Journal
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
Volume 21, Issue 11, Pages 2048-2058Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1055-9965.EPI-12-0598
Keywords
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Funding
- NIH/National Human Genome Research Institute [U01 HG004726-01]
- Ministry of Education, Culture, Sports, Sciences and Technology of the Japanese government [22390306]
- Japan Society for the Promotion of Science
- Princess Takamatsu Cancer Research Fund
- Cancer Research UK [C5047/A7357, C1287/A10118, C5047/A3354, C5047/A10692, C16913/A6135, C16913/A6835, C522/A8649]
- NIH [U19 CA 148537-01]
- Institute of Cancer Research and The Everyman Campaign
- Prostate Cancer Research Foundation
- Prostate Action
- National Cancer Research Network UK
- National Cancer Research Institute (NCRI) UK
- NIHR
- Royal Marsden NHS Foundation Trust
- NIHR Health Technology Assessment Program [96/20/06, 96/20/99]
- Department of Health, England
- Medical Research Council of England [G0500966, 75466]
- USA Department of Defense award [W81XWH-04-1-0280]
- Yorkshire Cancer Research
- NCRI (ProMPT) Prostate Cancer Collaborative
- Cambridge BMRC grant from NIHR
- [U01 HG004446]
- Cancer Research UK [11022, 10118] Funding Source: researchfish
- Medical Research Council [G0500966] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0509-10242] Funding Source: researchfish
- Grants-in-Aid for Scientific Research [22390306] Funding Source: KAKEN
- MRC [G0500966] Funding Source: UKRI
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Background: There have been few genome-wide association studies (GWAS) of prostate cancer among diverse populations. To search for novel prostate cancer risk variants, we conducted GWAS of prostate cancer in Japanese and Latinos. In addition, we tested prostate cancer risk variants and developed genetic risk models of prostate cancer for Japanese and Latinos. Methods: Our first-stage GWAS of prostate cancer included Japanese (cases/controls = 1,033/1,042) and Latino (cases/controls = 1,043/1,057) from the Multiethnic Cohort (MEC). Significant associations from stage I (P < 1.0 x 10(-4)) were examined in silico in GWAS of prostate cancer (stage II) in Japanese (cases/controls = 1,583/3,386) and Europeans (cases/controls = 1,854/1,894). Results: No novel stage I single-nucleotide polymorphism (SNP) outside of known risk regions reached genome-wide significance. For Japanese, in stage I, the most notable putative novel association was seen with 10 SNPs (P < 8.0 x 10(-6)) at chromosome 203; however, this was not replicated in stage II. For Latinos, the most significant association was observed with rs17023900 at the known 3p12 risk locus (stage 1: OR = 1.45; P = 7.01 x 10(-5) and stage II: OR = 1.58; P = 3.05 x 10(-7)). The majority of the established risk variants for prostate cancer, 79% and 88%, were positively associated with prostate cancer in Japanese and Latinos (stage l), respectively. The cumulative effects of these variants significantly influence prostate cancer risk (OR per allele = 1.10; P = 2.71 x 10(-25) and OR = 1.07; P = 1.02 x 10(-16) for Japanese and Latinos, respectively). Conclusion and Impact: Our GWAS of prostate cancer did not identify novel genome-wide significant variants. However, our findings show that established risk variants for prostate cancer significantly contribute to risk among Japanese and Latinos. Cancer Epidemiol Biomarkers Prev; 21(11); 2048-58. (C)2012 AACR.
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