Prostate cancer is one of the leading causes of morbidity and mortality among men. At the moment, we do not understand the underlying etiology, or why different groups, such as African Americans, have higher rates of disease. Risk factors for prostate cancer have remained elusive and aside from age, having a family history of the disease or African ancestry, until recently, no genetic or non-genetic (i.e., lifestyle) risk factors have been consistently demonstrated to contribute to variation in disease risk in the population. In this application, we propose to undertake a large-scale collaborative effort to uncover genetic predictors of prostate cancer in African American men. For this effort, we have assembled a multi-institutional team of investigators with experience in prostate cancer research in minority populations who are eager and willing to pool resources, specimens and data from their established studies, and to work closely together towards a common goal. To identify genetic factors that contribute to prostate cancer risk in African American men we propose to conduct a well-powered multi-stage genome-wide association study. In stage 1 we will genotype 1,000,000 single nucleotide polymorphisms (SNPs) in 1,500 African American prostate cancer cases and 1,500 controls. In stage 2 we will perform follow-up genotyping of 24,000 SNPs that demonstrate significant main effects and interactions with known risk variants for prostate cancer (e.g. 8q24) in an additional 1,626 African American cases and 1,867 controls. In stage 3, we will further examine genetic associations from stage 1+2 in an additional 1,124 African American cases and 1,163 controls. In this study we will also assess the pan-ethnic effects of the variants identify in the African American scan, by replication testing in 3,900 prostate cancer cases and 4,350 controls of West African, Japanese, Latino and European American ancestry. In this dataset, we will also examine interactions between associated variants, environmental factors (thereby better defining the role of these factors) and disease severity. We expect this work to significantly advance knowledge of the etiology of prostate cancer and racial/ethnic disparities in prostate cancer risk, and to guide the development of future preventive, early detection, prognostic and even therapeutic measures.

Public Health Relevance

The goal of this project is to identify common risk alleles for prostate cancer in African American men. For this effort, we have assembled a multi-institutional team of investigators with experience in prostate cancer research in minority populations who are eager and willing to pool resources, specimens and data from their established studies, and to work closely together towards a common goal. More specifically, we propose to conduct a multi-stage genome-wide association study of prostate cancer, which will include 4,250 African American cases and 4,530 African American male controls. We will examine the pan-ethnic effects of associated variants in other racial/ethnic populations as well as incorporate environment and lifestyle risk factors in association testing to assist in better defining the subgroups of the African American population at greatest risk of developing this common cancer. We expect findings from this work to guide the development of future preventive, early detection and prognostic strategies.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01CA136792-02
Application #
7793610
Study Section
Special Emphasis Panel (ZRG1-HOP-T (02))
Program Officer
Martin, Damali
Project Start
2009-03-25
Project End
2012-02-29
Budget Start
2010-03-01
Budget End
2011-02-28
Support Year
2
Fiscal Year
2010
Total Cost
$2,379,805
Indirect Cost
Name
University of Southern California
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Wang, Hansong; Schmit, Stephanie L; Haiman, Christopher A et al. (2017) Novel colon cancer susceptibility variants identified from a genome-wide association study in African Americans. Int J Cancer 140:2728-2733
Justice, Anne E (see original citation for additional authors) (2017) Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits. Nat Commun 8:14977
Yoneyama, S; Yao, J; Guo, X et al. (2017) Generalization and fine mapping of European ancestry-based central adiposity variants in African ancestry populations. Int J Obes (Lond) 41:324-331
Johnson, Eric O; Hancock, Dana B; Levy, Joshua L et al. (2016) KAT2B polymorphism identified for drug abuse in African Americans with regulatory links to drug abuse pathways in human prefrontal cortex. Addict Biol 21:1217-1232
Han, Ying; Signorello, Lisa B; Strom, Sara S et al. (2015) Generalizability of established prostate cancer risk variants in men of African ancestry. Int J Cancer 136:1210-7
Hancock, D B; Levy, J L; Gaddis, N C et al. (2015) Replication of ZNF804A gene variant associations with risk of heroin addiction. Genes Brain Behav 14:635-40
Hancock, Dana B; Levy, Joshua L; Gaddis, Nathan C et al. (2015) Cis-Expression Quantitative Trait Loci Mapping Reveals Replicable Associations with Heroin Addiction in OPRM1. Biol Psychiatry 78:474-84
YĆ¼ceba?, Sait Can; Ayd?n Son, Ye?im (2014) A prostate cancer model build by a novel SVM-ID3 hybrid feature selection method using both genotyping and phenotype data from dbGaP. PLoS One 9:e91404
Park, S Lani; Caberto, Christian P; Lin, Yi et al. (2014) Association of cancer susceptibility variants with risk of multiple primary cancers: The population architecture using genomics and epidemiology study. Cancer Epidemiol Biomarkers Prev 23:2568-78
Kocarnik, Jonathan M; Pendergrass, Sarah A; Carty, Cara L et al. (2014) Multiancestral analysis of inflammation-related genetic variants and C-reactive protein in the population architecture using genomics and epidemiology study. Circ Cardiovasc Genet 7:178-88

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