami, K., Guy, M., Tammela, T. L., Auvinen, A., Wahlfors, T., Schleutker, J., Visakorpi, T., Leinonen, K. A., Xu, J., Aly, M., Donovan, J., Travis, R. C., Key, T. J., Siddiq, A., Canzian, F., Khaw, K., Takahashi, A., Kubo, M., Pharoah, P., Pashayan, N., Weischer, M., Nordestgaard, B. G., Nielsen, S. F., Klarskov, P., Røder, M. A., Iversen, P., Thibodeau, S. N., McDonnell, S. K., Schaid, D. J., Stanford, J. L., Kolb, S., Holt, S., Knudsen, B., Coll, A. H., Gapstur, S. M., Diver, W. R., Stevens, V. L., Maier, C., Luedeke, M., Herkommer, K., Rinckleb, A. E., Strom, S. S., Pettaway, C., Yeboah, E. D., Tettey, Y., Biritwum, R. B., Adjei, A. A., Tay, E., Truelove, A., Niwa, S., Chokkalingam, A. P., Cannon-Albright, L., Cybulski, C., Wokolorczyk, D., Kluzniak, W., Park, J., Sellers, T., Lin, H., Isaacs, W. B., Partin, A. W., Brenner, H., Dieffenbach, A. K., Stegmaier, C., Chen, C., Giovannucci, E. L., Ma, J., Stampfer, M., Penney, K. L., Mucci, L., John, E. M., Ingles, S. A., Kittles, R. A., Murphy, A. B., Pandha, H., Michael, A., Kierzek, A. M., Blot, W., Signorello, L. B., Zheng, W., Albanes, D., Virtamo, J., Weinstein, S., Nemesure, B., Carpten, J., Leske, C., Wu, S., Hennis, A., Kibel, A. S., Rybicki, B. A., Neslund-Dudas, C., Hsing, A. W., Chu, L., Goodman, P. J., Klein, E. A., Zheng, S. L., Batra, J., Clements, J., Spurdle, A., Teixeira, M. R., Paulo, P., Maia, S., Slavov, C., Kaneva, R., Mitev, V., Witte, J. S., Casey, G., Gillanders, E. M., Seminara, D., Riboli, E., Hamdy, F. C., Coetzee, G. A., Li, Q., Freedman, M. L., Hunter, D. J., Muir, K., Gronberg, H., Neal, D. E., Southey, M., Giles, G. G., Severi, G., Cook, M. B., Nakagawa, H., Wiklund, F., Kraft, P., Chanock, S. J., Henderson, B. E., Easton, D. F., Eeles, R. A., Haiman, C. A. 2014; 46 (10): 1103-1109

  Abstract

  Genome-wide association studies (GWAS) have identified 76 variants associated with prostate cancer risk predominantly in populations of European ancestry. To identify additional susceptibility loci for this common cancer, we conducted a meta-analysis of > 10 million SNPs in 43,303 prostate cancer cases and 43,737 controls from studies in populations of European, African, Japanese and Latino ancestry. Twenty-three new susceptibility loci were identified at association P < 5 × 10(-8); 15 variants were identified among men of European ancestry, 7 were identified in multi-ancestry analyses and 1 was associated with early-onset prostate cancer. These 23 variants, in combination with known prostate cancer risk variants, explain 33% of the familial risk for this disease in European-ancestry populations. These findings provide new regions for investigation into the pathogenesis of prostate cancer and demonstrate the usefulness of combining ancestrally diverse populations to discover risk loci for disease.

  View details for DOI 10.1038/ng.3094

  View details for PubMedID 25217961

• High Prevalence of Screen Detected Prostate Cancer in West Africans: Implications for Racial Disparity of Prostate Cancer JOURNAL OF UROLOGY Hsing, A. W., Yeboah, E., Biritwum, R., Tettey, Y., De Marzo, A. M., Adjei, A., Netto, G. J., Yu, K., Li, Y., Chokkalingam, A. P., Chu, L. W., Chia, D., Partin, A., Thompson, I. M., Quraishi, S. M., Niwa, S., Tarone, R., Hoover, R. N. 2014; 192 (3): 730-735

  Abstract

  To our knowledge the reasons for the high rates of prostate cancer in black American men are unknown. Genetic and lifestyle factors have been implicated. Better understanding of prostate cancer rates in West African men would help clarify why black American men have such high rates since the groups share genetic ancestry and yet have different lifestyles and screening practices. To estimate the prostate cancer burden in West African men we performed a population based screening study with biopsy confirmation in Ghana.We randomly selected 1,037 healthy men 50 to 74 years old from Accra, Ghana for prostate cancer screening with prostate specific antigen testing and digital rectal examination. Men with a positive screen result (positive digital rectal examination or prostate specific antigen greater than 2.5 ng/ml) underwent transrectal ultrasound guided biopsies.Of the 1,037 men 154 (14.9%) had a positive digital rectal examination and 272 (26.2%) had prostate specific antigen greater than 2.5 ng/ml, including 166 with prostate specific antigen greater than 4.0 ng/ml. A total of 352 men (33.9%) had a positive screen by prostate specific antigen or digital rectal examination and 307 (87%) underwent biopsy. Of these men 73 were confirmed to have prostate cancer, yielding a 7.0% screen detected prostate cancer prevalence (65 patients), including 5.8% with prostate specific antigen greater than 4.0 ng/ml.In this relatively unscreened population in Africa the screen detected prostate cancer prevalence is high, suggesting a possible role of genetics in prostate cancer etiology and the disparity in prostate cancer risk between black and white American men. Further studies are needed to confirm the high prostate cancer burden in African men and the role of genetics in prostate cancer etiology.

  View details for DOI 10.1016/j.juro.2014.04.017

  View details for Web of Science ID 000342105600028

  View details for PubMedCentralID PMC4332806

• High prevalence of screen detected prostate cancer in West Africans: implications for racial disparity of prostate cancer. journal of urology Hsing, A. W., Yeboah, E., Biritwum, R., Tettey, Y., De Marzo, A. M., Adjei, A., Netto, G. J., Yu, K., Li, Y., Chokkalingam, A. P., Chu, L. W., Chia, D., Partin, A., Thompson, I. M., Quraishi, S. M., Niwa, S., Tarone, R., Hoover, R. N. 2014; 192 (3): 730-735

  Abstract

  To our knowledge the reasons for the high rates of prostate cancer in black American men are unknown. Genetic and lifestyle factors have been implicated. Better understanding of prostate cancer rates in West African men would help clarify why black American men have such high rates since the groups share genetic ancestry and yet have different lifestyles and screening practices. To estimate the prostate cancer burden in West African men we performed a population based screening study with biopsy confirmation in Ghana.We randomly selected 1,037 healthy men 50 to 74 years old from Accra, Ghana for prostate cancer screening with prostate specific antigen testing and digital rectal examination. Men with a positive screen result (positive digital rectal examination or prostate specific antigen greater than 2.5 ng/ml) underwent transrectal ultrasound guided biopsies.Of the 1,037 men 154 (14.9%) had a positive digital rectal examination and 272 (26.2%) had prostate specific antigen greater than 2.5 ng/ml, including 166 with prostate specific antigen greater than 4.0 ng/ml. A total of 352 men (33.9%) had a positive screen by prostate specific antigen or digital rectal examination and 307 (87%) underwent biopsy. Of these men 73 were confirmed to have prostate cancer, yielding a 7.0% screen detected prostate cancer prevalence (65 patients), including 5.8% with prostate specific antigen greater than 4.0 ng/ml.In this relatively unscreened population in Africa the screen detected prostate cancer prevalence is high, suggesting a possible role of genetics in prostate cancer etiology and the disparity in prostate cancer risk between black and white American men. Further studies are needed to confirm the high prostate cancer burden in African men and the role of genetics in prostate cancer etiology.

  View details for DOI 10.1016/j.juro.2014.04.017

  View details for PubMedID 24747091

• Diabetes Mellitus and Risk of Thyroid Cancer: A Meta-Analysis PLOS ONE Yeo, Y., Ma, S., Hwang, Y., Horn-Ross, P. L., Hsing, A., Lee, K., Park, Y. J., Park, D., Yoo, K., Park, S. K. 2014; 9 (6)

  Abstract

  Diabetes mellitus (DM) is an important risk factor for endocrine cancers; however, the association with thyroid cancer is not clear. We performed a systematic review and meta-analysis to clarify the association between thyroid cancer and DM.We searched MEDLINE, PUBMED and EMBASE databases through July 2012, using search terms related to diabetes mellitus, cancer, and thyroid cancer. We conducted a meta-analysis of the risk of incidence of thyroid cancer from pre-existing diabetes. Of 2,123 titles initially identified, sixteen articles met our inclusion criteria. An additional article was identified from a bibliography. Totally, 14 cohort and 3 case-control studies were selected for the meta-analysis. The risks were estimated using random-effects model and sensitivity test for the studies which reported risk estimates and used different definition of DM.Compared with individuals without DM, the patients with DM were at 1.34-fold higher risk for thyroid cancer (95% CI 1.11-1.63). However, there was heterogeneity in the results (p<0.0001). Sensitivity tests and studies judged to be high quality did not show heterogeneity and DM was associated with higher risk for thyroid cancer in these sub-analyses (both of RRs = 1.18, 95% CIs 1.08-1.28). DM was associated with a 1.38-fold increased risk of thyroid cancer in women (95% CI 1.13-1.67) after sensitivity test. Risk of thyroid cancer in men did not remain significant (RR 1.11, 95% CI 0.80-1.53).Compared with their non-diabetic counterparts, women with pre-existing DM have an increased risk of thyroid cancer.

  View details for DOI 10.1371/journal.pone.0098135

  View details for Web of Science ID 000338278100012

  View details for PubMedID 24927125

• Insulin-like Growth Factor Pathway Genetic Polymorphisms, Circulating IGF1 and IGFBP3, and Prostate Cancer Survival JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE Cao, Y., Lindstroem, S., Schumacher, F., Stevens, V. L., Albanes, D., Berndt, S. I., Boeing, H., Bueno-de-Mesquita, H. B., Canzian, F., Chamosa, S., Chanock, S. J., Diver, W. R., Gapstur, S. M., Gaziano, J. M., Giovannucci, E. L., Haiman, C. A., Henderson, B., Johansson, M., Le Marchand, L., Palli, D., Rosner, B., Siddiq, A., Stampfer, M., Stram, D. O., Tamimi, R., Travis, R. C., Trichopoulos, D., Willett, W. C., Yeager, M., Kraft, P., Hsing, A. W., Pollak, M., Lin, X., Ma, J. 2014; 106 (6)

  Abstract

  The insulin-like growth factor (IGF) signaling pathway has been implicated in prostate cancer (PCa) initiation, but its role in progression remains unknown.Among 5887 PCa patients (704 PCa deaths) of European ancestry from seven cohorts in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium, we conducted Cox kernel machine pathway analysis to evaluate whether 530 tagging single nucleotide polymorphisms (SNPs) in 26 IGF pathway-related genes were collectively associated with PCa mortality. We also conducted SNP-specific analysis using stratified Cox models adjusting for multiple testing. In 2424 patients (313 PCa deaths), we evaluated the association of prediagnostic circulating IGF1 and IGFBP3 levels and PCa mortality. All statistical tests were two-sided.The IGF signaling pathway was associated with PCa mortality (P = .03), and IGF2-AS and SSTR2 were the main contributors (both P = .04). In SNP-specific analysis, 36 SNPs were associated with PCa mortality with P trend less than .05, but only three SNPs in the IGF2-AS remained statistically significant after gene-based corrections. Two were in linkage disequilibrium (r 2 = 1 for rs1004446 and rs3741211), whereas the third, rs4366464, was independent (r 2 = 0.03). The hazard ratios (HRs) per each additional risk allele were 1.19 (95% confidence interval [CI] = 1.06 to 1.34; P trend = .003) for rs3741211 and 1.44 (95% CI = 1.20 to 1.73; P trend < .001) for rs4366464. rs4366464 remained statistically significant after correction for all SNPs (P trend.corr = .04). Prediagnostic IGF1 (HRhighest vs lowest quartile = 0.71; 95% CI = 0.48 to 1.04) and IGFBP3 (HR = 0.93; 95% CI = 0.65 to 1.34) levels were not associated with PCa mortality.The IGF signaling pathway, primarily IGF2-AS and SSTR2 genes, may be important in PCa survival.

  View details for DOI 10.1093/jnci/dju085

  View details for Web of Science ID 000341636800003

  View details for PubMedCentralID PMC4081624

• Insulin-like Growth Factor Pathway Genetic Polymorphisms, Circulating IGF1 and IGFBP3, and Prostate Cancer Survival JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE Cao, Y., Lindstroem, S., Schumacher, F., Stevens, V. L., Albanes, D., Berndt, S. I., Boeing, H., Bueno-de-Mesquita, H. B., Canzian, F., Chamosa, S., Chanock, S. J., Diver, W. R., Gapstur, S. M., Gaziano, J. M., Giovannucci, E. L., Haiman, C. A., Henderson, B., Johansson, M., Le Marchand, L., Palli, D., Rosner, B., Siddiq, A., Stampfer, M., Stram, D. O., Tamimi, R., Travis, R. C., Trichopoulos, D., Willett, W. C., Yeager, M., Kraft, P., Hsing, A. W., Pollak, M., Lin, X., Ma, J. 2014; 106 (5)

  View details for DOI 10.1093/jnci/dju218

  View details for Web of Science ID 000341636100033

• A comprehensive resequence-analysis of 250 kb region of 8q24.21 in men of African ancestry PROSTATE Chung, C. C., Hsing, A. W., Yeboah, E., Biritwum, R., Tettey, Y., Adjei, A., Cook, M. B., De Marzo, A., Netto, G., Tay, E., Boland, J. F., Yeager, M., Chanock, S. J. 2014; 74 (6): 579-589

  Abstract

  Genome-wide association studies (GWAS) have identified that a ∼1 M region centromeric to the MYC oncogene on chromosome 8q24.21 harbors at least five independent loci associated with prostate cancer risk and additional loci associated with cancers of breast, colon, bladder, and chronic lymphocytic leukemia (CLL). Because GWAS identify genetic markers that may be indirectly associated with disease, fine-mapping based on sequence analysis provides important insights into patterns of linkage disequilibrium (LD) and is critical in defining the optimal variants to nominate for biological follow-up.To catalog variation in individuals of African ancestry, we resequenced a region (250 kb; chr8:128,050, 768–128, 300,801, hg19) containing several prostate cancer susceptibility loci as well as a locus associated with CLL. Our samples included 78 individuals from Ghana and 47 of African-Americans from Johns Hopkins University.After quality control metrics were applied to next-generation sequence data, 1,838 SNPs were identified. Of these, 285 were novel and not yet reported in any public database. Using genotypes derived from sequencing, we refined the LD and recombination hotspots within the region and determined a set of tag SNPs to be used in future fine-mapping studies. Based on LD, we annotated putative risk loci and their surrogates using ENCODE data, which should help guide laboratory studies.In comparison to the 1000 Genome Project data, we have identified additional variants that could be important in establishing priorities for future functional work designed to explain the biological basis of associations between SNPs and both prostate cancer and CLL.

  View details for DOI 10.1002/pros.22726

  View details for Web of Science ID 000333445500002

  View details for PubMedID 24783269

• A genome-wide association study of prostate cancer in West African men HUMAN GENETICS Cook, M. B., Wang, Z., Yeboah, E. D., Tettey, Y., Biritwum, R. B., Adjei, A. A., Tay, E., Truelove, A., Niwa, S., Chung, C. C., Chokkalingam, A. P., Chu, L. W., Yeager, M., Hutchinson, A., Yu, K., Rand, K. A., Haiman, C. A., Hoover, R. N., Hsing, A. W., Chanock, S. J. 2014; 133 (5): 509-521

  View details for DOI 10.1007/s00439-013-1387-z

  View details for Web of Science ID 000334519900004

• Anthropometric and Hormonal Risk Factors for Male Breast Cancer: Male Breast Cancer Pooling Project Results JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE Brinton, L. A., Cook, M. B., McCormack, V., Johnson, K. C., Olsson, H., Casagrande, J. T., Cooke, R., Falk, R. T., Gapstur, S. M., Gaudet, M. M., Gaziano, J. M., Gkiokas, G., Guenel, P., Henderson, B. E., Hollenbeck, A., Hsing, A. W., Kolonel, L. N., Isaacs, C., Lubin, J. H., Michels, K. B., Negri, E., Parisi, D., Petridou, E. T., Pike, M. C., Riboli, E., Sesso, H. D., Snyder, K., Swerdlow, A. J., Trichopoulos, D., Ursin, G., van den Brandt, P. A., Van Den Eeden, S. K., Weiderpass, E., Willett, W. C., Ewertz, M., Thomas, D. B. 2014; 106 (3)

  View details for DOI 10.1093/jnci/djt465

  View details for Web of Science ID 000334691200012

• Anthropometric and hormonal risk factors for male breast cancer: male breast cancer pooling project results. Journal of the National Cancer Institute Brinton, L. A., Cook, M. B., McCormack, V., Johnson, K. C., Olsson, H., Casagrande, J. T., Cooke, R., Falk, R. T., Gapstur, S. M., Gaudet, M. M., Gaziano, J. M., Gkiokas, G., Guénel, P., Henderson, B. E., Hollenbeck, A., Hsing, A. W., Kolonel, L. N., Isaacs, C., Lubin, J. H., Michels, K. B., Negri, E., Parisi, D., Petridou, E. T., Pike, M. C., Riboli, E., Sesso, H. D., Snyder, K., Swerdlow, A. J., Trichopoulos, D., Ursin, G., van den Brandt, P. A., Van Den Eeden, S. K., Weiderpass, E., Willett, W. C., Ewertz, M., Thomas, D. B. 2014; 106 (3): djt465-?

  Abstract

  The etiology of male breast cancer is poorly understood, partly because of its relative rarity. Although genetic factors are involved, less is known regarding the role of anthropometric and hormonally related risk factors.In the Male Breast Cancer Pooling Project, a consortium of 11 case-control and 10 cohort investigations involving 2405 case patients (n = 1190 from case-control and n = 1215 from cohort studies) and 52013 control subjects, individual participant data were harmonized and pooled. Unconditional logistic regression generated study design-specific (case-control/cohort) odds ratios (ORs) and 95% confidence intervals (CIs), with exposure estimates combined using fixed effects meta-analysis. All statistical tests were two-sided.Risk was statistically significantly associated with weight (highest/lowest tertile: OR = 1.36; 95% CI = 1.18 to 1.57), height (OR = 1.18; 95% CI = 1.01 to 1.38), and body mass index (BMI; OR = 1.30; 95% CI = 1.12 to 1.51), with evidence that recent rather than distant BMI was the strongest predictor. Klinefelter syndrome (OR = 24.7; 95% CI = 8.94 to 68.4) and gynecomastia (OR = 9.78; 95% CI = 7.52 to 12.7) were also statistically significantly associated with risk, relations that were independent of BMI. Diabetes also emerged as an independent risk factor (OR = 1.19; 95% CI = 1.04 to 1.37). There were also suggestive relations with cryptorchidism (OR = 2.18; 95% CI = 0.96 to 4.94) and orchitis (OR = 1.43; 95% CI = 1.02 to 1.99). Although age at onset of puberty and histories of infertility were unrelated to risk, never having had children was statistically significantly related (OR = 1.29; 95% CI = 1.01 to 1.66). Among individuals diagnosed at older ages, a history of fractures was statistically significantly related (OR = 1.41; 95% CI = 1.07 to 1.86).Consistent findings across case-control and cohort investigations, complemented by pooled analyses, indicated important roles for anthropometric and hormonal risk factors in the etiology of male breast cancer. Further investigation should focus on potential roles of endogenous hormones.

  View details for DOI 10.1093/jnci/djt465

  View details for PubMedID 24552677

  View details for PubMedCentralID PMC3975166

• Body mass index and mortality among blacks and whites adults in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial OBESITY Xiao, Q., Hsing, A. W., Park, Y., Moore, S. C., Matthews, C. E., de Gonzalez, A. B., Kitahara, C. M. 2014; 22 (1): 260-268

  Abstract

  In a large prospective cohort, we examined the relationship of body mass index (BMI) with mortality among blacks and compared the results to those among whites in this population.The study population consisted of 7,446 non-Hispanic black and 130,598 white participants, ages 49-78 at enrollment, in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. BMI at baseline, BMI at age 20, and BMI change were calculated using self-reported and recalled height and weight. Relative risks were stratified by race and sex and adjusted for age, education, marital status, and smoking.During follow-up, 1,495 black and 18,236 white participants died (mean = 13 years). Clear J-shaped associations between BMI and mortality were observed among white men and women. Among black men and women, the bottoms of these curves were flatter, and increasing risks of death with greater BMI were observed only at higher BMI levels (≥35.0). Associations for BMI at age 20 and BMI change also appeared to be stronger in magnitude in whites versus blacks, and these racial differences appeared to be more pronounced among women.Our results suggest that BMI may be more weakly associated with mortality in blacks, particularly black women, than in whites.

  View details for DOI 10.1002/oby.20412

  View details for Web of Science ID 000329613600038

  View details for PubMedID 23512729

• Non-steroidal anti-inflammatory drugs use is associated with reduced risk of inflammation-associated cancers: NIH-AARP study. PloS one Shebl, F. M., Hsing, A. W., Park, Y., Hollenbeck, A. R., Chu, L. W., Meyer, T. E., Koshiol, J. 2014; 9 (12)

  Abstract

  Chronic inflammation has been linked to cancers, and use of non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with reduced risk of several cancers. To further refine the magnitude of NSAID-related associations, in particular for cancers related to inflammation, such as alcohol-, infection-, obesity-, and smoking-related cancers, as well as for less common cancers, we evaluated the use of NSAIDs and cancer risk in a very large cohort. We used propensity scores to account for potential selection bias and hypothesized that NSAID use is associated with decreased cancer incidence.We conducted a prospective study among 314,522 participants in the NIH-AARP Diet and Health Study. Individuals who completed the lifestyle questionnaire, which included NSAID use, in 1996-1997 were followed through 2006. Information on cancer incidence was ascertained by linking to cancer registries and vital status databases.During 2,715,994 person-years of follow-up (median 10.1 person-years), there were 51,894 incident cancers. Compared with non-users of NSAIDs, individuals who reported use in the 12 months prior to interview had a significantly lower risk of all inflammation-related cancer, alcohol-related, infection-related, obesity-related, and smoking-related cancers [hazard ratio (HR) (95% CI)) 0.90 (0.87-0.93), 0.80 (0.74-0.85), 0.82 (0.78-0.87), 0.88 (0.84-0.92), and 0.88 (0.85-0.92) respectively)].After accounting for potential selection bias, our data showed an inverse association between NSAID use and alcohol-related, infection-related, obesity-related, and smoking-related cancers and support the hypothesis that inflammation is related to an increased risk of certain cancers.

  View details for DOI 10.1371/journal.pone.0114633

  View details for PubMedID 25551641

• Individual Variations in Serum Melatonin Levels through Time: Implications for Epidemiologic Studies PLOS ONE Nogueira, L. M., Sampson, J. N., Chu, L. W., Yu, K., Andriole, G., Church, T., Stanczyk, F. Z., Koshiol, J., Hsing, A. W. 2013; 8 (12)

  Abstract

  Melatonin, a marker for the circadian rhythm with serum levels peaking between 2AM and 5AM, is hypothesized to possess anti-cancer properties, making it a mechanistic candidate for the probable carcinogenic effect of circadian rhythm disruption. In order to weigh epidemiologic evidence on the association of melatonin with cancer, we must first understand the laboratory and biological sources of variability in melatonin levels measured in samples. Participants for this methodological study were men enrolled in the Prostate Lung Colorectal and Ovarian Cancer Screening Trial (PLCO). We measured serum melatonin levels over a five year period in 97 individuals to test if melatonin levels are steady over time. The Pearson correlation coefficient between two measures separated by 1 year was 0.87, while the correlation between two measures separated by 5 years was to 0.70. In an additional cross-sectional study of 292 individuals, we used Analysis of Variance to identify differences in melatonin levels between different lifestyle and environmental characteristics. Serum melatonin levels were slightly higher in samples collected from 130 individuals during the winter, (6.36±0.59 pg/ml) than in samples collected from 119 individuals during the summer (4.83±0.62 pg/ml). Serum melatonin levels were lowest in current smokers (3.02±1.25 pg/ml, p = 0.007) compared to never (6.66±0.66 pg/ml) and former (5.59±0.50 pg/ml) smokers whereas BMI did not significantly affect serum melatonin levels in this study. In conclusion, the high 5 year correlation of melatonin levels implies that single measurements may be used to detect population level associations between melatonin and risk of cancer. Furthermore, our results reiterate the need to record season of sample collection, and individual characteristics in order to maximize study power and prevent confounding.

  View details for DOI 10.1371/journal.pone.0083208

  View details for Web of Science ID 000328882000069

  View details for PubMedID 24376664

• Joint effects between five identified risk variants, allergy, and autoimmune conditions on glioma risk CANCER CAUSES & CONTROL Safaeian, M., Rajaraman, P., Hartge, P., Yeager, M., Linet, M., Butler, M. A., Ruder, A. M., Purdue, M. P., Hsing, A., Beane-Freeman, L., Hoppin, J. A., Albanes, D., Weinstein, S. J., Inskip, P. D., Brenner, A., Rothman, N., Chatterjee, N., Gillanders, E. M., Chanock, S. J., Wang, S. S. 2013; 24 (10): 1885-1891

  Abstract

  Common variants in two of the five genetic regions recently identified from genome-wide association studies (GWAS) of risk of glioma were reported to interact with a history of allergic symptoms. In a pooled analysis of five epidemiologic studies, we evaluated the association between the five GWAS implicated gene variants and allergies and autoimmune conditions (AIC) on glioma risk (851 adult glioma cases and 3,977 controls). We further evaluated the joint effects between allergies and AIC and these gene variants on glioma risk. Risk estimates were calculated as odds ratios (OR) and 95 % confidence intervals (95 % CI), adjusted for age, gender, and study. Joint effects were evaluated by conducting stratified analyses whereby the risk associations (OR and 95 % CI) with the allergy or autoimmune conditions for glioma were evaluated by the presence or absence of the 'at-risk' variant, and estimated p interaction by fitting models with the main effects of allergy or autoimmune conditions and genotype and an interaction (product) term between them. Four of the five SNPs previously reported by others were statistically significantly associated with increased risk of glioma in our study (rs2736100, rs4295627, rs4977756, and rs6010620); rs498872 was not associated with glioma in our study. Reporting any allergies or AIC was associated with reduced risks of glioma (allergy: adjusted OR = 0.71, 95 % CI 0.55-0.91; AIC: adjusted OR = 0.65, 95 % CI 0.47-0.90). We did not observe differential association between allergic or autoimmune conditions and glioma by genotype, and there were no statistically significant p interactions. Stratified analysis by glioma grade (low and high grade) did not suggest risk differences by disease grade. Our results do not provide evidence that allergies or AIC modulate the association between the four GWAS-identified SNPs examined and risk of glioma.

  View details for DOI 10.1007/s10552-013-0244-7

  View details for Web of Science ID 000324252500012

  View details for PubMedID 23903690

• Biliary tract cancer incidence in the United StatesDemographic and temporal variations by anatomic site INTERNATIONAL JOURNAL OF CANCER Castro, F. A., Koshiol, J., Hsing, A. W., Devesa, S. S. 2013; 133 (7): 1664-1671

  Abstract

  We evaluated incidence patterns of biliary tract cancers (gallbladder, extrahepatic bile duct, ampulla of Vater and not otherwise specified) to provide potential insight into the etiology of these cancers. Data were obtained from the population-based Surveillance, Epidemiology and End Results program. Rates for cases diagnosed during 1992-2009 were calculated by racial/ethnic, gender and age groups. Temporal trends during 1974-2009 and annual percentage changes (APC) during 1992-2009 were estimated. Age-adjusted rates by site were higher among American Indian/Alaska Natives, Hispanics (white) and Asian/Pacific Islanders (Asian/PI) and lower among whites and blacks. Gallbladder cancer was more common among women in all ethnic groups (female-to-male incidence rate ratio [IRR] ranged from 1.24 to 2.86), but bile duct and ampulla of Vater cancers were more common among men (female-to-male IRR 0.57 to 0.82). Gallbladder cancer rates declined among all racial/ethnic and gender groups except blacks (APC -0.4% to -3.9%). In contrast, extrahepatic bile duct cancer rates rose significantly in most female racial/ethnic groups; the APCs among whites were 0.8 among females and 1.3 among males, both significant. Rates for ampulla of Vater cancer decreased among Asian/PI females (APC -2.7%) but remained stable for the other groups. In addition to confirming that biliary tract cancer incidence patterns differ by gender and site and that the gallbladder cancer incidence rates have been declining, our study provides novel evidence that extrahepatic bile duct cancer rates are rising. These observations may help guide future etiologic studies.

  View details for DOI 10.1002/ijc.28161

  View details for Web of Science ID 000321762200015

  View details for PubMedID 23504585

• Prospective evaluation of serum sarcosine and risk of prostate cancer in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial CARCINOGENESIS Koutros, S., Meyer, T. E., Fox, S. D., Issaq, H. J., Veenstra, T. D., Huang, W., Yu, K., Albanes, D., Chu, L. W., Andriole, G., Hoover, R. N., Hsing, A. W., Berndt, S. I. 2013; 34 (10): 2281-2285

  Abstract

  Metabolomic profiling has identified, sarcosine, a derivative of the amino acid glycine, as an important metabolite involved in the etiology or natural history of prostate cancer. We examined the association between serum sarcosine levels and risk of prostate cancer in 1122 cases (813 non-aggressive and 309 aggressive) and 1112 controls in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Sarcosine was quantified using high-throughput liquid chromatography-mass spectrometry. A significantly increased risk of prostate cancer was observed with increasing levels of sarcosine (odds ratio [OR] for the highest quartile of exposure [Q4] versus the lowest quartile [Q1] = 1.30, 95% confidence interval [CI]: 1.02, 1.65; P-trend 0.03). When stratified by disease aggressiveness, we observed a stronger association for non-aggressive cases (OR for Q4 versus Q1 = 1.44, 95% CI: 1.11, 1.88; P-trend 0.006) but no association for aggressive prostate cancer (OR for Q4 versus Q1 = 1.03, 95% CI: 0.73, 1.47; P-trend 0.89). Although not statistically significant, temporal analyses showed a stronger association between sarcosine and prostate cancer for serum collected closer to diagnosis, suggesting that sarcosine may be an early biomarker of disease. Interestingly, the association between sarcosine and prostate cancer risk was stronger among men with diabetes (OR = 2.66, 95% CI: 1.04, 6.84) compared with those without reported diabetes (OR = 1.23, 95% CI: 0.95-1.59, P-interaction = 0.01). This study found that elevated levels of serum sarcosine are associated with an increased prostate cancer risk and evidence to suggest that sarcosine may be an early biomarker for this disease.

  View details for DOI 10.1093/carcin/bgt176

  View details for Web of Science ID 000325486200011

  View details for PubMedID 23698636

  View details for PubMedCentralID PMC3786375

• Variants in CCK and CCKAR genes to susceptibility to biliary tract cancers and stones: A population-based study in Shanghai, China JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY Xu, H., Hsing, A. W., Vogtmann, E., Chu, L. W., Cheng, J., Gao, J., Tan, Y., Wang, B., Shen, M., Gao, Y. 2013; 28 (9): 1476-1481

  Abstract

  Altered motility of the gallbladder is associated with an increased risk of gallstones and can result in biliary tract cancers. Cholecystokinin (CCK) is an important modulator of gallbladder motility which functions by activating CCK type-A receptor (CCKAR). The aim of this study was to determine whether genetic variants in CCK and CCKAR are associated with the risk of biliary tract cancers and stones.We investigated the associations between nine single nucleotide polymorphisms in CCK and CCKAR in a population-based case-control study, including 439 biliary tract cancer cases (253 gallbladder, 133 extrahepatic bile duct, and 53 ampulla of Vater cancer cases), 429 biliary stone cases, and 447 population controls in Shanghai, China.We found that women with the CCKAR rs1800855 AA genotype had an increased risk of gallbladder cancer (odds ratio = 2.37, 95% confidence interval (CI): 1.36-4.14) compared with subjects with the TT genotype, and remained significant after Bonferroni correction (P = 0.0056). Additionally, female carriers of the CCKAR haplotype C-T-C-T (rs2071011-rs915889-rs3822222-rs1800855) had a reduced risk of gallbladder cancer (odds ratio = 0.61, 95% confidence interval: 0.43-0.86) compared with those with the G-C-C-A haplotype; the association also remained significant after Bonferroni correction.These findings suggest that variants in the CCKAR gene may influence the risk of gallbladder cancer in women. Additional studies are needed to confirm our findings.

  View details for DOI 10.1111/jgh.12278

  View details for Web of Science ID 000323389700010

  View details for PubMedID 23701593

  View details for PubMedCentralID PMC3820582

• Evolution and Taxonomic Classification of Alphapapillomavirus 7 Complete Genomes: HPV18, HPV39, HPV45, HPV59, HPV68 and HPV70 PLOS ONE Chen, Z., Schiffman, M., Herrero, R., DeSalle, R., Anastos, K., Segondy, M., Sahasrabuddhe, V. V., Gravitt, P. E., Hsing, A. W., Burk, R. D. 2013; 8 (8)

  Abstract

  The species Alphapapillomavirus 7 (alpha-7) contains human papillomavirus genotypes that account for 15% of invasive cervical cancers and are disproportionately associated with adenocarcinoma of the cervix. Complete genome analyses enable identification and nomenclature of variant lineages and sublineages.The URR/E6 region was sequenced to screen for novel variants of HPV18, 39, 45, 59, 68, 70, 85 and 97 from 1147 cervical samples obtained from multiple geographic regions that had previously been shown to contain an alpha-7 HPV isolate. To study viral heterogeneity, the complete 8 kb genome of 128 isolates, including 109 sequenced for this analysis, were annotated and analyzed. Viral evolution was characterized by constructing phylogenic trees using maximum-likelihood and Bayesian algorithms. Global and pairwise alignments were used to calculate total and ORF/region nucleotide differences; lineages and sublineages were assigned using an alphanumeric system. The prototype genome was assigned to the A lineage or A1 sublineage.The genomic diversity of alpha-7 HPV types ranged from 1.1% to 6.7% nucleotide sequence differences; the extent of genome-genome pairwise intratype heterogeneity was 1.1% for HPV39, 1.3% for HPV59, 1.5% for HPV45, 1.6% for HPV70, 2.1% for HPV18, and 6.7% for HPV68. ME180 (previously a subtype of HPV68) was designated as the representative genome for HPV68 sublineage C1. Each ORF/region differed in sequence diversity, from most variable to least variable: noncoding region 1 (NCR1) / noncoding region 2 (NCR2) > upstream regulatory region (URR) > E6 / E7 > E2 / L2 > E1 / L1.These data provide estimates of the maximum viral genomic heterogeneity of alpha-7 HPV type variants. The proposed taxonomic system facilitates the comparison of variants across epidemiological and molecular studies. Sequence diversity, geographic distribution and phylogenetic topology of this clinically important group of HPVs suggest an independent evolutionary history for each type.

  View details for DOI 10.1371/journal.pone.0072565

  View details for Web of Science ID 000323570200075

  View details for PubMedID 23977318

• Known glioma risk loci are associated with glioma with a family history of brain tumours - A case-control gene association study INTERNATIONAL JOURNAL OF CANCER Melin, B., Dahlin, A. M., Andersson, U., Wang, Z., Henriksson, R., Hallmans, G., Bondy, M. L., Johansen, C., Feychting, M., Ahlbom, A., Kitahara, C. M., Wang, S. S., Ruder, A. M., Carreon, T., Butler, M. A., Inskip, P. D., Purdue, M., Hsing, A. W., Mechanic, L., Gillanders, E., Yeager, M., Linet, M., Chanock, S. J., Hartge, P., Rajaraman, P. 2013; 132 (10): 2464-2468

  Abstract

  Familial cancer can be used to leverage genetic association studies. Recent genome-wide association studies have reported independent associations between seven single nucleotide polymorphisms (SNPs) and risk of glioma. The aim of this study was to investigate whether glioma cases with a positive family history of brain tumours, defined as having at least one first- or second-degree relative with a history of brain tumour, are associated with known glioma risk loci. One thousand four hundred and thirty-one glioma cases and 2,868 cancer-free controls were identified from four case-control studies and two prospective cohorts from USA, Sweden and Denmark and genotyped for seven SNPs previously reported to be associated with glioma risk in case-control designed studies. Odds ratios were calculated by unconditional logistic regression. In analyses including glioma cases with a family history of brain tumours (n = 104) and control subjects free of glioma at baseline, three of seven SNPs were associated with glioma risk: rs2736100 (5p15.33, TERT), rs4977756 (9p21.3, CDKN2A-CDKN2B) and rs6010620 (20q13.33, RTEL1). After Bonferroni correction for multiple comparisons, only one marker was statistically significantly associated with glioma risk, rs6010620 (ORtrend for the minor (A) allele, 0.39; 95% CI: 0.25-0.61; Bonferroni adjusted ptrend , 1.7 × 10(-4) ). In conclusion, as previously shown for glioma regardless of family history of brain tumours, rs6010620 (RTEL1) was associated with an increased risk of glioma when restricting to cases with family history of brain tumours. These findings require confirmation in further studies with a larger number of glioma cases with a family history of brain tumours.

  View details for DOI 10.1002/ijc.27922

  View details for Web of Science ID 000315512300024

  View details for PubMedID 23115063

• A meta-analysis identifies new loci associated with body mass index in individuals of African ancestry. Nature genetics Monda, K. L., Chen, G. K., Taylor, K. C., Palmer, C., Edwards, T. L., Lange, L. A., Ng, M. C., Adeyemo, A. A., Allison, M. A., Bielak, L. F., Chen, G., Graff, M., Irvin, M. R., Rhie, S. K., Li, G., Liu, Y., Liu, Y., Lu, Y., Nalls, M. A., Sun, Y. V., Wojczynski, M. K., Yanek, L. R., Aldrich, M. C., Ademola, A., Amos, C. I., Bandera, E. V., Bock, C. H., Britton, A., Broeckel, U., Cai, Q., Caporaso, N. E., Carlson, C. S., Carpten, J., Casey, G., Chen, W., Chen, F., Chen, Y. I., Chiang, C. W., Coetzee, G. A., Demerath, E., Deming-Halverson, S. L., Driver, R. W., Dubbert, P., Feitosa, M. F., Feng, Y., Freedman, B. I., Gillanders, E. M., Gottesman, O., Guo, X., Haritunians, T., Harris, T., Harris, C. C., Hennis, A. J., Hernandez, D. G., McNeill, L. H., Howard, T. D., Howard, B. V., Howard, V. J., Johnson, K. C., Kang, S. J., Keating, B. J., Kolb, S., Kuller, L. H., Kutlar, A., Langefeld, C. D., Lettre, G., Lohman, K., Lotay, V., Lyon, H., Manson, J. E., Maixner, W., Meng, Y. A., Monroe, K. R., Morhason-Bello, I., Murphy, A. B., Mychaleckyj, J. C., Nadukuru, R., Nathanson, K. L., Nayak, U., N'Diaye, A., Nemesure, B., Wu, S., Leske, M. C., Neslund-Dudas, C., Neuhouser, M., Nyante, S., Ochs-Balcom, H., Ogunniyi, A., Ogundiran, T. O., Ojengbede, O., Olopade, O. I., Palmer, J. R., Ruiz-Narvaez, E. A., Palmer, N. D., Press, M. F., Rampersaud, E., Rasmussen-Torvik, L. J., Rodriguez-Gil, J. L., Salako, B., Schadt, E. E., Schwartz, A. G., Shriner, D. A., Siscovick, D., Smith, S. B., Wassertheil-Smoller, S., Speliotes, E. K., Spitz, M. R., Sucheston, L., Taylor, H., Tayo, B. O., Tucker, M. A., Van den Berg, D. J., Edwards, D. R., Wang, Z., Wiencke, J. K., Winkler, T. W., Witte, J. S., Wrensch, M., Wu, X., Yang, J. J., Levin, A. M., Young, T. R., Zakai, N. A., Cushman, M., Zanetti, K. A., Zhao, J. H., Zhao, W., Zheng, Y., Zhou, J., Ziegler, R. G., Zmuda, J. M., Fernandes, J. K., Gilkeson, G. S., Kamen, D. L., Hunt, K. J., Spruill, I. J., Ambrosone, C. B., Ambs, S., Arnett, D. K., Atwood, L., Becker, D. M., Berndt, S. I., Bernstein, L., Blot, W. J., Borecki, I. B., Bottinger, E. P., Bowden, D. W., Burke, G., Chanock, S. J., Cooper, R. S., Ding, J., Duggan, D., Evans, M. K., Fox, C., Garvey, W. T., Bradfield, J. P., Hakonarson, H., Grant, S. F., Hsing, A., Chu, L., Hu, J. J., Huo, D., Ingles, S. A., John, E. M., Jordan, J. M., Kabagambe, E. K., Kardia, S. L., Kittles, R. A., Goodman, P. J., Klein, E. A., Kolonel, L. N., Le Marchand, L., Liu, S., McKnight, B., Millikan, R. C., Mosley, T. H., Padhukasahasram, B., Williams, L. K., Patel, S. R., Peters, U., Pettaway, C. A., Peyser, P. A., Psaty, B. M., Redline, S., Rotimi, C. N., Rybicki, B. A., Sale, M. M., Schreiner, P. J., Signorello, L. B., Singleton, A. B., Stanford, J. L., Strom, S. S., Thun, M. J., Vitolins, M., Zheng, W., Moore, J. H., Williams, S. M., Ketkar, S., Zhu, X., Zonderman, A. B., Kooperberg, C., Papanicolaou, G. J., Henderson, B. E., Reiner, A. P., Hirschhorn, J. N., Loos, R. J., North, K. E., Haiman, C. A. 2013; 45 (6): 690-696

  Abstract

  Genome-wide association studies (GWAS) have identified 36 loci associated with body mass index (BMI), predominantly in populations of European ancestry. We conducted a meta-analysis to examine the association of >3.2 million SNPs with BMI in 39,144 men and women of African ancestry and followed up the most significant associations in an additional 32,268 individuals of African ancestry. We identified one new locus at 5q33 (GALNT10, rs7708584, P = 3.4 × 10(-11)) and another at 7p15 when we included data from the GIANT consortium (MIR148A-NFE2L3, rs10261878, P = 1.2 × 10(-10)). We also found suggestive evidence of an association at a third locus at 6q16 in the African-ancestry sample (KLHL32, rs974417, P = 6.9 × 10(-8)). Thirty-two of the 36 previously established BMI variants showed directionally consistent effect estimates in our GWAS (binomial P = 9.7 × 10(-7)), five of which reached genome-wide significance. These findings provide strong support for shared BMI loci across populations, as well as for the utility of studying ancestrally diverse populations.

  View details for DOI 10.1038/ng.2608

  View details for PubMedID 23583978

• Metabolomics in Epidemiology: Sources of Variability in Metabolite Measurements and Implications CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Sampson, J. N., Boca, S. M., Shu, X. O., Stolzenberg-Solomon, R. Z., Matthews, C. E., Hsing, A. W., Tan, Y. T., Ji, B., Chow, W., Cai, Q., Liu, D. K., Yang, G., Xiang, Y. B., Zheng, W., Sinha, R., Cross, A. J., Moore, S. C. 2013; 22 (4): 631-640

  Abstract

  Metabolite levels within an individual vary over time. This within-individual variability, coupled with technical variability, reduces the power for epidemiologic studies to detect associations with disease. Here, the authors assess the variability of a large subset of metabolites and evaluate the implications for epidemiologic studies.Using liquid chromatography/mass spectrometry (LC/MS) and gas chromatography-mass spectroscopy (GC/MS) platforms, 385 metabolites were measured in 60 women at baseline and year-one of the Shanghai Physical Activity Study, and observed patterns were confirmed in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening study.Although the authors found high technical reliability (median intraclass correlation = 0.8), reliability over time within an individual was low. Taken together, variability in the assay and variability within the individual accounted for the majority of variability for 64% of metabolites. Given this, a metabolite would need, on average, a relative risk of 3 (comparing upper and lower quartiles of "usual" levels) or 2 (comparing quartiles of observed levels) to be detected in 38%, 74%, and 97% of studies including 500, 1,000, and 5,000 individuals. Age, gender, and fasting status factors, which are often of less interest in epidemiologic studies, were associated with 30%, 67%, and 34% of metabolites, respectively, but the associations were weak and explained only a small proportion of the total metabolite variability.Metabolomics will require large, but feasible, sample sizes to detect the moderate effect sizes typical for epidemiologic studies.We offer guidelines for determining the sample sizes needed to conduct metabolomic studies in epidemiology.

  View details for DOI 10.1158/1055-9965.EPI-12-1109

  View details for Web of Science ID 000317960900020

  View details for PubMedID 23396963

  View details for PubMedCentralID PMC3617076

• Insulin-Like Growth Factors and Insulin-Like Growth Factor-Binding Proteins and Prostate Cancer Risk: Results from the Prostate Cancer Prevention Trial CANCER PREVENTION RESEARCH Neuhouser, M. L., Platz, E. A., Till, C., Tangen, C. M., Goodman, P. J., Kristal, A., Parnes, H. L., Tao, Y., Figg, W. D., Lucia, M. S., Hoque, A., Hsing, A. W., Thompson, I. M., Pollak, M. 2013; 6 (2): 91-99

  Abstract

  The role of the insulin-like growth factor (IGF) axis and whether IGFs interact with androgen-suppressing agents in relation to prostate carcinogenesis is unclear. This nested case-control study (n = 1,652 cases/1,543 controls) examined whether serum IGF1, IGF2, IGFBP2, IGFBP3, and the IGF1:IGFBP3 ratio were associated with prostate cancer in the Prostate Cancer Prevention Trial (PCPT), a randomized, placebo-controlled trial of finasteride for prostate cancer prevention. Presence or absence of cancer was determined by prostate biopsy. Baseline serum was assayed for IGF-axis analytes using ELISA. Logistic regression estimated ORs and 95% confidence intervals for risk of total, low-grade (Gleason 2-6) and high-grade (Gleason 7-10) cancers. Results were stratified by intervention assignment. In both the placebo and finasteride arms, serum IGF1, IGF2, IGFBP3, and the IGF1:IGFBP3 ratio were not associated with prostate cancer. However, men in the highest versus lowest quartile of serum IGFBP2 had a 48% (P(trend) = 0.02) and 55% (P(trend) = 0.01) increased risk for total and low-grade cancers, respectively. These IGFBP2 associations were attenuated and no longer statistically significant in the finasteride arm. Our results suggest that in general, serum IGF-axis analytes were not associated with prostate cancer risk in the PCPT in which presence or absence of all cancers was biopsy-determined. The exception was the finding that high serum IGFBP2 is a risk factor for low-grade disease, which was attenuated for men on finasteride. Further research is needed to understand better the risk incurred by high IGFBP2 and whether androgen-suppressing agents such as finasteride influence aspects of IGFBP2 physiology relevant to prostate carcinogenesis.

  View details for DOI 10.1158/1940-6207.CAPR-12-0250

  View details for Web of Science ID 000314676600004

  View details for PubMedID 23315596

• Global patterns of prostate cancer incidence, aggressiveness, and mortality in men of african descent. Prostate cancer Rebbeck, T. R., Devesa, S. S., Chang, B., Bunker, C. H., Cheng, I., Cooney, K., Eeles, R., Fernandez, P., Giri, V. N., Gueye, S. M., Haiman, C. A., Henderson, B. E., Heyns, C. F., Hu, J. J., Ingles, S. A., Isaacs, W., Jalloh, M., John, E. M., Kibel, A. S., Kidd, L. R., Layne, P., Leach, R. J., Neslund-Dudas, C., Okobia, M. N., Ostrander, E. A., Park, J. Y., Patrick, A. L., Phelan, C. M., Ragin, C., Roberts, R. A., Rybicki, B. A., Stanford, J. L., Strom, S., Thompson, I. M., Witte, J., Xu, J., Yeboah, E., Hsing, A. W., Zeigler-Johnson, C. M. 2013; 2013: 560857-?

  Abstract

  Prostate cancer (CaP) is the leading cancer among men of African descent in the USA, Caribbean, and Sub-Saharan Africa (SSA). The estimated number of CaP deaths in SSA during 2008 was more than five times that among African Americans and is expected to double in Africa by 2030. We summarize publicly available CaP data and collected data from the men of African descent and Carcinoma of the Prostate (MADCaP) Consortium and the African Caribbean Cancer Consortium (AC3) to evaluate CaP incidence and mortality in men of African descent worldwide. CaP incidence and mortality are highest in men of African descent in the USA and the Caribbean. Tumor stage and grade were highest in SSA. We report a higher proportion of T1 stage prostate tumors in countries with greater percent gross domestic product spent on health care and physicians per 100,000 persons. We also observed that regions with a higher proportion of advanced tumors reported lower mortality rates. This finding suggests that CaP is underdiagnosed and/or underreported in SSA men. Nonetheless, CaP incidence and mortality represent a significant public health problem in men of African descent around the world.

  View details for DOI 10.1155/2013/560857

  View details for PubMedID 23476788

  View details for PubMedCentralID PMC3583061

• Detectability and reproducibility of plasma levels of chemokines and soluble receptors. Results in immunology Agalliu, I., Xue, X., Cushman, M., Cornell, E., Hsing, A. W., Kaplan, R. C., Anastos, K., Rajpathak, S., Ho, G. Y. 2013; 3: 79-84

  Abstract

  Multiplex assays are available to measure an array of circulating chemokines, soluble cytokine receptors and growth factors. However, there is limited information regarding whether these analytes are suitable for large-scale epidemiological studies to assess their relationships with chronic diseases, including cancer.We examined detectability, assay repeatability, and 3-year within-subject reproducibility of plasma levels of 25 chemokines and 11 soluble receptors of cytokines and growth factors selected from the Human Millipore Panels. Plasma samples were obtained from 36 men (average age 62 years) and 17 women (average age 32 years) who participated in two epidemiological studies. Inter-assay and within-subject reproducibility were assessed by intraclass correlation coefficients (ICC).All analytes, except lymphotactin (47% detectability), were detectable in >90% of plasma samples. Inter-assay reproducibility for all analytes in 36 men tested three times on separate days were good to excellent (ICCs: 0.71-1.00). Within-subject reproducibility in 17 women sampled three times in three years were excellent (ICC ≥ 0.75) for five chemokines (eotaxin, fractalkine, 6Ckine, eotaxin 3, and SDF-1α+β) and three soluble receptors (sIL-1R2, sIL-4R and sVEGFR2); ICCs were fair to good (0.4 ≤ ICC < 0.75) for 15 chemokines and eight soluble receptors. However, five chemokines (GRO, IP-10, MIP-1β, BCA-1, and MIP-3α) had ICC < 0.4, suggesting biological variability.Multiplex assays for plasma levels of selected chemokines and soluble receptors showed good to excellent assay detectability and repeatability. Most analytes also had good 3-year within-subject reproducibility, indicating that a single measurement of these analytes may be used to assess biomarker-disease associations.

  View details for DOI 10.1016/j.rinim.2013.07.001

  View details for PubMedID 24600562

• Genome-wide association study in Chinese men identifies two new prostate cancer risk loci at 9q31.2 and 19q13.4 NATURE GENETICS Xu, J., Mo, Z., Ye, D., Wang, M., Liu, F., Jin, G., Xu, C., Wang, X., Shao, Q., Chen, Z., Tao, Z., Qi, J., Zhou, F., Wang, Z., Fu, Y., He, D., Wei, Q., Guo, J., Wu, D., Gao, X., Yuan, J., Wang, G., Xu, Y., Wang, G., Yao, H., Dong, P., Jiao, Y., Shen, M., Yang, J., Jun Ou-Yang, O. Y., Jiang, H., Zhu, Y., Ren, S., Zhang, Z., Yin, C., Gao, X., Dai, B., Hu, Z., Yang, Y., Wu, Q., Chen, H., Peng, P., Zheng, Y., Zheng, X., Xiang, Y., Long, J., Gong, J., Na, R., Lin, X., Yu, H., Wang, Z., Tao, S., Feng, J., Sun, J., Liu, W., Hsing, A., Rao, J., Ding, Q., Wiklund, F., Gronberg, H., Shu, X., Zheng, W., Shen, H., Jin, L., Shi, R., Lu, D., Zhang, X., Sun, J., Zheng, S. L., Sun, Y. 2012; 44 (11): 1231-1235

  Abstract

  Prostate cancer risk-associated variants have been reported in populations of European descent, African-Americans and Japanese using genome-wide association studies (GWAS). To systematically investigate prostate cancer risk-associated variants in Chinese men, we performed the first GWAS in Han Chinese. In addition to confirming several associations reported in other ancestry groups, this study identified two new risk-associated loci for prostate cancer on chromosomes 9q31.2 (rs817826, P = 5.45 × 10(-14)) and 19q13.4 (rs103294, P = 5.34 × 10(-16)) in 4,484 prostate cancer cases and 8,934 controls. The rs103294 marker at 19q13.4 is in strong linkage equilibrium with a 6.7-kb germline deletion that removes the first six of seven exons in LILRA3, a gene regulating inflammatory response, and was significantly associated with the mRNA expression of LILRA3 in T cells (P < 1 × 10(-4)). These findings may advance the understanding of genetic susceptibility to prostate cancer.

  View details for DOI 10.1038/ng.2424

  View details for Web of Science ID 000310495800015

  View details for PubMedID 23023329

• Associations of serum sex steroid hormone and 5a-androstane-3a,17ß-diol glucuronide concentrations with prostate cancer risk among men treated with finasteride. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology Kristal, A. R., Till, C., Tangen, C. M., Goodman, P. J., Neuhouser, M. L., Stanczyk, F. Z., Chu, L. W., Patel, S. K., Thompson, I. M., Reichardt, J. K., Hoque, A., Platz, E. A., Figg, W. D., van Bokhoven, A., Lippman, S. M., Hsing, A. W. 2012; 21 (10): 1823-1832

  Abstract

  Finasteride, an inhibitor of 5α-reductase (type II), lowers intraprostatic dihydrotestosterone (DHT), which is reflected in serum as reduced 5α-androstane-3α,17β-diol glucuronide (3α-dG). It also modestly increases serum testosterone (T), estrone (E(1)), and estradiol (E(2)). In this altered hormonal milieu, it is unknown whether serum concentrations of these hormones are associated with prostate cancer risk.In this nested case-control study of men in the finasteride arm of the Prostate Cancer Prevention Trial, sex steroid hormones and sex hormone binding globulin were measured at baseline and approximately 3-year posttreatment in 553 prostate cancer cases and 694 controls.Median posttreatment changes in concentrations of 3α-dG, T, E(1), and E(2) were -73.8%, +10.1%, +11.2%, and +7.5% (all P < 0.001), respectively. Neither the pre- nor posttreatment concentrations of 3α-dG, nor its change, were associated with risk. Pretreatment, high concentrations of E(1) and low concentrations of T were associated with increased cancer risk [OR; 95% confidence interval (CI) quartile 4 vs. 1: 1.38 (0.99-1.93) P(trend) = 0.03; 0.64 (0.43-0.93) P(trend) = 0.07, respectively]. Posttreatment, high concentrations of both E(1) and E(2) were associated with increased cancer risk [OR; 95% CI quartile 4 vs. 1: 1.54 (1.09-2.17) P(trend) = 0.03; 1.49 (1.07-2.07) P(trend) = 0.02, respectively].Among finasteride-treated men, concentrations of 3α-dG were not associated with total or Gleason grades 2 to 6, 7 to 10, or 8 to 10 cancer. High serum estrogens may increase cancer risk when intraprostatic DHT is pharmacologically lowered.Low posttreatment serum estrogens may identify men more likely to benefit from use of finasteride to prevent prostate cancer.

  View details for DOI 10.1158/1055-9965.EPI-12-0695

  View details for PubMedID 22879203

• Ovarian cancer and smoking: individual participant meta-analysis including 28 114 women with ovarian cancer from 51 epidemiological studies LANCET ONCOLOGY Beral, V., Gaitskell, K., Hermon, C., Moser, K., Reeves, G., Peto, R., Brinton, L., Marchbanks, P., Negri, E., Ness, R., Peeters, P. H., Vessey, M., Calle, E. E., Gapstur, S. M., Patel, A. V., Dal Maso, L., Talamini, R., Chetrit, A., Hirsh-Yechezkel, G., Lubin, F., Sadetzki, S., Banks, E., Beral, V., Bull, D., Callaghan, K., Crossley, B., Gaitskell, K., Goodill, A., Green, J., Hermon, C., Key, T., Moser, K., Reeves, G., Sitas, F., Collins, R., DOLL, R., Peto, R., Gonzalez, A., Lee, N., Marchbanks, P., Ory, H. W., Peterson, H. B., Wingo, P. A., Martin, N., PARDTHAISONG, T., SILPISORNKOSOL, S., Theetranont, C., BOOSIRI, B., CHUTIVONGSE, S., Jimakorn, P., Virutamasen, P., Wongsrichanalai, C., Tjonneland, A., Titus-Ernstoff, L., Byers, T., Rohan, T., Mosgaard, B. J., Vessey, M., Yeates, D., Freudenheim, J. L., Chang-Claude, J., Kaaks, R., Anderson, K. E., Folsom, A., Robien, K., Hampton, J., Newcomb, P. A., Rossing, M. A., Thomas, D. B., Weiss, N. S., Riboli, E., Clavel-Chapelon, F., Cramer, D., Hankinson, S. E., Tworoger, S. S., Franceschi, S., La Vecchia, C., Negri, E., Adami, H. O., Magnusson, C., Riman, T., Weiderpass, E., Wolk, A., Schouten, L. J., van den Brandt, P. A., CHANTARAKUL, N., KOETSAWANG, S., RACHAWAT, D., Palli, D., Black, A., Brinton, L. A., Freedman, D. M., Hartge, P., Hsing, A. W., Lacey, J. V., HOOVER, R. N., Schairer, C., Urban, M., Graff-Iversen, S., Selmer, R., Bain, C. J., Green, A. C., Purdie, D. M., Siskind, V., Webb, P. M., Moysich, K., McCann, S. E., Hannaford, P., Kay, C., Binns, C. W., Lee, A. H., Zhang, M., Ness, R. B., Nasca, P., Coogan, P. F., Palmer, J. R., Rosenberg, L., Kelsey, J., Paffenbarger, R., Whittemore, A., Katsouyanni, K., Trichopoulou, A., Trichopoulos, D., Tzonou, A., DABANCENS, A., Martinez, L., Molina, R., SALAS, O., Goodman, M. T., Lurie, G., Carney, M. E., Wilkens, L. R., Hartman, L., Manjer, J., Olsson, H., Grisso, J. A., Morgan, M., Wheeler, J. E., Bunker, C. H., Edwards, R. P., Modugno, F., Peeters, P. H., Casagrande, J., Pike, M. C., Ross, R. K., Wu, A. H., Miller, A. B., Kumle, M., Gram, I. T., Lund, E., McGowan, L., Shu, X. O., Zheng, W., Farley, T. M., Holck, S., MEIRIK, O., Risch, H. A. 2012; 13 (9): 946-956

  Abstract

  Smoking has been linked to mucinous ovarian cancer, but its effects on other ovarian cancer subtypes and on overall ovarian cancer risk are unclear, and the findings from most studies with relevant data are unpublished. To assess these associations, we review the published and unpublished evidence.Eligible epidemiological studies were identified by electronic searches, review articles, and discussions with colleagues. Individual participant data for 28,114 women with and 94,942 without ovarian cancer from 51 epidemiological studies were analysed centrally, yielding adjusted relative risks (RRs) of ovarian cancer in smokers compared with never smokers.After exclusion of studies with hospital controls, in which smoking could have affected recruitment, overall ovarian cancer incidence was only slightly increased in current smokers compared with women who had never smoked (RR 1·06, 95% CI 1·01-1·11, p=0·01). Of 17,641 epithelial cancers with specified histology, 2314 (13%) were mucinous, 2360 (13%) endometrioid, 969 (5%) clear-cell, and 9086 (52%) serous. Smoking-related risks varied substantially across these subtypes (p(heterogeneity)<0·0001). For mucinous cancers, incidence was increased in current versus never smokers (1·79, 95% CI 1·60-2·00, p<0·0001), but the increase was mainly in borderline malignant rather than in fully malignant tumours (2·25, 95% CI 1·91-2·65 vs 1·49, 1·28-1·73; p(heterogeneity)=0·01; almost half the mucinous tumours were only borderline malignant). Both endometrioid (0·81, 95% CI 0·72-0·92, p=0·001) and clear-cell ovarian cancer risks (0·80, 95% CI 0·65-0·97, p=0·03) were reduced in current smokers, and there was no significant association for serous ovarian cancers (0·99, 95% CI 0·93-1·06, p=0·8). These associations did not vary significantly by 13 sociodemographic and personal characteristics of women including their body-mass index, parity, and use of alcohol, oral contraceptives, and menopausal hormone therapy.The excess of mucinous ovarian cancers in smokers, which is mainly of tumours of borderline malignancy, is roughly counterbalanced by the deficit of endometrioid and clear-cell ovarian cancers. The substantial variation in smoking-related risks by tumour subtype is important for understanding ovarian carcinogenesis.Cancer Research UK and MRC.

  View details for DOI 10.1016/S1470-2045(12)70322-4

  View details for Web of Science ID 000308425600022

  View details for PubMedID 22863523

  View details for PubMedCentralID PMC3431503

• Prospective study of cytomegalovirus serostatus and prostate cancer risk in the Prostate Cancer Prevention Trial CANCER CAUSES & CONTROL Sutcliffe, S., Till, C., Gaydos, C. A., Jenkins, F. J., Goodman, P. J., Hoque, A. M., Hsing, A. W., Thompson, I. M., Zenilman, J. M., Nelson, W. G., De Marzo, A. M., Platz, E. A. 2012; 23 (9): 1511-1518

  Abstract

  To investigate serologic evidence of infection by cytomegalovirus (CMV), a herpesvirus with known oncogenic potential that has been detected in malignant prostate tissue, in relation to prostate cancer (PCa) risk in a large case-control study nested in the Prostate Cancer Prevention Trial (PCPT).Cases were men with a confirmed diagnosis of PCa after visit 2 (n = 614), and controls were men not diagnosed with PCa during the trial who also had a negative end-of-study biopsy (n = 616). Controls were frequency-matched to cases by age, treatment arm, and family history of PCa. Sera from visit 2 were tested for CMV IgG antibodies.No association was observed between CMV serostatus and PCa risk (adjusted CMV seroprevalence = 67.9 % for cases and 65.2 % for controls, odds ratio = 1.13, 95 % CI 0.89-1.45).Considering our null findings in the context of the full CMV literature, CMV infection, as measured by serostatus, does not appear to increase PCa risk.

  View details for DOI 10.1007/s10552-012-0028-5

  View details for Web of Science ID 000307401400011

  View details for PubMedID 22810146

  View details for PubMedCentralID PMC3433040

• Association between adult height, genetic susceptibility and risk of glioma INTERNATIONAL JOURNAL OF EPIDEMIOLOGY Kitahara, C. M., Wang, S. S., Melin, B. S., Wang, Z., Braganza, M., Inskip, P. D., Albanes, D., Andersson, U., Freeman, L. E., Buring, J. E., Carreon, T., Feychting, M., Gapstur, S. M., Gaziano, J. M., Giles, G. G., Hallmans, G., Hankinson, S. E., Henriksson, R., Hsing, A. W., Johansen, C., Linet, M. S., McKean-Cowdin, R., Michaud, D. S., Peters, U., Purdue, M. P., Rothman, N., Ruder, A. M., Sesso, H. D., Severi, G., Shu, X., Stevens, V. L., Visvanathan, K., Waters, M. A., White, E., Wolk, A., Zeleniuch-Jacquotte, A., Zheng, W., Hoover, R., Fraumeni, J. F., Chatterjee, N., Yeager, M., Chanock, S. J., Hartge, P., Rajaraman, P. 2012; 41 (4): 1075-1085

  View details for DOI 10.1093/ije/dys114

  View details for Web of Science ID 000308232200026

• Aspirin but not ibuprofen use is associated with reduced risk of prostate cancer: a PLCO Study BRITISH JOURNAL OF CANCER Shebl, F. M., Sakoda, L. C., Black, A., Koshiol, J., Andriole, G. L., Grubb, R., Church, T. R., Chia, D., Zhou, C., Chu, L. W., Huang, W., Peters, U., Kirsh, V. A., Chatterjee, N., Leitzmann, M. F., Hayes, R. B., Hsing, A. W. 2012; 107 (1): 207-214

  Abstract

  Although most epidemiological studies suggest that non-steroidal anti-inflammatory drug use is inversely associated with prostate cancer risk, the magnitude and specificity of this association remain unclear.We examined self-reported aspirin and ibuprofen use in relation to prostate cancer risk among 29 450 men ages 55-74 who were initially screened for prostate cancer from 1993 to 2001 in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Men were followed from their first screening exam until 31 December 2009, during which 3575 cases of prostate cancer were identified.After adjusting for potential confounders, the hazard ratios (HRs) of prostate cancer associated with <1 and ≥ 1 pill of aspirin daily were 0.98 (95% confidence interval (CI), 0.90-1.07) and 0.92 (95% CI: 0.85-0.99), respectively, compared with never use (P for trend 0.04). The effect of taking at least one aspirin daily was more pronounced when restricting the analyses to men older than age 65 or men who had a history of cardiovascular-related diseases or arthritis (HR (95% CI); 0.87 (0.78-0.97), 0.89 (0.80-0.99), and 0.88 (0.78-1.00), respectively). The data did not support an association between ibuprofen use and prostate cancer risk.Daily aspirin use, but not ibuprofen use, was associated with lower risk of prostate cancer risk.

  View details for DOI 10.1038/bjc.2012.227

  View details for Web of Science ID 000305888400032

  View details for PubMedID 22722313

• Detectable clonal mosaicism and its relationship to aging and cancer NATURE GENETICS Jacobs, K. B., Yeager, M., Zhou, W., Wacholder, S., Wang, Z., Rodriguez-Santiago, B., Hutchinson, A., Deng, X., Liu, C., Horner, M., Cullen, M., Epstein, C. G., Burdett, L., Dean, M. C., Chatterjee, N., Sampson, J., Chung, C. C., Kovaks, J., Gapstur, S. M., Stevens, V. L., Teras, L. T., Gaudet, M. M., Albanes, D., Weinstein, S. J., Virtamo, J., Taylor, P. R., Freedman, N. D., Abnet, C. C., Goldstein, A. M., Hu, N., Yu, K., Yuan, J., Liao, L., Ding, T., Qiao, Y., Gao, Y., Koh, W., Xiang, Y., Tang, Z., Fan, J., Aldrich, M. C., Amos, C., Blot, W. J., Bock, C. H., Gillanders, E. M., Harris, C. C., Haiman, C. A., Henderson, B. E., Kolonel, L. N., Le Marchand, L., McNeill, L. H., Rybicki, B. A., Schwartz, A. G., Signorello, L. B., Spitz, M. R., Wiencke, J. K., Wrensch, M., Wu, X., Zanetti, K. A., Ziegler, R. G., Figueroa, J. D., Garcia-Closas, M., Malats, N., Marenne, G., Prokunina-Olsson, L., Baris, D., Schwenn, M., Johnson, A., Landi, M. T., Goldin, L., Consonni, D., Bertazzi, P. A., Rotunno, M., Rajaraman, P., Andersson, U., Freeman, L. E., Berg, C. D., Buring, J. E., Butler, M. A., Carreon, T., Feychting, M., Ahlbom, A., Gaziano, J. M., Giles, G. G., Hallmans, G., Hankinson, S. E., Hartge, P., Henriksson, R., Inskip, P. D., Johansen, C., Landgren, A., McKean-Cowdin, R., Michaud, D. S., Melin, B. S., Peters, U., Ruder, A. M., Sesso, H. D., Severi, G., Shu, X., Visvanathan, K., White, E., Wolk, A., Zeleniuch-Jacquotte, A., Zheng, W., Silverman, D. T., Kogevinas, M., Gonzalez, J. R., Villa, O., Li, D., Duell, E. J., Risch, H. A., Olson, S. H., Kooperberg, C., Wolpin, B. M., Jiao, L., Hassan, M., Wheeler, W., Arslan, A. A., Bueno-de-Mesquita, H. B., Fuchs, C. S., Gallinger, S., Gross, M. D., Holly, E. A., Klein, A. P., LaCroix, A., Mandelson, M. T., Petersen, G., Boutron-Ruault, M., Bracci, P. M., Canzian, F., Chang, K., Cotterchio, M., Giovannucci, E. L., Goggins, M., Bolton, J. A., Jenab, M., Khaw, K., Krogh, V., Kurtz, R. C., Mcwilliams, R. R., Mendelsohn, J. B., Rabe, K. G., Riboli, E., Tjonneland, A., Tobias, G. S., Trichopoulos, D., Elena, J. W., Yu, H., Amundadottir, L., Stolzenberg-Solomon, R. Z., Kraft, P., Schumacher, F., Stram, D., Savage, S. A., Mirabello, L., Andrulis, I. L., Wunder, J. S., Patino Garcia, A., Sierrasesumaga, L., Barkauskas, D. A., Gorlick, R. G., Purdue, M., Chow, W., Moore, L. E., Schwartz, K. L., Davis, F. G., Hsing, A. W., Berndt, S. I., Black, A., Wentzensen, N., Brinton, L. A., Lissowska, J., Peplonska, B., McGlynn, K. A., Cook, M. B., Graubard, B. I., Kratz, C. P., Greene, M. H., Erickson, R. L., Hunter, D. J., Thomas, G., Hoover, R. N., Real, F. X., Fraumeni, J. F., Caporaso, N. E., Tucker, M., Rothman, N., Perez-Jurado, L. A., Chanock, S. J. 2012; 44 (6): 651-U68

  Abstract

  In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.

  View details for DOI 10.1038/ng.2270

  View details for Web of Science ID 000304551100011

  View details for PubMedID 22561519

• Interactions Between Genome-wide Significant Genetic Variants and Circulating Concentrations of Insulin-like Growth Factor 1, Sex Hormones, and Binding Proteins in Relation to Prostate Cancer Risk in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium AMERICAN JOURNAL OF EPIDEMIOLOGY Tsilidis, K. K., Travis, R. C., Appleby, P. N., Allen, N. E., Lindstrom, S., Schumacher, F. R., Cox, D., Hsing, A. W., Ma, J., Severi, G., Albanes, D., Virtamo, J., Boeing, H., Bueno-de-Mesquita, H. B., Johansson, M., Ramon Quiros, J., Riboli, E., Siddiq, A., Tjonneland, A., Trichopoulos, D., Tumino, R., Gaziano, J. M., Giovannucci, E., Hunter, D. J., Kraft, P., Stampfer, M. J., Giles, G. G., Andriole, G. L., Berndt, S. I., Chanock, S. J., Hayes, R. B., Key, T. J. 2012; 175 (9): 926-935

  Abstract

  Genome-wide association studies (GWAS) have identified many single nucleotide polymorphisms (SNPs) associated with prostate cancer risk. There is limited information on the mechanistic basis of these associations, particularly about whether they interact with circulating concentrations of growth factors and sex hormones, which may be important in prostate cancer etiology. Using conditional logistic regression, the authors compared per-allele odds ratios for prostate cancer for 39 GWAS-identified SNPs across thirds (tertile groups) of circulating concentrations of insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3), testosterone, androstenedione, androstanediol glucuronide, estradiol, and sex hormone-binding globulin (SHBG) for 3,043 cases and 3,478 controls in the Breast and Prostate Cancer Cohort Consortium. After allowing for multiple testing, none of the SNPs examined were significantly associated with growth factor or hormone concentrations, and the SNP-prostate cancer associations did not differ by these concentrations, although 4 interactions were marginally significant (MSMB-rs10993994 with androstenedione (uncorrected P = 0.008); CTBP2-rs4962416 with IGFBP-3 (uncorrected P = 0.003); 11q13.2-rs12418451 with IGF-1 (uncorrected P = 0.006); and 11q13.2-rs10896449 with SHBG (uncorrected P = 0.005)). The authors found no strong evidence that associations between GWAS-identified SNPs and prostate cancer are modified by circulating concentrations of IGF-1, sex hormones, or their major binding proteins.

  View details for DOI 10.1093/aje/kwr423

  View details for Web of Science ID 000303653000010

  View details for PubMedID 22459122

• Ovarian Cancer and Body Size: Individual Participant Meta-Analysis Including 25,157 Women with Ovarian Cancer from 47 Epidemiological Studies PLOS MEDICINE Beral, V., Hermon, C., Peto, R., Reeves, G., Brinton, L., Marchbanks, P., Negri, E., Ness, R., Peeters, P. H., Vessey, M., Calle, E. E., Gapstur, S. M., Patel, A. V., Dal Maso, L., Talamini, R., Chetrit, A., Hirsh-Yechezkel, G., Lubin, F., Sadetzki, S., Allen, N., Bull, D., Callaghan, K., Crossley, B., Gaitskell, K., Goodill, A., Green, J., Key, T., Moser, K., Collins, R., DOLL, R., Gonzalez, C. A., Lee, N., Ory, H. W., Peterson, H. B., Wingo, P. A., Martin, N., PARDTHAISONG, T., SILPISORNKOSOL, S., Theetranont, C., BOOSIRI, B., CHUTIVONGSE, S., Jimakorn, P., Virutamasen, P., Wongsrichanalai, C., Tjonneland, A., Titus-Ernstoff, L., Byers, T., Rohan, T., Mosgaard, B. J., Yeates, D., Freudenheim, J. L., Chang-Claude, J., Kaaks, R., Anderson, K. E., Folsom, A., Robien, K., Rossing, M. A., Thomas, D. B., Weiss, N. S., Riboli, E., Clavel-Chapelon, F., Cramer, D., Hankinson, S. E., Tworoger, S. S., Franceschi, S., La Vecchia, C., Magnusson, C., Riman, T., Weiderpass, E., Wolk, A., Schouten, L. J., van den Brandt, P. A., CHANTARAKUL, N., KOETSAWANG, S., RACHAWAT, D., Palli, D., Black, A., de Gonzalez, A. B., Freedman, D. M., Hartge, P., Hsing, A. W., Lacey, J. V., HOOVER, R. N., Schairer, C., Graff-Iversen, S., Selmer, R., Bain, C. J., Green, A. C., Purdie, D. M., Siskind, V., Webb, P. M., McCann, S. E., Hannaford, P., Kay, C., Binns, C. W., Lee, A. H., Zhang, M., Ness, R. B., Nasca, P., Coogan, P. F., Palmer, J. R., Rosenberg, L., Kelsey, J., Paffenbarger, R., Whittemore, A., Katsouyanni, K., Trichopoulou, A., Trichopoulos, D., Tzonou, A., DABANCENS, A., Martinez, L., Molina, R., SALAS, O., Goodman, M. T., Lurie, G., Carney, M. E., Wilkens, L. R., Hartman, L., Manjer, J., Olsson, H., Grisso, J. A., Morgan, M., Wheeler, J. E., Casagrande, J., Pike, M. C., Ross, R. K., Wu, A. H., Miller, A. B., Kumle, M., Lund, E., McGowan, L., Shu, X. O., Zheng, W., Farley, T. M., Holck, S., MEIRIK, O., Risch, H. A. 2012; 9 (4)

  Abstract

  Only about half the studies that have collected information on the relevance of women's height and body mass index to their risk of developing ovarian cancer have published their results, and findings are inconsistent. Here, we bring together the worldwide evidence, published and unpublished, and describe these relationships.Individual data on 25,157 women with ovarian cancer and 81,311 women without ovarian cancer from 47 epidemiological studies were collected, checked, and analysed centrally. Adjusted relative risks of ovarian cancer were calculated, by height and by body mass index. Ovarian cancer risk increased significantly with height and with body mass index, except in studies using hospital controls. For other study designs, the relative risk of ovarian cancer per 5 cm increase in height was 1.07 (95% confidence interval [CI], 1.05-1.09; p<0.001); this relationship did not vary significantly by women's age, year of birth, education, age at menarche, parity, menopausal status, smoking, alcohol consumption, having had a hysterectomy, having first degree relatives with ovarian or breast cancer, use of oral contraceptives, or use of menopausal hormone therapy. For body mass index, there was significant heterogeneity (p<0.001) in the findings between ever-users and never-users of menopausal hormone therapy, but not by the 11 other factors listed above. The relative risk for ovarian cancer per 5 kg/m(2) increase in body mass index was 1.10 (95% CI, 1.07-1.13; p<0.001) in never-users and 0.95 (95% CI, 0.92-0.99; p=0.02) in ever-users of hormone therapy.Ovarian cancer is associated with height and, among never-users of hormone therapy, with body mass index. In high-income countries, both height and body mass index have been increasing in birth cohorts now developing the disease. If all other relevant factors had remained constant, then these increases in height and weight would be associated with a 3% increase in ovarian cancer incidence per decade. Please see later in the article for the Editors' Summary.

  View details for DOI 10.1371/journal.pmed.1001200

  View details for Web of Science ID 000303393800003

  View details for PubMedID 22606070

  View details for PubMedCentralID PMC3317899

• A genome-wide association study identifies a novel susceptibility locus for renal cell carcinoma on 12p11.23 HUMAN MOLECULAR GENETICS Wu, X., Scelo, G., Purdue, M. P., Rothman, N., Johansson, M., Ye, Y., Wang, Z., Zelenika, D., Moore, L. E., Wood, C. G., Prokhortchouk, E., Gaborieau, V., Jacobs, K. B., Chow, W., Toro, J. R., Zaridze, D., Lin, J., Lubinski, J., Trubicka, J., Szeszenia-Dabrowska, N., Lissowska, J., Rudnai, P., Fabianova, E., Mates, D., Jinga, V., Bencko, V., Slamova, A., Holcatova, I., Navratilova, M., Janout, V., Boffetta, P., Colt, J. S., Davis, F. G., Schwartz, K. L., Banks, R. E., Selby, P. J., Harnden, P., Berg, C. D., Hsing, A. W., Grubb, R. L., Boeing, H., Vineis, P., Clavel-Chapelon, F., Palli, D., Tumino, R., Krogh, V., Panico, S., Duell, E. J., Ramon Quiros, J., Sanchez, M., Navarro, C., Ardanaz, E., Dorronsoro, M., Khaw, K., Allen, N. E., Bueno-de-Mesquita, H. B., Peeters, P. H., Trichopoulos, D., Linseisen, J., Ljungberg, B., Overvad, K., Tjonneland, A., Romieu, I., Riboli, E., Stevens, V. L., Thun, M. J., Diver, W. R., Gapstur, S. M., Pharoah, P. D., Easton, D. F., Albanes, D., Virtamo, J., Vatten, L., Hveem, K., Fletcher, T., Koppova, K., Cussenot, O., Cancel-Tassin, G., Benhamou, S., Hildebrandt, M. A., Pu, X., Foglio, M., Lechner, D., Hutchinson, A., Yeager, M., Fraumeni, J. F., Lathrop, M., Skryabin, K. G., McKay, J. D., Gu, J., Brennan, P., Chanock, S. J. 2012; 21 (2): 456-462

  Abstract

  Renal cell carcinoma (RCC) is the most lethal urologic cancer. Only two common susceptibility loci for RCC have been confirmed to date. To identify additional RCC common susceptibility loci, we conducted an independent genome-wide association study (GWAS). We analyzed 533 191 single nucleotide polymorphisms (SNPs) for association with RCC in 894 cases and 1516 controls of European descent recruited from MD Anderson Cancer Center in the primary scan, and validated the top 500 SNPs in silico in 3772 cases and 8505 controls of European descent involved in the only published GWAS of RCC. We identified two common variants in linkage disequilibrium, rs718314 and rs1049380 (r(2) = 0.64, D ' = 0.84), in the inositol 1,4,5-triphosphate receptor, type 2 (ITPR2) gene on 12p11.23 as novel susceptibility loci for RCC (P = 8.89 × 10(-10) and P = 6.07 × 10(-9), respectively, in meta-analysis) with an allelic odds ratio of 1.19 [95% confidence interval (CI): 1.13-1.26] for rs718314 and 1.18 (95% CI: 1.12-1.25) for rs1049380. It has been recently identified that rs718314 in ITPR2 is associated with waist-hip ratio (WHR) phenotype. To our knowledge, this is the first genetic locus associated with both cancer risk and WHR.

  View details for DOI 10.1093/hmg/ddr479

  View details for Web of Science ID 000298658300019

  View details for PubMedID 22010048

• Genome-wide association study of prostate cancer in men of African ancestry identifies a susceptibility locus at 17q21 NATURE GENETICS Haiman, C. A., Chen, G. K., Blot, W. J., Strom, S. S., Berndt, S. I., Kittles, R. A., Rybicki, B. A., Isaacs, W. B., Ingles, S. A., Stanford, J. L., Diver, W. R., Witte, J. S., Hsing, A. W., Nemesure, B., Rebbeck, T. R., Cooney, K. A., Xu, J., Kibel, A. S., Hu, J. J., John, E. M., Gueye, S. M., Watya, S., Signorello, L. B., Hayes, R. B., Wang, Z., Yeboah, E., Tettey, Y., Cai, Q., Kolb, S., Ostrander, E. A., Zeigler-Johnson, C., Yamamura, Y., Neslund-Dudas, C., Haslag-Minoff, J., Wu, W., Thomas, V., Allen, G. O., Murphy, A., Chang, B., Zheng, S. L., Leske, M. C., Wu, S., Ray, A. M., Hennis, A. J., Thun, M. J., Carpten, J., Casey, G., Carter, E. N., Duarte, E. R., Xia, L. Y., Sheng, X., Wan, P., Pooler, L. C., Cheng, I., Monroe, K. R., Schumacher, F., Le Marchand, L., Kolonel, L. N., Chanock, S. J., Van Den Berg, D., Stram, D. O., Henderson, B. E. 2011; 43 (6): 570-U103

  Abstract

  In search of common risk alleles for prostate cancer that could contribute to high rates of the disease in men of African ancestry, we conducted a genome-wide association study, with 1,047,986 SNP markers examined in 3,425 African-Americans with prostate cancer (cases) and 3,290 African-American male controls. We followed up the most significant 17 new associations from stage 1 in 1,844 cases and 3,269 controls of African ancestry. We identified a new risk variant on chromosome 17q21 (rs7210100, odds ratio per allele = 1.51, P = 3.4 × 10(-13)). The frequency of the risk allele is ∼5% in men of African descent, whereas it is rare in other populations (<1%). Further studies are needed to investigate the biological contribution of this allele to prostate cancer risk. These findings emphasize the importance of conducting genome-wide association studies in diverse populations.

  View details for DOI 10.1038/ng.839

  View details for Web of Science ID 000291017000015

  View details for PubMedID 21602798

  View details for PubMedCentralID PMC3102788

• Validation of Genome-Wide Prostate Cancer Associations in Men of African Descent CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Chang, B., Spangler, E., Gallagher, S., Haiman, C. A., Henderson, B., Isaacs, W., Benford, M. L., Kidd, L. R., Cooney, K., Strom, S., Ingles, S. A., Stern, M. C., Corral, R., Joshi, A. D., Xu, J., Giri, V. N., Rybicki, B., Neslund-Dudas, C., Kibel, A. S., Thompson, I. M., Leach, R. J., Ostrander, E. A., Stanford, J. L., Witte, J., Casey, G., Eeles, R., Hsing, A. W., Chanock, S., Hu, J. J., John, E. M., Park, J., Stefflova, K., Zeigler-Johnson, C., Rebbeck, T. R. 2011; 20 (1): 23-32

  Abstract

  Genome-wide association studies (GWAS) have identified numerous prostate cancer susceptibility alleles, but these loci have been identified primarily in men of European descent. There is limited information about the role of these loci in men of African descent.We identified 7,788 prostate cancer cases and controls with genotype data for 47 GWAS-identified loci.We identified significant associations for SNP rs10486567 at JAZF1, rs10993994 at MSMB, rs12418451 and rs7931342 at 11q13, and rs5945572 and rs5945619 at NUDT10/11. These associations were in the same direction and of similar magnitude as those reported in men of European descent. Significance was attained at all reported prostate cancer susceptibility regions at chromosome 8q24, including associations reaching genome-wide significance in region 2.We have validated in men of African descent the associations at some, but not all, prostate cancer susceptibility loci originally identified in European descent populations. This may be due to the heterogeneity in genetic etiology or in the pattern of genetic variation across populations.The genetic etiology of prostate cancer in men of African descent differs from that of men of European descent.

  View details for DOI 10.1158/1055-9965.EPI-10-0698

  View details for Web of Science ID 000285972800003

  View details for PubMedID 21071540

  View details for PubMedCentralID PMC3110616

• Soy and isoflavone consumption in relation to prostate cancer risk in China CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Lee, M. M., Gomez, S. L., Chang, J. S., Wey, M., Wang, R. T., Hsing, A. W. 2003; 12 (7): 665-668

  Abstract

  This case-control study in China evaluated the effect of soy food consumption and isoflavones (genistein and daidzein) on the risk of prostate cancer. One hundred and thirty-three cases and 265 age- and residential community-matched controls between the ages of 50 and 89 years were interviewed in person between 1989 and 1992. Usual consumption of soy foods and isoflavones was assessed using a food frequency questionnaire developed in China and a nutrient database developed and validated in Asian-American populations. The age- and total calorie-adjusted odds ratio (OR) of prostate cancer risk comparing the highest tertile of tofu intake to the lowest tertile was 0.58 [95% confidence interval (CI), 0.35-0.96]. There were also statistically significant associations comparing the highest quartile of intake of soy foods (OR, 0.51; 95% CI, 0.28-0.95) and genistein (OR, 0.53; 95% CI, 0.29-0.97) with the lowest quartiles. There was also an indication of a reduced risk associated with intake of daidzein (OR, 0.56; 95% CI, 0.31-1.04 for the highest versus lowest quartile). Our results indicate a reduced risk of prostate cancer associated with consumption of soy foods and isoflavones. These findings should be confirmed in longitudinal follow-up studies in populations with varying risk of prostate cancer.

  View details for Web of Science ID 000184311700014

  View details for PubMedID 12869409