Prostate cancer is the most commonly occurring cancer in U.S. men. African American men have the highest prostate cancer rate in the world. There is relatively little information available about the etiologic factors that may explain these rates. The objective of the present study is to examine the role of genes that regulate the disposition of testosterone in prostate cancer etiology, and to evaluate whether these genes explain, in part, differences in prostate cancer rates between African Americans and U.S. Caucasians. These genes include the cytochromes P450 CYP3A4 and CYP19, 5alpha-reductase II (SRD5A2), androgen receptor (AR), and the type II 3beta-hydroxy-steroid dehydrogenase (HSD3beta2). All of these genes are involved in the downstream metabolism of testosterone, and thus focus our hypotheses on a relevant, defined set of metabolic pathways.
Three specific aims are proposed here.
In Specific Aim 1, we will systematically evaluate allelic and genotypic distributions at these candidate genes, and compare these distributions in four ethnic groups (Ghanaian, Senegalese, African American, and US Caucasian men). In addition, obtaining data from Ghana and Senegal will initiate collaborations to foster formal studies of prostate cancer etiology in Africans.
In Specific Aim 2, we propose to undertake both case-case and case-control analyses to evaluate the relationship of candidate genotypes with prostate cancer in African Americans.
In Specific Aim 3, we propose to evaluate differences in the genotype-prostate cancer relationship between African Americans and Caucasians. We will again use case-case and case-control designs to evaluate differences in prostate cancer etiology between these two groups. In order to address these hypotheses, we will undertake a study using an existing subject accrual system to identify a sample of 800 incident prostate cancer cases and 800 controls. Half of these will be African American and half will be Caucasian. A sample of healthy Ghanaian and Senegalese controls will also be accrued. Risk factor information will be obtained from a questionnaire interview, a biosample containing DNA will be collected using a non-invasive cheek swab method, and pathology information will be collected using a standardized medical record abstraction approach. An understanding of the complex interplay of genetic variability at multiple loci and of environmental agents may improve our understanding of prostate cancer etiology and risk prediction. This information could then be used to more effectively apply prostate cancer prevention and control strategies.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1 (01))
Program Officer
Rosenfeld, Bobby
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Pennsylvania
Biostatistics & Other Math Sci
Schools of Medicine
United States
Zip Code
Lynch, Shannon M; Mitra, Nandita; Ravichandran, Krithika et al. (2017) Telomere Length and Neighborhood Circumstances: Evaluating Biological Response to Unfavorable Exposures. Cancer Epidemiol Biomarkers Prev 26:553-560
Lynch, Shannon M; Peek, M K; Mitra, Nandita et al. (2016) Race, Ethnicity, Psychosocial Factors, and Telomere Length in a Multicenter Setting. PLoS One 11:e0146723
Yamoah, Kosj; Zeigler-Johnson, Charnita M; Jeffers, Abra et al. (2016) The impact of body mass index on treatment outcomes for patients with low-intermediate risk prostate cancer. BMC Cancer 16:557
Yamoah, Kosj; Deville, Curtiland; Vapiwala, Neha et al. (2015) African American men with low-grade prostate cancer have increased disease recurrence after prostatectomy compared with Caucasian men. Urol Oncol 33:70.e15-22
Yamoah, Kosj; Walker, Amy; Spangler, Elaine et al. (2015) African-american race is a predictor of seminal vesicle invasion after radical prostatectomy. Clin Genitourin Cancer 13:e65-72
Rebbeck, Timothy R; Haas, Gabriel P (2014) Temporal trends and racial disparities in global prostate cancer prevalence. Can J Urol 21:7496-506
Lynch, Shannon M; Rebbeck, Timothy R (2013) Bridging the gap between biologic, individual, and macroenvironmental factors in cancer: a multilevel approach. Cancer Epidemiol Biomarkers Prev 22:485-95
Rebbeck, Timothy R; Weber, Anita L; Spangler, Elaine et al. (2013) What stresses men? Predictors of perceived stress in a population-based multi-ethnic cross sectional cohort. BMC Public Health 13:113
Zeigler-Johnson, Charnita; Morales, Knashawn H; Spangler, Elaine et al. (2013) Relationship of early-onset baldness to prostate cancer in African-American men. Cancer Epidemiol Biomarkers Prev 22:589-96
Zhao, Huaqing; Rebbeck, Timothy R; Mitra, Nandita (2012) Analyzing genetic association studies with an extended propensity score approach. Stat Appl Genet Mol Biol 11:

Showing the most recent 10 out of 36 publications