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Common variants at 11q12, 10q26 and 3p11.2 are associated with prostate cancer susceptibility in Japanese. Nat Genet 44(426-9):S1

Laboratory for Biomarker Development, Center for Genomic Medicine, RIKEN, Tokyo, Japan.
Nature Genetics (Impact Factor: 29.65). 02/2012; 44(4):426-9, S1. DOI: 10.1038/ng.1104
Source: PubMed

ABSTRACT We have previously reported multiple loci associated with prostate cancer susceptibility in a Japanese population using a genome-wide association study (GWAS). To identify additional prostate cancer susceptibility loci, we genotyped nine SNPs that were nominally associated with prostate cancer (P < 1 × 10(-4)) in our previous GWAS in three independent studies of prostate cancer in Japanese men (2,557 individuals with prostate cancer (cases) and 3,003 controls). In a meta-analysis of our previous GWAS and the replication studies, which included a total of 7,141 prostate cancer cases and 11,804 controls from a single ancestry group, three new loci reached genome-wide significance on chromosomes 11q12 (rs1938781; P = 1.10 × 10(-10); FAM111A-FAM111B), 10q26 (rs2252004; P = 1.98 × 10(-8)) and 3p11.2 (rs2055109; P = 3.94 × 10(-8)). We also found suggestive evidence of association at a previously reported prostate cancer susceptibility locus at 2p11 (rs2028898; P = 1.08 × 10(-7)). The identification of three new susceptibility loci should provide additional insight into the pathogenesis of prostate cancer and emphasizes the importance of conducting GWAS in diverse populations.

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    • "As of October 2012, a total of 94 single nucleotide polymorphisms (SNPs) across 41 chromosomal loci were reported to achieve a genome-wide significance level, which we conservatively define in this report as a p-value < 10-6 in order to maximize capture of potential loci, across 18 GWAS (Figure 1 and Additional file 1: Table S1). Of the 18 GWAS, a total of 15 (83%) were performed within a European (including one Latin American [15]) study population, two on a Japanese cohort [16,17] and a single GWAS has exclusively targeted African American’s [18]. "
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    • "A recent GWAS PCa study identified rs2252004 at 10q26 to be significantly associated with PCa risk at a genome-wide significant level (P = 1.98E − 8) in the Japanese population [11]. It was further confirmed to contribute to PCa risk in a Chinese population [12]. "
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    • "Today GWAS have been remarkably successful in identifying dozens of common genetic variants or loci associated with PCa [239] [240] [241]. Most of those PCa predisposition SNP loci were initially identified in Western populations and half of them are not associated with PCa risk in the East Asian population [239] [240]. Two SNPs located at chromosome 4 have also been reported to show specific ethnical association with PCa risk [242]: rs12500426, which exhibited an association in Europeans but not in Asian or African American men and rs7679673, which was associated with disease in European and Asian populations but not in African American men. "
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