This project includes analytic and methodologic studies aimed at assessing the epidemiology of prostate cancer and clarifying, through biochemical and methodologic studies, the biological underpinnings of how lifestyle factors influence the risk of prostate cancer. Our efforts relate to a variety of environmental, genetic, and hormonal predictors of prostate cancer risk in special populations. We have conducted a multidisciplinary study in China to assess risk factors for prostate cancer in a low-risk population in order to understand more clearly the reasons for the large racial differences in prostate cancer risk. That study involved the collection of multiple biologic samples, with a primary aim of assessing risk factors and how westernization influences the risk of prostate cancer. The study also involved the collection of tissue samples from prostate cancer tumors to permit precise tumor classification as well as assays of tumor biomarkers, in some cases using newly developed tissue micro array techniques. In addition to specific dietary factors, dietary patterns will be identified and compared with those of controls to evaluate whether a western-style diet in China is related to excess prostate cancer risk. The study is also assessing biological correlates of westernization to look for potential biological links between westernization and excess prostate cancer risk. Data on genotypes and circulating levels of hormones provide a unique opportunity to investigate the interrelationships between serum hormones and genetic variants to gain insights into the functional significance of these genetic markers. In another study of prostate cancer in 15 cities in China, we are assessing the role of soy in prostate cancer by developing a dietary isoflavone index. A population-based survey is currently underway in Ghana, Africa, to assess the burden of prostate cancer in African men. This study will collect clinical/pathological data from over 500 men diagnosed with prostate cancer during the last 5 years and screen 1,038 healthy men for prostate cancer by digital rectal examination and prostate specific antigen to evaluate the burden of prostate cancer in West African men. Biological samples collected from these 1,038 healthy men will provide a unique resource to establish the nutritional, hormonal, and genetic profiles of African men. In addition, linking interview data from these 1, 038 healthy subjects with biomarkers from them will produce insights into whether westernization in African men is associated with an adverse metabolic profile (obesity;abdominal obesity;higher levels of insulin, low-density lipoprotein, and insulin-like growth factor I), which has been associated with excess prostate cancer risk. We further expand case recruitment to include an additional 500 cancer cases for a genome wide association study (GWAS). We have recently sequenced the 8q24 region and identified several novel variants in this region. In several nested case-control studies in large cohorts, including Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, and the Prostate Cancer Prevention Trial (PCPT), and the American Cancer Society Nutrition Cohort (CPS-II), we are assessing the relationships of obesity, dietary patterns, insulin resistance, and chronic inflammation with subsequent risk of prostate cancer in three prospective studies, including the Together, these cohorts provide over 3,000 prostate cancer cases for the investigation of prostate cancer etiology. They are unique in having collected pre-morbid blood and multiple biologic samples over time, permitting an assessment of how hormone and other biomarker levels change as patients approach diagnosis. A methodologic study is currently underway to evaluate whether circulating levels of androgens reflect intraprostatic androgenicity, a key issue in hormonal carcinogenesis of the prostate. This methodologic study will collect samples of fasting blood and snap-frozen fresh tissue (over 3,000 pieces) from 600 study subjects in three racial/ethnic groups. Data from this study will provide a unique opportunity to investigate the interrelationships among serum and tissue hormones and variants in genes involved in the androgen metabolism pathways to provide critical data for determining the functional significance of these genetic markers. The collection of tissue samples also will provide a unique opportunity for gene expression studies.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIACP010180-10
Application #
8349579
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
2011
Total Cost
$450,185
Indirect Cost
Name
Division of Cancer Epidemiology and Genetics
Department
Type
DUNS #
City
State
Country
Zip Code
Cook, Michael B; Stanczyk, Frank Z; Wood, Shannon N et al. (2017) Relationships between Circulating and Intraprostatic Sex Steroid Hormone Concentrations. Cancer Epidemiol Biomarkers Prev 26:1660-1666
Zhou, Cindy Ke; Stanczyk, Frank Z; Hafi, Muhannad et al. (2017) Circulating and intraprostatic sex steroid hormonal profiles in relation to male pattern baldness and chest hair density among men diagnosed with localized prostate cancers. Prostate 77:1573-1582
Ke Zhou, Cindy; Young, Denise; Yeboah, Edward D et al. (2017) TMPRSS2-ERG Gene Fusions in Prostate Cancer of West African Men and a Meta-analysis of Racial Differences. Am J Epidemiol :
Yeboah, E D; Hsing, A W; Mante, S et al. (2016) MANAGEMENT OF PROSTATE CANCER IN ACCRA, GHANA. J West Afr Coll Surg 6:31-65
Cook, Michael Blaise; Wang, Zhaoming; Yeboah, Edward D et al. (2014) A genome-wide association study of prostate cancer in West African men. Hum Genet 133:509-21
Sklavos, Martha M; Zhou, Cindy Ke; Pinto, Ligia A et al. (2014) Prediagnostic circulating anti-Müllerian hormone concentrations are not associated with prostate cancer risk. Cancer Epidemiol Biomarkers Prev 23:2597-602
Hsing, Ann W; Yeboah, Edward; Biritwum, Richard et al. (2014) High prevalence of screen detected prostate cancer in West Africans: implications for racial disparity of prostate cancer. J Urol 192:730-5
Al Olama, Ali Amin; Kote-Jarai, Zsofia; Berndt, Sonja I et al. (2014) A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer. Nat Genet 46:1103-9
Buadi, Francis; Hsing, Ann W; Katzmann, Jerry A et al. (2011) High prevalence of polyclonal hypergamma-globulinemia in adult males in Ghana, Africa. Am J Hematol 86:554-8
Kosti, O; Goldman, L; Saha, D T et al. (2011) DNA damage phenotype and prostate cancer risk. Mutat Res 719:41-6

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