Prostate cancer is a leading cause of morbidity and mortality among men. 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. Over the past year, we contributed to the first reproducible genetic risk factor for prostate cancer at 8q24. Through fine-mapping of 8q24 in five racial/ethnic populations in the Multiethnic Cohort Study (MEC), we identified three regions that contain 7 independent risk variants for prostate cancer. Only some of these variants were found in studies conducted in European Whites, thus, emphasizing the power of genetic studies in multiple racial/ethnic populations to reveal a more complete spectrum of variants associated with disease risk. In this application, we propose to work with the GEI-GWA Steering Committee to identify genetic factors that contribute to prostate cancer by performing a well-powered genome-wide association study among African American, Japanese American, Native Hawaiian, Latino and European American men in the MEC. More specifically, we propose the genotyping of approximately 1,000,000 single nucleotide polymorphisms (SNPs) and >940,000 probes to detect copy number variation in 3,750 prostate cancer cases and 3,750 controls, to identify pan-ethnic genetic variants that affect risk in all five racial/ethnic populations, as well as important ethnic-specific variation. In this multi-ethnic dataset, we will also examine interaction between associated variants, environmental factors (thereby better defining the role of these factors) and disease severity, as well as explore the causes of heterogeneity of genetic effects across populations. We have also established collaborations with other prostate cancer researches to replicate the ethnic-specific associations observed in this GWA study in minority populations. We expect this work to significantly advance knowledge of the etiology of prostate cancer across these racial/ethnic populations, guiding the development of future preventive, early detection, prognostic and even therapeutic measures. ? ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Research Project--Cooperative Agreements (U01)
Project #
1U01HG004726-01
Application #
7514765
Study Section
Special Emphasis Panel (ZHG1-HGR-P (M1))
Program Officer
Wise, Anastasia Leigh
Project Start
2008-09-20
Project End
2010-06-30
Budget Start
2008-09-20
Budget End
2009-06-30
Support Year
1
Fiscal Year
2008
Total Cost
$198,480
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
Silvestrov, Pavel; Maier, Sarah J; Fang, Michelle et al. (2018) DNArCdb: A database of cancer biomarkers in DNA repair genes that includes variants related to multiple cancer phenotypes. DNA Repair (Amst) 70:10-17
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
Walker, Alice R; Silvestrov, Pavel; Müller, Tina A et al. (2017) ALKBH7 Variant Related to Prostate Cancer Exhibits Altered Substrate Binding. PLoS Comput Biol 13:e1005345
Schmit, Stephanie L; Schumacher, Fredrick R; Edlund, Christopher K et al. (2016) Genome-wide association study of colorectal cancer in Hispanics. Carcinogenesis 37:547-556
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; Rand, Kristin A; Hazelett, Dennis J et al. (2016) Prostate Cancer Susceptibility in Men of African Ancestry at 8q24. J Natl Cancer Inst 108:
Rand, Kristin A; Rohland, Nadin; Tandon, Arti et al. (2016) Whole-exome sequencing of over 4100 men of African ancestry and prostate cancer risk. Hum Mol Genet 25:371-81
Machiela, Mitchell J; Zhou, Weiyin; Karlins, Eric et al. (2016) Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome. Nat Commun 7:11843
Newcombe, Paul J; Conti, David V; Richardson, Sylvia (2016) JAM: A Scalable Bayesian Framework for Joint Analysis of Marginal SNP Effects. Genet Epidemiol 40:188-201
Rand, Kristin A; Song, Chi; Dean, Eric et al. (2016) A Meta-analysis of Multiple Myeloma Risk Regions in African and European Ancestry Populations Identifies Putatively Functional Loci. Cancer Epidemiol Biomarkers Prev 25:1609-1618

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