Academic Appointments

Administrative Appointments

  • Member, Stanford Cancer Institute (2006 - Present)
  • Research Scientist II, CPIC (2006 - Present)
  • Consulting Assistant Professor, Department of Health Research and Policy, Stanford University School of Medicine (2007 - Present)
  • Associate Member, Canary Center at Stanford for Cancer Early Detection (2015 - Present)

Professional Education

  • B.S., University of Michigan, Biology (1987)
  • M.P.H., Tulane University, Epidemiology (1992)
  • Ph.D., Stanford University School of Medicine, Epidemiology (2002)

Research & Scholarship

Current Research and Scholarly Interests

Genetic epidemiology: Identifying genes that increase susceptibility to cancer or are related to poor survival is a primary interest of Dr. Oakley-Girvan. She is part of the International Consortium for Prostate Cancer Genetics, a member in an international breast and ovarian cancer research group and part of a thyroid cancer alliance. Through these collaborative teams, which include a broad base of investigators from many institutions and genetic samples from many projects, Dr. Oakley-Girvan is able to focus on investigating genes that may increase a person's susceptibility to prostate, ovarian, thyroid and breast cancer. In addition, she aims to identify environmental factors that reduce an individual's risk of these cancers, as well as decrease their risk of cancer recurrence and improve their chance of survival.

Survivorship: Dr. Oakley-Girvan is also actively evaluating factors (patient reported, clinically reported and biomarkers such as telomeres) associated with cancer treatment choice, quality of care, treatment outcomes, quality of life and survivorship. With interests throughout the cancer survivorship continuum and an emphasis on understanding why there are disparities in survivor care, Dr. Oakley-Girvan is also focused on creating solutions, particularly ones that resonate with communities. She plans to follow her current studies with education and behavioral intervention projects that will effect meaningful change, improve the life of survivors and help eliminate, or, at the very least, reduce cancer health care disparities.

Mobile Health: Dr. Oakley-Girvan has recently completed a project with a community based clinical provider that evaluated the use of text messages to impact time to clinical resolution of abnormal mammograms. Results were positive and the next steps to expand to include easily scalable mobile health applications and digital therapeutics on a HIPAA compliant platform are underway.

Big Data on an Individual Level: In several collaborations with colleagues, Dr. Oakley-Girvan is facilitating the capture of multiple data streams that include biosensor data, biomarkers such as telomeres, cytokines and epigenetics, self-reported data, and comprehensive clinical data through electronic health records.


Graduate and Fellowship Programs


All Publications

  • Achieving value in mobile health applications for cancer survivors. Journal of cancer survivorship Davis, S. W., Oakley-Girvan, I. 2017


    This study aimed to identify appropriate development and testing strategies for mobile health applications for cancer survivors.In January of 2016, we conducted a PubMed search for mobile applications for cancer survivors. A total of 32 articles were selected for inclusion, including 13 review articles, and 19 articles describing an mHealth application or intervention. We assessed mobile app development and testing strategies and standards as described in these articles.We identified seven elements of patient empowerment applications for cancer survivors, strategies for application development that take advantage of smartphone capabilities, issues for consideration in developing new applications, and steps for creating user-centered mobile health applications that provide meaningful value for cancer survivors. However, few mobile health apps implemented empowerment elements, underwent rigorous design approaches, or included assessment of use in the cancer survivor population.There is tremendous potential for mobile health apps to benefit cancer survivors. However, there are specific issues for consideration in developing new applications and steps for creating user-centered applications which are not routinely used. This diminishes the value for the cancer survivor population but could be easily addressed through standardized development and testing procedures.Smartphone applications have the potential to improve the cancer survivorship experience, but users should look for evidence that the application was appropriately developed and tested.

    View details for DOI 10.1007/s11764-017-0608-1

    View details for PubMedID 28342093

  • Geographic variation in Medicare treatment costs and outcomes for advanced head and neck cancer ORAL ONCOLOGY Divi, V., Tao, L., Whittemore, A., Oakley-Girvan, I. 2016; 61: 83-88


    Advanced head and neck cancer (HNC) is a complex group of diseases that requires the input and coordination of multiple providers. While there are general guidelines for treatment, there is also considerable variation in how patients are treated, and how long they survive after treatment. It is unclear how the treatment variations relate to treatment costs and survival.We identified 3678 Medicare patients with advanced HNC treated in 12 US regions between 2004 and 2009 using the linked database containing Medicare and Surveillance Epidemiology and End Results (SEER) data. We calculated average cost per patient during the period three months before to 12months after diagnosis for each region. Costs included inpatient hospital, outpatient, physician, and durable medical equipment charges. We also calculated three-year overall survival for each of the regions.The mean cost-per-patient varied substantially among the regions, ranging from $51,857 for Utah to $82,181 for Detroit. Utah incurred the lowest total costs within one year of advanced HNC diagnosis ($51,857 per patient, 95% CI $42,285-$61,429), whereas Detroit had the highest costs ($82,181 per patient, 95% CI $74,752-$89,610). Overall survival also varied among the regions, ranging from 45months in Kentucky to 58months in Washington. There was little correlation between expenditures and length of survival, with correlation coefficient of 0.0088.Despite significant variation in both expenditures and survival among the regions, we found no correlation between costs and mean survival time, suggesting that more costly care did not lead to improved outcomes.

    View details for DOI 10.1016/j.oraloncology.2016.08.018

    View details for Web of Science ID 000384695400013

    View details for PubMedID 27688109

  • Number of positive nodes is superior to the lymph node ratio and American Joint Committee on Cancer N staging for the prognosis of surgically treated head and neck squamous cell carcinomas CANCER Roberts, T. J., Colevas, A. D., Hara, W., Holsinger, F. C., Oakley-Girvan, I., Divi, V. 2016; 122 (9): 1388-1397


    Recent changes in head and neck cancer epidemiology have created a need for improved lymph node prognostics. This article compares the prognostic value of the number of positive nodes (pN) with the value of the lymph node ratio (LNR) and American Joint Committee on Cancer (AJCC) N staging in surgical patients.The Surveillance, Epidemiology, and End Results database was used to identify cases of head and neck squamous cell carcinomas from 2004 to 2012. The sample was grouped by the AJCC N stage, LNR, and pN and was analyzed with Kaplan-Meier and multivariate Cox proportional hazards models. The sample was also analyzed by the site of the primary tumor.This study identified 12,437 patients. Kaplan-Meier survival curves showed superior prognostic ability for LNR and pN staging in comparison with AJCC staging. Patients with a pN value > 5 had the worst overall survival (5-year survival rate, 16%). Patients with oropharyngeal tumors had better outcomes for all groupings, and a pN value > 5 for oropharyngeal cancers was associated with decreased survival. Multivariate regressions demonstrated larger hazard ratios (HRs) and a lower Akaike information criterion for the pN model versus the AJCC stage and LNR models. The HRs were 1.78 (95% confidence interval, 1.62-1.95) for a pN value of 1, 2.53 (95% confidence interval, 2.32-2.75) for a pN value of 2 to 5, and 4.64 (95% confidence interval, 4.18-5.14) for a pN value > 5.The pN models demonstrated superior prognostic value in comparison with the LNR and AJCC N staging. Future modifications of the nodal staging system should be based on the pN with a separate system for oropharyngeal cancers. Future trials should consider examining adjuvant treatment escalation in patients with >5 lymph nodes. Cancer 2016;122:1388-1397. © 2016 American Cancer Society.

    View details for DOI 10.1002/cncr.29932

    View details for Web of Science ID 000374706500010

    View details for PubMedID 26969807

  • Text Messaging May Improve Abnormal Mammogram Follow-Up in Latinas ONCOLOGY NURSING FORUM Oakley-Girvan, I., Londono, C., Canchola, A., Davis, S. W. 2016; 43 (1): 36-43


    To develop and pilot test a text message notification process to reduce follow-up time for women with abnormal mammograms..Formative analysis; randomized trial with delayed intervention control group..Tiburcio Vasquez Health Clinic (TVHC), a federally qualified health center in Hayward, California..29 Spanish-speaking Latinas with abnormal mammograms..A Spanish text message was developed based on findings from two focus groups and five interviews with TVHC healthcare providers. Thirteen women were assigned to receive text messages within 24 hours of receipt of abnormal mammogram by TVHC (intervention group) and 16 to receive text messages four weeks later (delayed intervention group)..Number of days between the abnormal mammogram and the return for follow-up appointment..The median number of days from the abnormal mammogram report to the return for follow-up was 23 days for the intervention group and 59 days for the delayed intervention group (p = 0.0569)..This study successfully developed a text message that, in Latinas, may decrease the time from receipt of an abnormal mammogram report to attendance at a follow-up visit..This simple, low-cost approach could result in earlier detection of breast cancers, lowering morbidity and mortality among Latinas.

    View details for DOI 10.1188/16.ONF.36-43

    View details for Web of Science ID 000373612900010

    View details for PubMedID 26679443

  • Indicators of microbial-rich environments and the development of papillary thyroid cancer in the California Teachers Study CANCER EPIDEMIOLOGY Clarke, C. A., Reynolds, P., Oakley-Girvan, I., Lee, E., Lu, Y., Yang, J., Moy, L. M., Bernstein, L., Horn-Ross, P. L. 2015; 39 (4): 548-553


    Little epidemiologic research has focused on the role of immune function in papillary thyroid cancer risk despite scattered observations suggesting it may be important (e.g., hygiene hypothesis). Here we investigate papillary thyroid cancer risk associated with self-reported living environments across the lifespan reflecting immunologically relevant exposures to microbial-rich environments.Among 61,803 eligible participants in the California Teachers Study cohort, 100 were diagnosed with invasive papillary thyroid cancer between 2005 and 2012. Multivariate Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI).Living in a rural area during early childhood was associated with significantly reduced risk of developing papillary thyroid cancer as an adult (HR=0.51, 95% CI: 0.28-0.94). Specifically, reduced risks were observed for living within a half mile of hoofed animals (HR=0.47, 95% CI: 0.26-0.84), as was having an indoor dog or cat (HR=0.51, 95% CI: 0.32-0.80). Neither sharing a bedroom or living in a rented home as a child nor attending daycare or kindergarten was associated with reduced risk.Early childhood exposures to hoofed animals or indoor furry pets were associated with reduced risk of subsequently developing papillary thyroid cancer.Our findings point to immunologically relevant, early-life exposures to microbial-rich environments as potentially important in reducing thyroid cancer risk, consistent with the hygiene hypothesis and suggesting that certain, possibly animal-derived, microbial exposures may be important to immune calibration or priming.

    View details for DOI 10.1016/j.canep.2015.04.014

    View details for Web of Science ID 000360043300010

    View details for PubMedCentralID PMC4532633

  • mHealth Education Applications Along the Cancer Continuum JOURNAL OF CANCER EDUCATION Davis, S. W., Oakley-Girvan, I. 2015; 30 (2): 388-394


    The majority of adults worldwide own a mobile phone, including those in under-resourced communities. Mobile health (mhealth) education technologies present a promising mechanism for improving cancer prevention, treatment, and follow-up. The purpose of this study was to summarize the literature related to mobile phone (mhealth) applications for patient education specific to cancer and identify current recommendations from randomized studies. In particular, we were interested in identifying mobile phone applications along the cancer continuum, from cancer prevention to survivorship. The authors identified 28 articles reporting on mobile applications for patients related to cancer. Articles were identified in all categories along the cancer continuum, including health professional involvement in application development. Of these, six involved direct patient education, and eight focused on improving patient/professional communication and patient self-management. However, only six of the studies were randomized interventions. The potential for mobile applications to help overcome the "health care gap" has not yet been realized in the studies from the USA that were reviewed for this paper. However, early recommendations are emerging that support the use of mHealth communications to change behaviors for cancer prevention, early detection, and symptom management and improved patient-provider communication. Recommendations include short messages, use of multiple modalities as patient characteristics dictate comfort with mHealth communication, and the inclusion of patients and health professionals to develop and test applications. Tailoring mHealth to particular cultures, languages, and ethnic groups may also represent a unique possibility to provide accessible information and education at minimal cost for under-resourced communities and individuals.

    View details for DOI 10.1007/s13187-014-0761-4

    View details for Web of Science ID 000353808100027

    View details for PubMedID 25482319

  • Continued rapid increase in thyroid cancer incidence in california: trends by patient, tumor, and neighborhood characteristics. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology Horn-Ross, P. L., Lichtensztajn, D. Y., Clarke, C. A., Dosiou, C., Oakley-Girvan, I., Reynolds, P., Gomez, S. L., Nelson, D. O. 2014; 23 (6): 1067-1079


    Thyroid cancer incidence is increasing worldwide. Incorporating 22 years of incidence data through 2009, we extend examination of these trends among a wide array of subgroups defined by patient (age, sex, race/ethnicity, and nativity), tumor (tumor size and stage), and neighborhood (socioeconomic status and residence in ethnic enclaves) characteristics, to identify possible reasons for this increase.Thyroid cancer incidence data on 10,940 men and 35,147 women were obtained from the California Cancer Registry for 1988-2009. Population data were obtained from the 1990 and 2000 U.S. Census. Incidence rates and 95% confidence intervals (CI) were calculated and incidence trends were evaluated using Joinpoint regression to evaluate the timing and magnitude of change [annual percentage change (APC) and rate ratios].The incidence of papillary thyroid cancer continues to increase in both men (APC, 5.4; 95% CI, 4.5-6.3 for 1998-2009) and women (APC, 3.8; 95% CI, 3.4-4.2 for 1998-2001 and APC, 6.3; 95% CI, 5.7-6.9 for 2001-2009). Increasing incidence was observed in all subgroups examined.Although some variation in the magnitude or temporality of the increase in thyroid cancer incidence exists across subgroups, the patterns (i) suggest that changes in diagnostic technology alone do not account for the observed trends and (ii) point to the importance of modifiable behavioral, lifestyle, or environmental factors in understanding this epidemic.Given the dramatic and continued increase in thyroid cancer incidence rates, studies addressing the causes of these trends are critical. Cancer Epidemiol Biomarkers Prev; 23(6); 1067-79. ©2014 AACR.

    View details for DOI 10.1158/1055-9965.EPI-13-1089

    View details for PubMedID 24842625

  • Association analysis of 9,560 prostate cancer cases from the International Consortium of Prostate Cancer Genetics confirms the role of reported prostate cancer associated SNPs for familial disease HUMAN GENETICS Teerlink, C. C., Thibodeau, S. N., McDonnell, S. K., Schaid, D. J., Rinckleb, A., Maier, C., Vogel, W., Cancel-Tassin, G., Egrot, C., Cussenot, O., Foulkes, W. D., Giles, G. G., Hopper, J. L., Severi, G., Eeles, R., Easton, D., Kote-Jarai, Z., Guy, M., Cooney, K. A., Ray, A. M., Zuhlke, K. A., Lange, E. M., FitzGerald, L. M., Stanford, J. L., Ostrander, E. A., Wiley, K. E., Isaacs, S. D., Walsh, P. C., Isaacs, W. B., Wahlfors, T., Tammela, T., Schleutker, J., Wiklund, F., Gronberg, H., Emanuelsson, M., Carpten, J., Bailey-Wilson, J., Whittemore, A. S., Oakley-Girvan, I., Hsieh, C., Catalona, W. J., Zheng, S. L., Jin, G., Lu, L., Xu, J., Camp, N. J., Cannon-Albright, L. A. 2014; 133 (3): 347-356


    Previous GWAS studies have reported significant associations between various common SNPs and prostate cancer risk using cases unselected for family history. How these variants influence risk in familial prostate cancer is not well studied. Here, we analyzed 25 previously reported SNPs across 14 loci from prior prostate cancer GWAS. The International Consortium for Prostate Cancer Genetics (ICPCG) previously validated some of these using a family-based association method (FBAT). However, this approach suffered reduced power due to the conditional statistics implemented in FBAT. Here, we use a case-control design with an empirical analysis strategy to analyze the ICPCG resource for association between these 25 SNPs and familial prostate cancer risk. Fourteen sites contributed 12,506 samples (9,560 prostate cancer cases, 3,368 with aggressive disease, and 2,946 controls from 2,283 pedigrees). We performed association analysis with Genie software which accounts for relationships. We analyzed all familial prostate cancer cases and the subset of aggressive cases. For the familial prostate cancer phenotype, 20 of the 25 SNPs were at least nominally associated with prostate cancer and 16 remained significant after multiple testing correction (p ≤ 1E (-3)) occurring on chromosomal bands 6q25, 7p15, 8q24, 10q11, 11q13, 17q12, 17q24, and Xp11. For aggressive disease, 16 of the SNPs had at least nominal evidence and 8 were statistically significant including 2p15. The results indicate that the majority of common, low-risk alleles identified in GWAS studies for all prostate cancer also contribute risk for familial prostate cancer, and that some may contribute risk to aggressive disease.

    View details for DOI 10.1007/s00439-013-1384-2

    View details for Web of Science ID 000331622700009

    View details for PubMedID 24162621

  • Cardiovascular risk factors among long-term survivors of breast, prostate, colorectal, and gynecologic cancers: a gap in survivorship care? JOURNAL OF CANCER SURVIVORSHIP-RESEARCH AND PRACTICE Weaver, K. E., Foraker, R. E., Alfano, C. M., Rowland, J. H., Arora, N. K., Bellizzi, K. M., Hamilton, A. S., Oakley-Girvan, I., Keel, G., Aziz, N. M. 2013; 7 (2): 253-261


    Individuals diagnosed with high survival cancers will often die of cardiovascular disease (CVD) rather than a recurrence of their cancer, yet CVD risk factors may be overlooked during survivorship care. We assess the prevalence of CVD risk factors among long-term cancer survivors and compare results to survey data from the general population in the same geographic region. We also characterize how often at-risk survivors discuss CVD-related health behaviors with their health care providers.Survivors (n = 1,582) of breast, prostate, colorectal, and gynecologic cancers, 4-14 years after diagnosis, were recruited from two California cancer registries for a cross-sectional mail survey. We assessed CVD risk factors, including smoking, body mass index, physical inactivity, hypercholesterolemia, hypertension, and diabetes, as well as report of discussions with health care providers about diet, exercise, smoking, and lifestyle change assistance.With the exception of current smoking, CVD risk factors were more common among survivors than the general adult population. Of survivors, 62.0 % were overweight or obese, 55.0 % reported hypertension, 20.7 % reported diabetes, 18.1 % were inactive, and 5.1 % were current smokers. Compared to white, non-Hispanic survivors, Hispanic (b = 0.37, p = 0.007) and African-American (b = 0.66, p < 0.0001), but not Asian, survivors reported significantly more risk factors. One in three survivors with one or more risk factors for CVD did not report a health promotion discussion with their health care providers.CVD risk factors are common among long-term survivors, but many at-risk survivors may not discuss lifestyle prevention with their health care team. Primary care and oncology should work together to deliver optimal survivorship care that addresses CVD risk factors, as well as prevalent disease.Cardiovascular disease may compromise cancer survivors' long-term health and well-being, yet cardiovascular risk factors may be overlooked during survivorship care. We document that CVD risk factors are common among cancers survivors, yet nearly a third of survivors do not report health promotion discussions with their medical teams. Survivors should be aware of their cardiovascular risk factors and initiate discussions with their medical teams about health promotion topics, if appropriate.

    View details for DOI 10.1007/s11764-013-0267-9

    View details for Web of Science ID 000317862900010

    View details for PubMedID 23417882

  • Health information needs and health-related quality of life in a diverse population of long-term cancer survivors PATIENT EDUCATION AND COUNSELING Kent, E. E., Arora, N. K., Rowland, J. H., Bellizzi, K. M., Forsythe, L. P., Hamilton, A. S., Oakley-Girvan, I., Beckjord, E. B., Aziz, N. M. 2012; 89 (2): 345-352


    To investigate health information needs and their association with health-related quality of life (HRQOL) in a diverse, population-based sample of long-term cancer survivors.We analyzed health information needs from 1197 cancer survivors 4-14 years post-diagnosis drawn from two cancer registries in California. Multivariable regression models were used to identify factors associated with endorsement of total number and different categories of needs. The relationship between number of needs and HRQOL and effect modification by confidence for obtaining information was examined.Survivors reported a high prevalence of unmet information needs in the following categories: side effects & symptoms: 75.8%; tests & treatment: 71.5%; health promotion: 64.5%; interpersonal & emotional: 60.2%; insurance: 39.0%; and sexual functioning & fertility: 34.6%. Survivors who were younger, non-White, and did not receive but wanted a written treatment summary reported a higher number of needs. Number of information needs was inversely related to mental well-being, particularly for those with low confidence for obtaining information (P<0.05).These patterns suggest disparities in access to important health information in long-term survivors and that affect HRQOL.Findings suggest a need for tailored interventions to equip survivors with comprehensive health information and to bolster skills for obtaining information.

    View details for DOI 10.1016/j.pec.2012.08.014

    View details for Web of Science ID 000311766700019

    View details for PubMedID 23021856

  • Validation of prostate cancer risk-related loci identified from genome-wide association studies using family-based association analysis: evidence from the International Consortium for Prostate Cancer Genetics (ICPCG) HUMAN GENETICS Jin, G., Lu, L., Cooney, K. A., Ray, A. M., Zuhlke, K. A., Lange, E. M., Cannon-Albright, L. A., Camp, N. J., Teerlink, C. C., FitzGerald, L. M., Stanford, J. L., Wiley, K. E., Isaacs, S. D., Walsh, P. C., Foulkes, W. D., Giles, G. G., Hopper, J. L., Severi, G., Eeles, R., Easton, D., Kote-Jarai, Z., Guy, M., Rinckleb, A., Maier, C., Vogel, W., Cancel-Tassin, G., Egrot, C., Cussenot, O., Thibodeau, S. N., McDonnell, S. K., Schaid, D. J., Wiklund, F., Gronberg, H., Emanuelsson, M., Whittemore, A. S., Oakley-Girvan, I., Hsieh, C., Wahlfors, T., Tammela, T., Schleutker, J., Catalona, W. J., Zheng, S. L., Ostrander, E. A., Isaacs, W. B., Xu, J. 2012; 131 (7): 1095-1103


    Multiple prostate cancer (PCa) risk-related loci have been discovered by genome-wide association studies (GWAS) based on case-control designs. However, GWAS findings may be confounded by population stratification if cases and controls are inadvertently drawn from different genetic backgrounds. In addition, since these loci were identified in cases with predominantly sporadic disease, little is known about their relationships with hereditary prostate cancer (HPC). The association between seventeen reported PCa susceptibility loci was evaluated with a family-based association test using 1,979 hereditary PCa families of European descent collected by members of the International Consortium for Prostate Cancer Genetics, with a total of 5,730 affected men. The risk alleles for 8 of the 17 loci were significantly over-transmitted from parents to affected offspring, including SNPs residing in 8q24 (regions 1, 2 and 3), 10q11, 11q13, 17q12 (region 1), 17q24 and Xp11. In subgroup analyses, three loci, at 8q24 (regions 1 and 2) plus 17q12, were significantly over-transmitted in hereditary PCa families with five or more affected members, while loci at 3p12, 8q24 (region 2), 11q13, 17q12 (region 1), 17q24 and Xp11 were significantly over-transmitted in HPC families with an average age of diagnosis at 65 years or less. Our results indicate that at least a subset of PCa risk-related loci identified by case-control GWAS are also associated with disease risk in HPC families.

    View details for DOI 10.1007/s00439-011-1136-0

    View details for Web of Science ID 000305195400008

    View details for PubMedID 22198737

  • Analysis of Xq27-28 linkage in the international consortium for prostate cancer genetics (ICPCG) families BMC MEDICAL GENETICS Bailey-Wilson, J. E., Childs, E. J., Cropp, C. D., Schaid, D. J., Xu, J., Camp, N. J., Cannon-Albright, L. A., Farnham, J. M., George, A., Powell, I., Carpten, J. D., Giles, G. G., Hopper, J. L., Severi, G., English, D. R., Foulkes, W. D., Maehle, L., Moller, P., Eeles, R., Easton, D., Guy, M., Edwards, S., Badzioch, M. D., Whittemore, A. S., Oakley-Girvan, I., Hsieh, C., Dimitrov, L., Stanford, J. L., Karyadi, D. M., Deutsch, K., McIntosh, L., Ostrander, E. A., Wiley, K. E., Isaacs, S. D., Walsh, P. C., Thibodeau, S. N., McDonnell, S. K., Hebbring, S., Lange, E. M., Cooney, K. A., Tammela, T. L., Schleutker, J., Maier, C., Bochum, S., Hoegel, J., Gronberg, H., Wiklund, F., Emanuelsson, M., Cancel-Tassin, G., Valeri, A., Cussenot, O., Isaacs, W. B. 2012; 13


    Genetic variants are likely to contribute to a portion of prostate cancer risk. Full elucidation of the genetic etiology of prostate cancer is difficult because of incomplete penetrance and genetic and phenotypic heterogeneity. Current evidence suggests that genetic linkage to prostate cancer has been found on several chromosomes including the X; however, identification of causative genes has been elusive.Parametric and non-parametric linkage analyses were performed using 26 microsatellite markers in each of 11 groups of multiple-case prostate cancer families from the International Consortium for Prostate Cancer Genetics (ICPCG). Meta-analyses of the resultant family-specific linkage statistics across the entire 1,323 families and in several predefined subsets were then performed.Meta-analyses of linkage statistics resulted in a maximum parametric heterogeneity lod score (HLOD) of 1.28, and an allele-sharing lod score (LOD) of 2.0 in favor of linkage to Xq27-q28 at 138 cM. In subset analyses, families with average age at onset less than 65 years exhibited a maximum HLOD of 1.8 (at 138 cM) versus a maximum regional HLOD of only 0.32 in families with average age at onset of 65 years or older. Surprisingly, the subset of families with only 2-3 affected men and some evidence of male-to-male transmission of prostate cancer gave the strongest evidence of linkage to the region (HLOD = 3.24, 134 cM). For this subset, the HLOD was slightly increased (HLOD = 3.47 at 134 cM) when families used in the original published report of linkage to Xq27-28 were excluded.Although there was not strong support for linkage to the Xq27-28 region in the complete set of families, the subset of families with earlier age at onset exhibited more evidence of linkage than families with later onset of disease. A subset of families with 2-3 affected individuals and with some evidence of male to male disease transmission showed stronger linkage signals. Our results suggest that the genetic basis for prostate cancer in our families is much more complex than a single susceptibility locus on the X chromosome, and that future explorations of the Xq27-28 region should focus on the subset of families identified here with the strongest evidence of linkage to this region.

    View details for DOI 10.1186/1471-2350-13-46

    View details for Web of Science ID 000311143100001

    View details for PubMedID 22712434

    View details for PubMedCentralID PMC3495053

  • Quality of life of younger breast cancer survivors: persistence of problems and sense of well-being PSYCHO-ONCOLOGY Bloom, J. R., Stewart, S. L., Oakley-Girvan, I., Banks, P. J., Shema, S. 2012; 21 (6): 655-665


    Ten years after diagnosis, women diagnosed with breast cancer at age 50 or younger were assessed to determine whether quality of life (QOL) problems found at five years persisted. We predicted that QOL in the physical and social domains would be poorer, but improvements would be found in the psychological domain.We re-interviewed 312 women, who had been interviewed at their five year anniversary and remained cancer free, on their QOL in three domains (physical, social, and psychological). Comparisons between their 5- and 10-year reports were performed using paired t-tests for numeric variables and McNemar's test for categorical variables. Multiple regression analysis was used to model change from 5 to 10 years in each QOL domain, given the level of QOL at 5 years.The women's mean age was 55, 60% were college graduates, 79% had a partner, and 27% were non-Euro-American. Ten years after diagnosis they reported poorer general health (p<0.0001) and physical well-being (p = 0.001), less sexual activity (p = 0.009), and more chronic conditions (p<0.0001) than at 5 years. Relationships were found between: (1) the number of chronic conditions at 5 years and decreased physical, social, and psychological well-being at 10 years; and (2) a smaller social network at 5 years and poorer social functioning at 10 years.Certain aspects of both physical and social QOL worsened over time. The remaining question is whether these changes can be attributed to the late effects of treatment or to normal effects of aging.

    View details for DOI 10.1002/pon.1965

    View details for Web of Science ID 000304813800011

    View details for PubMedID 21538677

  • Chromosomes 4 and 8 implicated in a genome wide SNP linkage scan of 762 prostate cancer families collected by the ICPCG PROSTATE Lu, L., Cancel-Tassin, G., Valeri, A., Cussenot, O., Lange, E. M., Cooney, K. A., Farnham, J. M., Camp, N. J., Cannon-Albright, L. A., Tammela, T. L., Schleutker, J., Hoegel, J., Herkommer, K., Maier, C., Vogel, W., Wiklund, F., Emanuelsson, M., Groenberg, H., Wiley, K. E., Isaacs, S. D., Walsh, P. C., Helfand, B. T., Kan, D., Catalona, W. J., Stanford, J. L., FitzGerald, L. M., Johanneson, B., Deutsch, K., McIntosh, L., Ostrander, E. A., Thibodeau, S. N., McDonnell, S. K., Hebbring, S., Schaid, D. J., Whittemore, A. S., Oakley-Girvan, I., Hsieh, C., Powell, I., Bailey-Wilson, J. E., Cropp, C. D., Simpson, C., Carpten, J. D., Seminara, D., Zheng, S. L., Xu, J., Giles, G. G., Severi, G., Hopper, J. L., English, D. R., Foulkes, W. D., Maehle, L., Moller, P., Badzioch, M. D., Edwards, S., Guy, M., Eeles, R., Easton, D., Isaacs, W. B. 2012; 72 (4): 410-426


    In spite of intensive efforts, understanding of the genetic aspects of familial prostate cancer (PC) remains largely incomplete. In a previous microsatellite-based linkage scan of 1,233 PC families, we identified suggestive evidence for linkage (i.e., LOD ≥ 1.86) at 5q12, 15q11, 17q21, 22q12, and two loci on 8p, with additional regions implicated in subsets of families defined by age at diagnosis, disease aggressiveness, or number of affected members.In an attempt to replicate these findings and increase linkage resolution, we used the Illumina 6000 SNP linkage panel to perform a genome-wide linkage scan of an independent set of 762 multiplex PC families, collected by 11 International Consortium for Prostate Cancer Genetics (ICPCG) groups.Of the regions identified previously, modest evidence of replication was observed only on the short arm of chromosome 8, where HLOD scores of 1.63 and 3.60 were observed in the complete set of families and families with young average age at diagnosis, respectively. The most significant linkage signals found in the complete set of families were observed across a broad, 37 cM interval on 4q13-25, with LOD scores ranging from 2.02 to 2.62, increasing to 4.50 in families with older average age at diagnosis. In families with multiple cases presenting with more aggressive disease, LOD scores over 3.0 were observed at 8q24 in the vicinity of previously identified common PC risk variants, as well as MYC, an important gene in PC biology.These results will be useful in prioritizing future susceptibility gene discovery efforts in this common cancer.

    View details for DOI 10.1002/pros.21443

    View details for Web of Science ID 000299159000007

    View details for PubMedID 21748754

    View details for PubMedCentralID PMC3568777

  • Complementary and alternative medicine use among newly diagnosed prostate cancer patients SUPPORTIVE CARE IN CANCER McDermott, C. L., Blough, D. K., Fedorenko, C. R., Arora, N. K., Zeliadt, S. B., Fairweather, M. E., Oakley-Girvan, I., Van Den Eeden, S. K., Ramsey, S. D. 2012; 20 (1): 65-73


    We surveyed prostate cancer patients about complementary and alternative medicine (CAM) use and evaluated patient factors that correlated with CAM use 6 months following diagnosis.The Prostate CAncer Therapy Selection study was a prospective, observational multi-site study of men's treatment decision-making process after a diagnosis of local stage prostate cancer. Recruitment occurred in community urology practices in Washington State, hospital-based urology clinics affiliated with the University of Southern California, and Kaiser Permanente in Northern California. Eligible study participants included men over age 21 diagnosed with local stage prostate cancer between May 1, 2005 and December 31, 2006.Fifty-two percent of survey respondents (379) reported using one or more types of CAM. Of the patients, 51% used one CAM method, 26% used two methods, and 23% used three or more methods. The most commonly reported category was mind-body therapies (65%). Only 43% of patients discussed their CAM use with a health professional; of those, 20% informed their primary care physician and 30% told the doctor managing their prostate cancer care. Less than half thought the CAM they used was "very helpful", but a majority thought it was somewhat helpful for their condition.Further research is needed to characterize the goals prostate cancer patients have for CAM, whether the treatments met those goals, and how this translates into the perceived helpfulness of these therapies. The implications of patients not discussing CAM use with health professionals at the time of prostate cancer treatment need further studies.

    View details for DOI 10.1007/s00520-010-1055-y

    View details for Web of Science ID 000297543200007

    View details for PubMedID 21120540

  • Double Jeopardy? Age, Race, and HRQOL in Older Adults with Cancer. Journal of cancer epidemiology Bellizzi, K. M., Aziz, N. M., Rowland, J. H., Weaver, K., Arora, N. K., Hamilton, A. S., Oakley-Girvan, I., Keel, G. 2012; 2012: 478642-?


    Understanding the post-treatment physical and mental function of older adults from ethnic/racial minority backgrounds with cancer is a critical step to determine the services required to serve this growing population. The double jeopardy hypothesis suggests being a minority and old could have compounding effects on health. This population-based study examined the physical and mental function of older adults by age (mean age = 75.7, SD = 6.1), ethnicity/race, and cancer (breast, prostate, colorectal, and gynecologic) as well as interaction effects between age, ethnicity/race and HRQOL. There was evidence of a significant age by ethnicity/race interaction in physical function for breast, prostate and all sites combined, but the interaction became non-significant (for breast and all sites combined) when comorbidity was entered into the model. The interaction persisted in the prostate cancer group after controlling for comorbidity, such that African Americans and Asian Americans in the 75-79 age group report lower physical health than non-Hispanic Whites and Hispanic Whites in this age group. The presence of double jeopardy in the breast and all sites combined group can be explained by a differential comorbid burden among the older (75-79) minority group, but the interaction found in prostate cancer survivors does not reflect this differential comorbid burden.

    View details for DOI 10.1155/2012/478642

    View details for PubMedID 22888348

  • Assessment of Quality of Cancer-Related Follow-Up Care From the Cancer Survivor's Perspective JOURNAL OF CLINICAL ONCOLOGY Arora, N. K., Reeve, B. B., Hays, R. D., Clauser, S. B., Oakley-Girvan, I. 2011; 29 (10): 1280-1289


    We assessed cancer survivors' perceptions of the quality of their follow-up care.We surveyed a population-based cohort of leukemia, bladder, and colorectal cancer survivors diagnosed 2 to 5 years previously in northern California (N = 623; participation rate, 69.2%; overall response rate, 49.2%). Data were collected between April 2003 and November 2004. Ten scales assessed survivors' perceptions of different aspects of care in the last 12 months, and an eleventh scale measured their overall ratings of care.On nine of the 11 scales, mean scores ranged from 88 to 97 on a 0 to 100 response format, indicating very positive experiences. The two areas where quality perceptions were lower were discussions about health promotion and the physician's knowledge of the whole patient. In adjusted analyses, those without private health insurance (P = .02) and Hispanic and Asian survivors compared with whites (P < .001) reported worse timeliness of care. Survivors who had multiple comorbidities reported better scores on timeliness of care (P < .01) and physicians' knowledge (P = .05) than survivors without any comorbidity. Length of the patient-physician relationship was the variable most consistently found to be significantly associated with survivors' quality assessments. Physicians' information exchange had the strongest relationship with overall ratings of care, followed by physicians' affective behavior, their knowledge of the survivor, and survivors' perceptions of coordination of care (P < .001 for all).Delivery of quality follow-up care to cancer survivors may require efforts to improve patient-centered communication and coordination. Special emphasis may need to be placed on health promotion discussions and adoption of a whole-person orientation.

    View details for DOI 10.1200/JCO.2010.32.1554

    View details for Web of Science ID 000288990100024

    View details for PubMedID 21357781

  • Patient Recruitment Methods to Evaluate Treatment Decision Making for Localized Prostate Cancer AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS Zeliadt, S. B., Ramsey, S. D., Van Den Eeden, S. K., Hamilton, A. S., Oakley-Girvan, I., Penson, D. F., Fairweather, M. E., Arora, N. K., Potosky, A. L. 2010; 33 (4): 381-386


    To examine methods for identifying and recruiting prostate cancer patients prior to initiating treatment to gain insight into the treatment decision process and avoid recall bias.One recruitment strategy involved providers and nursing staff approaching patients in community and academic urology clinics. The second recruitment strategy used electronic pathology reports to identify newly diagnosed cases in real time in an integrated health system. Our recruitment goal was to have patients complete the survey about the decision-making process prior to initiating therapy.The two recruitment methods yielded different response rates. Of the 226 eligible participants approached in urology clinics, 187 (83%) returned a completed baseline survey. Of the 1177 surveys mailed to potentially eligible participants at KPNC, 617 (52%) returned a completed baseline survey. The number of surveys completed prior to treatment was 125 (67%) for the clinic recruitment approach and 437 (71%) for the electronic medical record approach. Younger participants and patients with less aggressive clinical characteristics were more likely to complete the survey before initiating treatment. Other patient demographic and clinical factors were not associated with the timing of survey return.Recruiting newly diagnosed patients prior to initiating treatment is feasible with both approach methods. The use of electronic medical records to identify subjects was more cost efficient, although it results in a lower response rate.

    View details for DOI 10.1097/COC.0b013e3181b215d5

    View details for Web of Science ID 000280666200011

    View details for PubMedID 20010079

  • Unanticipated and Underappreciated Outcomes During Management of Local Stage Prostate Cancer: A Prospective Survey JOURNAL OF UROLOGY Ramsey, S. D., Zeliadt, S. B., Arora, N. K., Blough, D. K., Penson, D. F., Oakley-Girvan, I., Hamilton, A. S., Van Den Eeden, S. K., Fedorenko, C. R., Potosky, A. L. 2010; 184 (1): 120-125


    Due to the complexity of factors that must be considered when choosing a therapy for prostate cancer, we hypothesized that many men will find that certain factors such as side effects gain or lose importance after therapy relative to their expectations before therapy.We conducted a prospective survey of men deciding on a therapy for local stage prostate cancer in 3 geographic regions. Men were asked to rate the importance of 11 personal factors before starting therapy and again 6 months after therapy.Among 448 eligible men completing the most common treatment options, overall satisfaction with treatment choice was high across all therapies. While most men changed rankings of importance in at least 1 of the 11 factors, the majority of pre-post evaluations were highly consistent. In adjusted analyses the 2 factors that emerged as significantly underappreciated for all major prostate cancer treatments were 1) the impact of treatment on usual daily activities, and 2) the recommendations of friends and relatives who were affected with prostate cancer.Initial patient expectations of the importance of the majority of factors related to prostate cancer treatment are generally accurate. Better counseling may improve the accuracy of patient expectations of the personal burden of treatment, and their evaluation of the advice of affected friends and relatives.

    View details for DOI 10.1016/j.juro.2010.03.023

    View details for Web of Science ID 000278642300040

    View details for PubMedID 20478590

  • Genome-Wide Linkage Analysis of 1,233 Prostate Cancer Pedigrees From the International Consortium for Prostate Cancer Genetics Using Novel sum LINK and sum LOD Analyses PROSTATE Christensen, G. B., Baffoe-Bonnie, A. B., George, A., Powell, I., Bailey-Wilson, J. E., Carpten, J. D., Giles, G. G., Hopper, J. L., Seven, G., English, D. R., Foulkes, W. D., Maehle, L., Moller, P., Eeles, R., Easton, D., Badzioch, M. D., Whittemore, A. S., Oakley-Girvan, I., Hsieh, C., Dimitrov, L., Xu, J., Stanford, J. L., Johanneson, B., Deutsch, K., McIntosh, L., Ostrander, E. A., Wiley, K. E., Isaacs, S. D., Walsh, P. C., Isaacs, W. B., Thibodeau, S. N., McDonnell, S. K., Hebbring, S., Schaid, D. J., Lange, E. M., Cooney, K. A., Tammela, T. L., Schleutker, J., Paiss, T., Maier, C., Gronberg, H., Wiklund, F., Emanuelsson, M., Farnham, J. M., Cannon-Albright, L. A., Camp, N. J. 2010; 70 (7): 735-744


    Prostate cancer (PC) is generally believed to have a strong inherited component, but the search for susceptibility genes has been hindered by the effects of genetic heterogeneity. The recently developed sumLINK and sumLOD statistics are powerful tools for linkage analysis in the presence of heterogeneity.We performed a secondary analysis of 1,233 PC pedigrees from the International Consortium for Prostate Cancer Genetics (ICPCG) using two novel statistics, the sumLINK and sumLOD. For both statistics, dominant and recessive genetic models were considered. False discovery rate (FDR) analysis was conducted to assess the effects of multiple testing.Our analysis identified significant linkage evidence at chromosome 22q12, confirming previous findings by the initial conventional analyses of the same ICPCG data. Twelve other regions were identified with genome-wide suggestive evidence for linkage. Seven regions (1q23, 5q11, 5q35, 6p21, 8q12, 11q13, 20p11-q11) are near loci previously identified in the initial ICPCG pooled data analysis or the subset of aggressive PC pedigrees. Three other regions (1p12, 8p23, 19q13) confirm loci reported by others, and two (2p24, 6q27) are novel susceptibility loci. FDR testing indicates that over 70% of these results are likely true positive findings. Statistical recombinant mapping narrowed regions to an average of 9 cM.Our results represent genomic regions with the greatest consistency of positive linkage evidence across a very large collection of high-risk PC pedigrees using new statistical tests that deal powerfully with heterogeneity. These regions are excellent candidates for further study to identify PC predisposition genes.

    View details for DOI 10.1002/pros.21106

    View details for Web of Science ID 000277338800006

    View details for PubMedID 20333727

    View details for PubMedCentralID PMC3428045

  • Physicians' decision-making style and psychosocial outcomes among cancer survivors PATIENT EDUCATION AND COUNSELING Arora, N. K., Weaver, K. E., Clayman, M. L., Oakley-Girvan, I., Potosky, A. L. 2009; 77 (3): 404-412


    We evaluated pathways linking physicians' decision-making style with cancer survivors' health-related quality of life (HRQOL).We analyzed survey data from 623 survivors diagnosed with leukemia, colorectal, or bladder cancer in Northern California, 2-5 years prior to the study. Of these, 395 reported making a medical decision in the past 12 months and were asked about their physician's decision-making style. We evaluated the association of physician style with proximal communication outcomes (trust and participation self-efficacy), intermediate cognitive outcomes (perceived control and uncertainty), and distal health outcomes (physical and mental HRQOL).Overall, 54% of survivors reported a sub-optimal decision-making style for their physician. With the exception of physical health, physician style was associated with all proximal, intermediate, and distal outcomes (p< or =0.01). We identified two significant pathways by which a participatory physician style may be associated with survivors' mental health: (1) by increasing survivors' participation self-efficacy and thereby enhancing their perceptions of personal control (p<0.01); (2) by enhancing survivors' level of trust and thereby reducing their perceptions of uncertainty (p<0.05).A participatory physician style may improve survivors' mental health by a complex two-step mechanism of improving survivors' proximal communication and intermediate cognitive outcomes.Physicians who adopt a participatory decision-making style are likely to facilitate patient empowerment and enhance patients' HRQOL.

    View details for DOI 10.1016/j.pec.2009.10.004

    View details for Web of Science ID 000273158600013

    View details for PubMedID 19892508

  • Follow-up care delivery among colorectal cancer survivors most often seen by primary and subspecialty care physicians. Journal of general internal medicine Haggstrom, D. A., Arora, N. K., Helft, P., Clayman, M. L., Oakley-Girvan, I. 2009; 24: S472-9


    The Institute of Medicine has identified patients as a key source of information for assessing the quality of care.To evaluate the association of physician specialty with the content and quality of follow-up cancer care.Three hundred three colorectal cancer (CRC) survivors in Northern California were surveyed 2-5 years post-diagnosis.Specialty of physician seen most often [primary care physician (PCP), oncologist, surgeon, or gastroenterologist]; other physician specialties seen; patient characteristics; content of visits; patient-centered quality of follow-up care (communication, coordination, nursing, and staff interactions).A minority (16%) of CRC survivors reported that the doctor they most often saw for follow-up cancer care was a PCP, while 60% saw an oncologist. Many CRC survivors (40%) saw >1 physician for follow-up cancer care. Survivors most often seen by PCPs were more likely to have three or more medical comorbidities (70% vs. 51%, p = 0.012) than survivors seen by subspecialty physicians. Survivors seen by PCPs were less likely to report seeing a doctor for medical tests and more likely to report discussing disease prevention (82% vs. 64%, p = 0.012) or diet (70% vs. 48%, p = 0.005) with their doctor. There were no significant specialty differences in patient-centered quality of follow-up cancer care.Cancer survivors' assessment of the quality of care was similar across specialties, while the content of follow-up cancer care varied by physician specialty. These findings provide important information about the potential value of primary care and the need for coordination when delivering care to CRC survivors.

    View details for DOI 10.1007/s11606-009-1017-6

    View details for PubMedID 19838853

  • Access to Information Sources and Treatment Considerations Among Men With Local Stage Prostate Cancer UROLOGY Ramsey, S. D., Zeliadt, S. B., Arora, N. K., Potosky, A. L., Blough, D. K., Hamilton, A. S., Van Den Eeden, S. K., Oakley-Girvan, I., Penson, D. F. 2009; 74 (3): 509-515


    To determine the role of information sources in the treatment decision-making process of men diagnosed with local stage prostate cancer. Diagnosed men have access to a large number of information sources about therapy, including print and broadcast media, the Internet, books, and friends with the disease.Prospective survey of men with local stage prostate cancer in 3 geographically separate regions was carried out. Most men were surveyed after diagnosis but before starting therapy.On average, men with local prostate cancer consulted nearly 5 separate sources of information before treatment. The most common source of information was the patient's physician (97%), followed by lay-literature (pamphlets, videos) (76%), other health professionals (71%), friends with prostate cancer (67%), and the Internet (58%). Most men rated the sources they consulted as helpful. Consulting the Internet was associated with considering more treatment options. Several information sources were significantly associated with considering particular treatments, but the magnitude of association was small in relation to patient age, comorbidity, and Gleason score. More than 70% of men stated that they were considering or planning only one type of therapy.Men with local stage prostate cancer consult a wide range of information sources. Nonphysician information sources appear to influence their treatment considerations, but to a smaller degree than clinical factors.

    View details for DOI 10.1016/j.urology.2009.01.090

    View details for Web of Science ID 000270207100011

    View details for PubMedID 19589564

  • Health-related information needs in a large and diverse sample of adult cancer survivors: implications for cancer care. Journal of cancer survivorship : research and practice Beckjord, E. B., Arora, N. K., McLaughlin, W., Oakley-Girvan, I., Hamilton, A. S., Hesse, B. W. 2008; 2 (3): 179-189


    This study describes the information needs of adult cancer survivors, identifies sociodemographic, health, and healthcare-related factors associated with information needs, and examines the relationship between information needs and survivors' perceived mental and physical health.One thousand forty survivors 2-5 years post-diagnosis who were identified via two cancer registries were included in the present analysis. Self-report questionnaires assessed six categories of information needs, sociodemographic, health, and healthcare-related variables, and perceived mental and physical health.Information needs were prevalent and varied; most survivors need more information about tests and treatments, health promotion, side effects and symptoms, and interpersonal and emotional issues. Multivariate analyses suggested that survivors who were younger, who reported non-White race/ethnicity, who reported less than excellent quality of follow-up cancer care, and who had more comorbid health conditions had more information needs. After adjustment for sociodemographic and health-related variables, more information needs were associated with worse perceived mental and physical health.Most cancer survivors needed more information about maintaining good health outcomes during survivorship. Health communication interventions, such as Survivorship Care Plans, have excellent potential to address survivors' information needs while improving quality of follow-up cancer care and health-related quality of life.

    View details for DOI 10.1007/s11764-008-0055-0

    View details for PubMedID 18792791

  • Association of Preexisting Symptoms with Treatment Decisions among Newly Diagnosed Prostate Cancer Patients. The patient Zeliadt, S. B., Ramsey, S. D., Potosky, A. L., Arora, N. K., Blough, D. K., Oakley-Girvan, I., Hamilton, A. S., Van Den Eeden, S. K., Penson, D. F. 2008; 1 (3): 189


    BACKGROUND: The choice between surgical versus non-surgical treatment options is a fundamental decision for men with local stage prostate cancer because of differences in risks of genitourinary side effects among available treatments. OBJECTIVES: We assessed whether preexisting genitourinary symptoms at the time of diagnosis influenced men's preferences for surgery versus other management options. METHODS: We recruited 593 patients with newly diagnosed local stage prostate cancer prior to initiating treatment from an integrated health care system, an academic urology center, and community urology clinics. Using logistic regression we compared whether men had a preference for non-surgical options or only preferred surgery. RESULTS: Nearly 60% indicated they were considering non-surgical options. Age and clinical characteristics but not preexisting genitourinary symptoms influenced the decision between preferences for surgical or non-surgical options. A total of 62% of men reported side effects as a main factor in their treatment decision. Men with more aggressive tumor types were less likely to consider side effects, however, men who reported poor ability to have an erection were more likely to consider side effects (p<0.001). CONCLUSION: Sexual dysfunction at time of diagnosis, but not other genitourinary symptoms, is associated with men considering treatment-related side effects when considering surgery versus other options. Men who are not experiencing sexual dysfunction at diagnosis may discount the risks of side effects in the decision making process.

    View details for DOI 10.2165/1312067-200801030-00006

    View details for PubMedID 20119493

    View details for PubMedCentralID PMC2812903

  • Prostate cancer risk in relation to insulin-like growth factor (IGF)-I and IGF-binding protein-3: A prospective multiethnic study CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Borugian, M. J., Spinelli, J. J., Sun, Z., Kolonel, L. N., Oakley-Girvan, I., Pollak, M. D., Whittemore, A. S., Wu, A. H., Gallagher, R. P. 2008; 17 (1): 252-254
  • Contribution of BRCA1 and BRCA2 mutations to inherited ovarian cancer HUMAN MUTATION Ramus, S. J., Harrington, P. A., Pye, C., DiCioccio, R. A., Cox, M. J., Garlinghouse-Jones, K., Oakley-Girvan, I., Jacobs, I. J., Hardy, R. M., Whittemore, A. S., Ponder, B. A., Piver, M. S., Pharoah, P. D., Gayther, S. A. 2007; 28 (12): 1207-1215


    A total of 283 epithelial ovarian cancer families from the United Kingdom (UK) and the United States (US) were screened for coding sequence changes and large genomic alterations (rearrangements and deletions) in the BRCA1 and BRCA2 genes. Deleterious BRCA1 mutations were identified in 104 families (37%) and BRCA2 mutations in 25 families (9%). Of the 104 BRCA1 mutations, 12 were large genomic alterations; thus this type of change represented 12% of all BRCA1 mutations. Six families carried a previously described exon 13 duplication, known to be a UK founder mutation. The remaining six BRCA1 genomic alterations were previously unreported and comprised five deletions and an amplification of exon 15. One of the 25 BRCA2 mutations identified was a large genomic deletion of exons 19-20. The prevalence of BRCA1/2 mutations correlated with the extent of ovarian and breast cancer in families. Of 37 families containing more than two ovarian cancer cases and at least one breast cancer case with diagnosis at less than 60 years of age, 30 (81%) had a BRCA1/2 mutation. The mutation prevalence was appreciably less in families without breast cancer; mutations were found in only 38 out of 141 families (27%) containing two ovarian cancer cases only, and in 37 out of 59 families (63%) containing three or more ovarian cancer cases. These data indicate that BRCA1 and BRCA2 are the major susceptibility genes for ovarian cancer but that other susceptibility genes may exist. Finally, it is likely that these data will be of clinical importance for individuals in families with a history of epithelial ovarian cancer, in providing accurate estimates of their disease risks.

    View details for DOI 10.1002/humu.20599

    View details for Web of Science ID 000251534700008

    View details for PubMedID 17688236

  • Prediagnostic C-peptide and risk of prostate cancer CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Borugian, M. J., Spinelli, J. J., Sun, Z., Kolonel, L. N., Oakley-Girvan, I., Pollak, M. D., Whittemore, A. S., Wu, A. H., Gallagher, R. P. 2007; 16 (10): 2164-2165
  • Compelling evidence for a prostate cancer gene at 22q12.3 by the International Consortium for Prostate Cancer Genetics HUMAN MOLECULAR GENETICS Camp, N. J., Cannon-Albright, L. A., Farnham, J. M., Baffoe-Bonnie, A. B., George, A., Powell, I., Bailey-Wilson, J. E., Carpten, J. D., Giles, G. G., Hopper, J. L., Severi, G., English, D. R., Foulkes, W. D., Maehle, L., Moller, P., Eeles, R., Easton, D., Badzioch, M. D., Whittemore, A. S., Oakley-Girvan, I., Hsieh, C., Dimitrov, L., Xu, J., Stanford, J. L., Johanneson, B., Deutsch, K., McIntosh, L., Ostrander, E. A., Wiley, K. E., Isaacs, S. D., Walsh, P. C., Thibodeau, S. N., McDonnell, S. K., Hebbring, S., Schaid, D. J., Lange, E. M., Cooney, K. A., Tammela, T. L., Schleutker, J., Paiss, T., Maier, C., Gronberg, H., Wiklund, F., Emanuelsson, M., Isaacs, W. B. 2007; 16 (11): 1271-1278


    Previously, an analysis of 14 extended, high-risk Utah pedigrees localized in the chromosome 22q linkage region to 3.2 Mb at 22q12.3-13.1 (flanked on each side by three recombinants) contained 31 annotated genes. In this large, multi-centered, collaborative study, we performed statistical recombinant mapping in 54 pedigrees selected to be informative for recombinant mapping from nine member groups of the International Consortium for Prostate Cancer Genetics (ICPCG). These 54 pedigrees included the 14 extended pedigrees from Utah and 40 pedigrees from eight other ICPCG member groups. The additional 40 pedigrees were selected from a total pool of 1213 such that each pedigree was required to contain both at least four prostate cancer (PRCA) cases and exhibit evidence for linkage to the chromosome 22q region. The recombinant events in these 40 independent pedigrees confirmed the previously proposed region. Further, when all 54 pedigrees were considered, the three-recombinant consensus region was narrowed down by more than a megabase to 2.2 Mb at chromosome 22q12.3 flanked by D22S281 and D22S683. This narrower region eliminated 20 annotated genes from that previously proposed, leaving only 11 genes. This region at 22q12.3 is the most consistently identified and smallest linkage region for PRCA. This collaborative study by the ICPCG illustrates the value of consortium efforts and the continued utility of linkage analysis using informative pedigrees to localize genes for complex diseases.

    View details for DOI 10.1093/hmg/ddm075

    View details for Web of Science ID 000248053300001

    View details for PubMedID 17478474

    View details for PubMedCentralID PMC2653215

  • Multiple regions within 8q24 independently affect risk for prostate cancer NATURE GENETICS Haiman, C. A., Patterson, N., Freedman, M. L., Myers, S. R., Pike, M. C., Waliszewska, A., Neubauer, J., Tandon, A., Schirmer, C., McDonald, G. J., Greenway, S. C., Stram, D. O., Le Marchand, L., Kolonel, L. N., Frasco, M., Wong, D., Pooler, L. C., Ardlie, K., Oakley-Girvan, I., Whittemore, A. S., Cooney, K. A., John, E. M., Ingles, S. A., Altshuler, D., Henderson, B. E., Reich, D. 2007; 39 (5): 638-644


    After the recent discovery that common genetic variation in 8q24 influences inherited risk of prostate cancer, we genotyped 2,973 SNPs in up to 7,518 men with and without prostate cancer from five populations. We identified seven risk variants, five of them previously undescribed, spanning 430 kb and each independently predicting risk for prostate cancer (P = 7.9 x 10(-19) for the strongest association, and P < 1.5 x 10(-4) for five of the variants, after controlling for each of the others). The variants define common genotypes that span a more than fivefold range of susceptibility to cancer in some populations. None of the prostate cancer risk variants aligns to a known gene or alters the coding sequence of an encoded protein.

    View details for DOI 10.1038/ng2015

    View details for Web of Science ID 000245971300019

    View details for PubMedID 17401364

  • Pooled genome linkage scan of aggressive prostate cancer: results from the International Consortium for Prostate Cancer Genetics HUMAN GENETICS Schaid, D. J. 2006; 120 (4): 471-485


    While it is widely appreciated that prostate cancers vary substantially in their propensity to progress to a life-threatening stage, the molecular events responsible for this progression have not been identified. Understanding these molecular mechanisms could provide important prognostic information relevant to more effective clinical management of this heterogeneous cancer. Hence, through genetic linkage analyses, we examined the hypothesis that the tendency to develop aggressive prostate cancer may have an important genetic component. Starting with 1,233 familial prostate cancer families with genome scan data available from the International Consortium for Prostate Cancer Genetics, we selected those that had at least three members with the phenotype of clinically aggressive prostate cancer, as defined by either high tumor grade and/or stage, resulting in 166 pedigrees (13%). Genome-wide linkage data were then pooled to perform a combined linkage analysis for these families. Linkage signals reaching a suggestive level of significance were found on chromosomes 6p22.3 (LOD = 3.0), 11q14.1-14.3 (LOD = 2.4), and 20p11.21-q11.21 (LOD = 2.5). For chromosome 11, stronger evidence of linkage (LOD = 3.3) was observed among pedigrees with an average at diagnosis of 65 years or younger. Other chromosomes that showed evidence for heterogeneity in linkage across strata were chromosome 7, with the strongest linkage signal among pedigrees without male-to-male disease transmission (7q21.11, LOD = 4.1), and chromosome 21, with the strongest linkage signal among pedigrees that had African American ancestry (21q22.13-22.3; LOD = 3.2). Our findings suggest several regions that may contain genes which, when mutated, predispose men to develop a more aggressive prostate cancer phenotype. This provides a basis for attempts to identify these genes, with potential clinical utility for men with aggressive prostate cancer and their relatives.

    View details for DOI 10.1007/s00439-006-0219-9

    View details for Web of Science ID 000241791900003

    View details for PubMedID 16932970

  • Family history, perceived risk, and prostate cancer screening among African American men CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Bloom, J. R., Stewart, S. L., Oakley-Girvans, I., Banks, P. J., Chang, S. 2006; 15 (11): 2167-2173


    Many African American men have two major risk factors for prostate cancer. By ethnicity alone, they have twice the risk of Euro-American men of developing prostate cancer. Having a family history (brother or father with prostate cancer) also doubles their risk. The major hypotheses tested in this study are that men with a family history perceive their risk to be higher, are more worried about getting prostate cancer, and are more likely to have used cancer screening tests than men without such a history.A sample of 208 African American men, ages 40 to 74 years, were recruited through relatives or friends whose prostate cancer diagnosis was reported to the California Cancer Registry during the years 1997 to 2001 and from churches and African American social groups. Following a screening interview to determine eligibility, 88 men with self-reported, first-degree family history of prostate cancer and 120 without such history were interviewed by telephone. Logistic regression was used to create models of perceived risk, prostate cancer worries, receipt of a digital rectal exam, and/or prostate-specific antigen (PSA) testing.Men with a self-reported family history of prostate cancer did not perceive their risk as higher than men without a family history, nor did they report more cancer worries. They were more likely to report having a recent PSA test, but not a digital rectal exam. Having a higher than average perceived risk was associated with younger age, a college education, and lower mental well-being, and reporting more prostate cancer worries and being more likely to have had a recent PSA test.Although there continues to be controversy about PSA testing, these data suggest that African American men at above-average risk are inclined to be screened.

    View details for DOI 10.1158/1055-9965.EPI-05-0738

    View details for Web of Science ID 000242150300027

    View details for PubMedID 17119042

  • Admixture mapping identifies 8q24 as a prostate cancer risk locus in African-American men PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Freedman, M. L., Haiman, C. A., Patterson, N., McDonald, G. J., Tandon, A., Waliszewska, A., Penney, K., Steen, R. G., Ardlie, K., John, E. M., Clakley-Girvan, I., Whitternore, A. S., Cooney, K. A., Ingles, S. A., Altshuler, D., Henderson, B. E., Reich, D. 2006; 103 (38): 14068-14073


    A whole-genome admixture scan in 1,597 African Americans identified a 3.8 Mb interval on chromosome 8q24 as significantly associated with susceptibility to prostate cancer [logarithm of odds (LOD) = 7.1]. The increased risk because of inheriting African ancestry is greater in men diagnosed before 72 years of age (P < 0.00032) and may contribute to the epidemiological observation that the higher risk for prostate cancer in African Americans is greatest in younger men (and attenuates with older age). The same region was recently identified through linkage analysis of prostate cancer, followed by fine-mapping. We strongly replicated this association (P < 4.2 x 10(-9)) but find that the previously described alleles do not explain more than a fraction of the admixture signal. Thus, admixture mapping indicates a major, still-unidentified risk gene for prostate cancer at 8q24, motivating intense work to find it.

    View details for DOI 10.1073/pnas.0605832103

    View details for Web of Science ID 000240746600031

    View details for PubMedID 16945910

  • A combined genomewide linkage scan of 1,233 families for prostate cancer-susceptibility genes conducted by the international consortium for prostate cancer genetics AMERICAN JOURNAL OF HUMAN GENETICS Xu, J. F., Dimitrov, L., Chang, B. L., Adams, T. S., Turner, A. R., Meyers, D. A., Eeles, R. A., Easton, D. F., Foulkes, W. D., Simard, J., Giles, G. G., Hopper, J. L., Mahle, L., Moller, P., Bishop, T., Evans, C., Edwards, S., Meitz, J., Bullock, S., Hope, Q., Hsieh, C. L., Halpern, J., Balise, R. N., Oakley-Girvan, I., Whittemore, A. S., Ewing, C. M., Gielzak, M., Isaacs, S. D., Walsh, P. C., Wiley, K. E., Isaacs, W. B., Thibodeau, S. N., McDonnell, S. K., Cunningham, J. M., Zarfas, K. E., Hebbring, S., Schaid, D. J., Friedrichsen, D. M., Deutsch, K., Kolb, S., Badzioch, M., Jarvik, G. P., Janer, M., Hood, L., Ostrander, E. A., Stanford, J. L., Lange, E. M., Beebe-Dimmer, J. L., Mohai, C. E., Cooney, K. A., Ikonen, T., Baffoe-Bonnie, A., Fredriksson, H., Matikainen, M. P., Tammela, T. L., Bailey-Wilson, J., Schleutker, J., Maier, C., Herkommer, K., Hoegel, J. J., Vogel, W., Paiss, T., Wiklund, F., Emanuelsson, M., Stenman, E., Jonsson, B. A., Gronberg, H., Camp, N. J., Farnham, J., Cannon-Albright, L. A., Seminara, D. 2005; 77 (2): 219-229


    Evidence of the existence of major prostate cancer (PC)-susceptibility genes has been provided by multiple segregation analyses. Although genomewide screens have been performed in over a dozen independent studies, few chromosomal regions have been consistently identified as regions of interest. One of the major difficulties is genetic heterogeneity, possibly due to multiple, incompletely penetrant PC-susceptibility genes. In this study, we explored two approaches to overcome this difficulty, in an analysis of a large number of families with PC in the International Consortium for Prostate Cancer Genetics (ICPCG). One approach was to combine linkage data from a total of 1,233 families to increase the statistical power for detecting linkage. Using parametric (dominant and recessive) and nonparametric analyses, we identified five regions with "suggestive" linkage (LOD score >1.86): 5q12, 8p21, 15q11, 17q21, and 22q12. The second approach was to focus on subsets of families that are more likely to segregate highly penetrant mutations, including families with large numbers of affected individuals or early age at diagnosis. Stronger evidence of linkage in several regions was identified, including a "significant" linkage at 22q12, with a LOD score of 3.57, and five suggestive linkages (1q25, 8q13, 13q14, 16p13, and 17q21) in 269 families with at least five affected members. In addition, four additional suggestive linkages (3p24, 5q35, 11q22, and Xq12) were found in 606 families with mean age at diagnosis of < or = 65 years. Although it is difficult to determine the true statistical significance of these findings, a conservative interpretation of these results would be that if major PC-susceptibility genes do exist, they are most likely located in the regions generating suggestive or significant linkage signals in this large study.

    View details for Web of Science ID 000230387200004

    View details for PubMedID 15988677

  • Oral contraceptive use and ovarian cancer risk among carriers of BRCA1 or BRCA2 mutations BRITISH JOURNAL OF CANCER Whittemore, A. S., Balise, R. R., Pharoah, P. D., DiCioccio, R. A., Oakley-Girvan, I., Ramus, S. J., Daly, M., Usinowicz, M. B., Garlinghouse-Jones, K., Ponder, B. A., Buys, S., Senie, R., Andrulis, I., John, E., Hopper, J. L., Piver, M. S. 2004; 91 (11): 1911-1915


    Women with mutations of the genes BRCA1 or BRCA2 are at increased risk of ovarian cancer. Oral contraceptives protect against ovarian cancer in general, but it is not known whether they protect against the disease in carriers of these mutations. We obtained self-reported lifetime histories of oral contraceptive use from 451 women who carried mutations of BRCA1 or BRCA2. We used conditional logistic regression to estimate the odds ratios associated with oral contraceptive use, comparing the histories of 147 women with ovarian cancer (cases) to those of 304 women without ovarian cancer (controls) who were matched to cases on year of birth, country of residence and gene (BRCA1 vs BRCA2). Reference ages for controls had to exceed the ages at diagnosis of their matched cases. After adjusting for parity, the odds-ratio for ovarian cancer associated with use of oral contraceptives for at least 1 year was 0.85 (95 percent confidence interval, 0.53-1.36). The risk decreased by 5% (1-9%) with each year of use (P for trend=0.01). Use for 6 or more years was associated with an odds-ratio of 0.62 (0.35-1.09). These data support the hypothesis that long-term oral contraceptive use reduces the risk of ovarian cancer among women who carry mutations of BRCA1 or BRCA2.

    View details for DOI 10.1038/sj.bjc.6602239

    View details for Web of Science ID 000225301700010

    View details for PubMedID 15545966

    View details for PubMedCentralID PMC2410144

  • Risk of early-onset prostate cancer in relation to germ line polymorphisms of the vitamin D receptor CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Oakley-Girvan, I., Feldman, D., Eccleshall, T. R., Gallagher, R. P., Wu, A. H., Kolonel, L. N., Halpern, J., Balise, R. R., West, D. W., Paffenbarger, R. S., Whittemore, A. S. 2004; 13 (8): 1325-1330


    Vitamin D inhibits prostate cancer cell growth, angiogenesis, and metastasis. These actions are mediated by the vitamin D receptor. We examined associations between prostate cancer risk and five polymorphisms in the VDR gene: four single nucleotide polymorphisms (FokI, BsmI, ApaI, and TaqI restriction sites) and the polyadenylic acid microsatellite. Specifically, we genotyped population-based samples of young African Americans (113 cases and 121 controls) and Whites (232 cases and 171 controls) and members of 98 predominantly White families with multiple cases of prostate cancer. Among Whites, there was no evidence for association between prostate cancer risk and alleles at any of the five polymorphic sites regardless of how the men were ascertained. Moreover, estimated five-locus haplotype frequencies were similar in White cases and controls. Among African Americans, prostate cancer risk was associated with homozygosity for the F allele at the FokI site (odds ratio 1.9, 95% confidence interval 1.0-3.3). In addition, estimated haplotype frequencies differed significantly (P < 0.01) between African American cases and controls. These findings need replication in other studies of African Americans. Homozygosity for the F allele at the FokI site is more prevalent in the African American population than in U.S. Whites. If the FokI association noted here were causal, this difference could account for some of the disease burden among African Americans and some of the excess risk in African Americans compared with Whites.

    View details for Web of Science ID 000223155500010

    View details for PubMedID 15298953

  • Histopathology, FIGO stage, and BRCA mutation status of ovarian cancers from the Gilda Radner Familial Ovarian Cancer Registry INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY Werness, B. A., Ramus, S. J., DiCioccio, R. A., Whittemore, A. S., Garlinghouse-Jones, K., Oakley-Girvan, I., Tsukada, Y., Harrington, P., Gayther, S. A., Ponder, B. A., Piver, M. S. 2004; 23 (1): 29-34


    Studies of the histopathology of ovarian cancer arising in patients with germline mutations in BRCA1 or BRCA2 have shown inconsistent findings. We analyzed the large number of tumors from women enrolled in the Gilda Radner Familial Ovarian Cancer Registry for correlations between histopathology and BRCA mutation status. Histopathology slides and reports were reviewed for histology, grade, and stage for cancers of the ovary or peritoneum in 220 women from 126 Gilda Radner Familial Ovarian Cancer Registry families. At least one affected member of each family was analyzed for mutations in the BRCA1 and BRCA2 genes, and tumors from mutation-positive families were compared with those from mutation-negative families. Of 70 patients from 38 BRCA1-positive families, 69 had epithelial ovarian carcinoma and one had a dysgerminoma. Fifteen of 16 patients from nine BRCA2-positive families had epithelial ovarian cancer, and one had a primary peritoneal cancer. Of 134 patients from 79 BRCA-negative families, 118 had epithelial ovarian carcinoma, 11 had ovarian borderline tumors, three had nonepithelial tumors, and two had primary peritoneal carcinoma. There were fewer grade 1 (p < 0.001) and stage I (p = 0.005) cancers in patients from BRCA-positive families than in patients from BRCA-negative families. Neither mucinous nor borderline tumors were found in the BRCA-positive families. In conclusion, ovarian cancers arising in women from BRCA-positive families are more likely to be high-grade and have extraovarian spread than tumors arising in women from BRCA-negative families. Borderline and mucinous tumors do not appear to be part of the phenotype of families with germline mutations in the BRCA genes.

    View details for DOI 10.1097/

    View details for Web of Science ID 000187434700006

    View details for PubMedID 14668547

  • Stage at diagnosis and survival in a multiethnic cohort of prostate cancer patients AMERICAN JOURNAL OF PUBLIC HEALTH Oakley-Girvan, I., Kolonel, L. N., Gallagher, R. P., Wu, A. H., Felberg, A., Whittemore, A. S. 2003; 93 (10): 1753-1759


    We evaluated the effects of socioeconomic status and comorbidity on stage of disease and survival among 1509 population-based prostate cancer patients.We applied logistic regression and Cox proportional hazards regression to data from Whites, African Americans, and Asian Americans who were diagnosed from 1987 to 1991.Patients with existing comorbid conditions were less likely than those without these conditions to be diagnosed with advanced cancer. Compared with Whites, African Americans (odds ratio [OR] = 1.5; 95% confidence interval [CI] = 1.1, 2.2) and foreign-born Asian Americans (OR = 1.6; 95% CI = 1.0, 2.4) were more likely to be diagnosed with advanced cancer. Among men with localized disease, prostate cancer death rates were higher for African Americans than for Whites (death rate ratio = 2.3; 95% CI = 1.2, 4.7).These findings support the need for further investigation of factors that affect access to and use of health care among African Americans and Asian Americans.

    View details for Web of Science ID 000185881100031

    View details for PubMedID 14534233

    View details for PubMedCentralID PMC1448045

  • Segregation analysis of prostate cancer in 1719 white, African-American and Asian-American families in the United States and Canada CANCER CAUSES & CONTROL Gong, G., Oakley-Girvan, I., Wu, A. H., Kolonel, L. N., John, E. M., West, D. W., Felberg, A., Gallagher, R. P., Whittemore, A. S. 2002; 13 (5): 471-482


    Some data suggest that brothers of prostate cancer patients have higher disease risk than their fathers, supporting an X-linked or recessive mode of inheritance. However, higher observed frequencies in brothers than fathers may merely reflect the strong temporal changes in US incidence rates.(a) to evaluate the fit of X-linked, recessive, and dominant modes of inheritance to prostate cancer incidence, specific for calendar year, age, and race, in population-based samples of US and Canadian families; and (b) to evaluate a simple multifactorial model for familial aggregation of prostate cancer due to shared low-penetrance variants of many genes or shared lifestyle factors.The data consist of reported prostate cancer incidence in first-degree relatives of 1,719 white, African-American, and Asian-American men with and without prostate cancer at ages <70 years. Model parameters were estimated by maximizing a pseudo-likelihood function of the data, and goodness of model fit was assessed by evaluating discrepancies between observed and expected numbers of pairs of relatives with prostate cancer.After adjusting for temporal trends in prostate cancer incidence rates we found that the X-linked model fit poorly. underpredicting the observed number of affected father-son pairs. This also was true of the recessive model, although the evidence for poor fit did not achieve statistical significance. In contrast, the dominant model provided adequate fit to the data. In this model the race-specific penetrance estimates for carriers of deleterious genotypes were similar among African-Americans and whites, but lower among Asian-Americans: risk by age 80 years for carriers born in 1900 was estimated as 75.3% for African-Americans and whites, and 44.4% for Asian-Americans. None of the Mendelian models fit the data better than did the simple multifactorial model.The good fit of the multifactorial model suggests that multiple genes, each having low penetrance, may be responsible for most inherited prostate cancer susceptibility, and that the contribution of rare highly penetrant mutations is small.

    View details for Web of Science ID 000175947900010

    View details for PubMedID 12146852

  • A genome screen of families with multiple cases of prostate cancer: Evidence of genetic heterogeneity AMERICAN JOURNAL OF HUMAN GENETICS Hsieh, C. L., Oakley-Girvan, I., Balise, R. R., Halpern, J., Gallagher, R. P., Wu, A. H., Kolonel, L. N., O'Brien, L. E., Lin, I. P., Van den Berg, D. J., Teh, C. Z., West, D. W., Whittemore, A. S. 2001; 69 (1): 148-158


    We conducted a genomewide screen for prostate cancer-susceptibility genes on the basis of data from 98 families from the United States and Canada that had three or more verified diagnoses of prostate cancer among first- and second-degree relatives. We found a statistically significant excess of markers for which affected relatives exhibited modest amounts of excess allele-sharing; however, no single chromosomal region contained markers with excess allele-sharing of sufficient magnitude to indicate unequivocal evidence of linkage. Positive linkage signals of nominal statistical significance were found in two regions (5p-q and 12p) that have been identified as weakly positive in other data sets and in region 19p, which has not been identified previously. All these signals were considerably stronger for analyses restricted to families with mean age at onset below the median than for analyses of families with mean age at onset above the median. The data provided little support for any of the putative prostate cancer-susceptibility genes identified in other linkage studies.

    View details for Web of Science ID 000170108100015

    View details for PubMedID 11404817

    View details for PubMedCentralID PMC1226029

  • Histopathology of familial ovarian tumors in women from families with and without germline BRCA1 mutations HUMAN PATHOLOGY Werness, B. A., Ramus, S. J., Whittemore, A. S., Garlinghouse-Jones, K., Oakley-Girvan, I., DiCioccio, R. A., Tsukada, Y., Ponder, B. A., Piver, M. S. 2000; 31 (11): 1420-1424


    Breast cancers from patients with germline BRCA1 mutations show characteristic histopathologic features. However, similar studies of BRCA1-associated ovarian cancers have reported inconsistent findings. Interobserver differences in histopathologic classification are a significant source of variation, and most studies have obtained histopathologic information from pathology reports rather than from review of histopathology slides. We therefore reviewed the histopathology slides and pathology reports to determine histologic type, grade, and stage for cancers of the ovary or peritoneum in 217 women from 126 families enrolled in the Gilda Radner Familial Ovarian Cancer Registry. Peripheral blood DNA from at least 1 affected member of each family was analyzed for BRCA1 mutations, and tumors from BRCA1 mutation-positive families were compared with those from BRCA1-negative families. Of 66 patients from 36 BRCA1-positive families, 64 had ovarian carcinoma, 1 had an ovarian carcinoma in situ, and 1 had a dysgerminoma. Of 151 patients from 90 BRCA1-negative families, 135 had ovarian carcinoma, 10 had ovarian borderline tumors, 3 had ovarian sex cord/stromal tumors, and 3 had primary peritoneal carcinoma. There were fewer grade 1 (P <.001) and stage I (P =.10) cancers in patients from BRCA1-positive families than in patients from BRCA1-negative families. Neither mucinous nor borderline tumors were found in the BRCA1-positive families. Ovarian cancers arising in women from BRCA1-positive families are more likely to be high grade and nonmucinous than cancers arising in women from BRCA1-negative families. The absence of borderline tumors in patients from BRCA1-positive families adds to accumulating evidence that BRCA1 mutations do not play a role in the development of these tumors. HUM PATHOL 31:1420-1424.

    View details for DOI 10.1053/hupa.2000.20379

    View details for Web of Science ID 000165454200014

    View details for PubMedID 11112219

  • Primary ovarian dysgerminoma in a patient with a germline BRCA1 mutation INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY Werness, B. A., Ramus, S. J., Whittemore, A. S., Garlinghouse-Jones, K., Oakley-Girvan, I., DiCioccio, R. A., Tsukada, Y., Ponder, B. A., Piver, M. S. 2000; 19 (4): 390-394


    Germline mutations in the BRCA1 tumor suppressor gene are associated with increased risk for the development of ovarian cancer. All such cancers thus far reported have been of the epithelial histologic type. We identified an ovarian dysgerminoma in a 16-year-old woman (proband) with a family history of ovarian cancer during a review of histopathologic characteristics of ovarian cancers from women enrolled in the Gilda Radner Familial Ovarian Cancer Registry. Mutation analysis of DNA from this patient's peripheral blood leukocytes revealed a germline BRCA1 mutation (3312insG). The mutation was also present in the mother with breast cancer, a maternal aunt and a distant cousin with ovarian cancer, and a maternal grandfather and an uncle with skin cancer. The development of the proband's dysgerminoma may be unrelated to her germline BRCA1 mutation. Alternatively, such dysgerminomas may be caused by BRCA1 mutations, but occur so infrequently compared with epithelial cancers that they are seldom identified. Analysis of a larger series of ovarian germ cell tumors may resolve this question.

    View details for Web of Science ID 000165354100017

    View details for PubMedID 11109172

  • Survival in epithelial ovarian cancer patients with prior breast cancer AMERICAN JOURNAL OF EPIDEMIOLOGY McGuire, V., Whittemore, A. S., Norris, R., Oakley-Girvan, I. 2000; 152 (6): 528-532


    Ovarian cancer patients who carry germ-line BRCA1 mutations may have improved survival compared with ovarian cancer patients without these mutations. To evaluate this hypothesis, the authors compared survival in ovarian cancer patients who had a history of prior breast cancer with that of patients without such a history. Specifically, they used data from the population-based US Surveillance, Epidemiology, and End Results (SEER) Program to assess time to death from ovarian cancer among ovarian cancer patients with and without a prior breast cancer. All 25,637 White women diagnosed with invasive epithelial ovarian cancer in SEER registries between 1973 and 1995 were included. Of these, 824 women had had a prior breast cancer diagnosis. The ovarian cancer death rate among women with prior breast cancer was significantly lower than that of women with ovarian cancer only, adjusted for age and stage at ovarian cancer diagnosis. The survival advantage was most pronounced among older women and among those whose ovarian cancers were more advanced at the time of diagnosis. These results lend indirect support to prior findings of improved ovarian cancer survival in BRCA1 mutation carriers.

    View details for Web of Science ID 000089252100004

    View details for PubMedID 10997542

  • Ovarian carcinoma in situ with germline BRCA1 mutation and loss of heterozygosity at BRCA1 and TP53 JOURNAL OF THE NATIONAL CANCER INSTITUTE Werness, B. A., Parvatiyar, P., Ramus, S. J., Whittemore, A. S., Garlinghouse-Jones, K., Oakley-Girvan, I., DiCioccio, R. A., Wiest, J., Tsukada, Y., Ponder, B. A., Piver, M. S. 2000; 92 (13): 1088-1091


    The two-hit hypothesis for the genesis of cancer predicts that cancer can develop when the wild-type allele of a tumor suppressor gene is lost in an individual with a germline mutation in that gene. Neither loss of heterozygosity (LOH) for BRCA1 nor mutations of the TP53 (also known as p53) gene have been documented prior to invasion in ovarian cancers arising in women with germline BRCA1 mutations. Such documentation is difficult because lesions are rarely identified in ovarian epithelium. We, therefore, looked for LOH at microsatellite polymorphisms linked to the BRCA1 and TP53 tumor suppressor loci in an incidental carcinoma in situ of the ovary removed prophylactically from a woman with a germline BRCA1 mutation.By use of laser-capture microdissection, we obtained pure populations of atypical ovarian epithelial cells and normal stromal cells. DNA was extracted, amplified with primers flanking polymorphic microsatellites linked to BRCA1 (D17S855 and D17S579) and TP53 (TP53 and D17S786), and analyzed for LOH at these microsatellites. We also tested for p53 expression in the abnormal epithelium by immunohistochemistry.Both of the markers linked to TP53 showed LOH, as did an intragenic BRCA1-linked marker (D17S855). The other microsatellite marker for BRCA1 was uninformative. Immunohistochemical staining with an antibody to p53 showed strong immunoreactivity confined to the atypical epithelium.BRCA1, as well as TP53, can undergo LOH prior to stromal invasion in BRCA1-associated ovarian cancer. Strong immunoreactivity for p53 suggests the presence of mutated p53 in these cells as well. These findings suggest that loss of function of these two tumor suppressor genes occurs early in ovarian carcinogenesis in BRCA1 mutation carriers.

    View details for Web of Science ID 000087993000015

    View details for PubMedID 10880552

  • No evidence of linkage for chromosome 1q42.2-43 in prostate cancer AMERICAN JOURNAL OF HUMAN GENETICS Whittemore, A. S., Lin, I. G., Oakley-Girvan, I., Gallagher, R. P., Halpern, J., Kolonel, L. N., Wu, A. H., Hsieh, C. L. 1999; 65 (1): 254-256

    View details for Web of Science ID 000081224300033

    View details for PubMedID 10364541

  • Dietary fat, calories, and prostate cancer risk JOURNAL OF THE NATIONAL CANCER INSTITUTE Bosland, M. C., Oakley-Girvan, I., Whittemore, A. S. 1999; 91 (6): 489-491

    View details for Web of Science ID 000079235100001

    View details for PubMedID 10088612

  • Prostate cancer susceptibility locus on chromosome 1q: a confirmatory study JOURNAL OF THE NATIONAL CANCER INSTITUTE Hsieh, C. L., Oakley-Girvan, I., Gallagher, R. P., Wu, A. H., Kolonel, L. N., Teh, C. Z., Halpern, J., West, D. W., Paffenbarger, R. S., Whittemore, A. S. 1997; 89 (24): 1893-1894

    View details for Web of Science ID 000071024900016

    View details for PubMedID 9414179



    Increasing scientific and public interest in hereditary cancer syndromes has created a need for estimates of lifetime cancer risks among members of families with such syndromes.Data from the Gilda Radner Familial Ovarian Cancer Registry were used to evaluate risk for cancers of the breast, cervix, uterus, colorectum, and prostate in members of 143 families containing three or more reported cases of ovarian cancer among first- or second-degree relatives. These risks were compared with those that were expected based on general population rates obtained from the Connecticut Tumor Registry.Overall, family members' risk of cancer at any nonovarian site was 1.5 times that of the general population (P < 0.001). Among female members, risk for cancer of the breast was 2.5 times that of the general population. Risk for cancer of the uterus was 5 times that of the general population and increased with increasing number of first-degree relatives with ovarian cancer. Among male family members having three or more first-degree relatives with ovarian cancer, prostate cancer risk was 4.5 times that of the general population. No excess risks were observed for cancer of the colorectum.These data support previous reports of coaggregation of cancer of the breast, uterus and ovary, and suggest coaggregation between cancer of the ovary and prostate. Differences in cancer risk profiles observed in these families with multiple ovarian cancer and in carriers of the gene BRCA1 suggest that hereditary ovarian cancer is genetically heterogeneous.

    View details for Web of Science ID A1995RY50600017

    View details for PubMedID 8620417

  • Quantitative anatomical study of taste buds n fungiform papillae of young and old Fischer rats J Gerontol Mistretta CM, Oakley IA 1986; 41 (3): 315-318