Common variants at 11q12, 10q26 and 3p11.2 are associated with prostate cancer susceptibility in Japanese

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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Figure 1: Forest plots for association analysis of the 11q12, 10q26 and 3p11.2 regions.
Figure 2: Regional association plots.

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Acknowledgements

We thank the staff of the Laboratory for Genotyping Development at the Center for Genomic Medicine at RIKEN for their contribution to SNP genotyping, and K. Nakano and K. Watanabe for their technical assistance. We also thank Y. Mitobe and M. Kishida for sample management and clinical data collection. We are grateful to the members of the BioBank Japan Project and the Rotary Club of Osaka-Midosuji District 2660 Rotary International in Japan for supporting our study. This work was conducted as a part of the BioBank Japan Project that was supported by the Ministry of Education, Culture, Sports, Sciences and Technology of the Japanese government and was supported in part by a research grant from the Japan Society for the Promotion of Science (22390306 to H.N.), by the Princess Takamatsu Cancer Research Fund and by the Takeda Science Foundation. The Multiethnic Cohort (MEC) was supported by grants from the US National Institutes of Health (NIH; HG004726, CA148537, CA54281 and CA63464). S.A. is a Japan Society for the Promotion of Science Research Fellow.

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S.A., R.T., T.I., Y.N. and H.N. designed the study. S.A., R.T., C.A.H., M.K., G.K.C., L.L.M., L.N.K., T.K., Y.Y., M.Y., H.T., H.Y., S.E., T.F., B.E.H., T.H., O.O., Y.N. and H.N. contributed to sample collection, genotyping and data management. A.T. and N.K. contributed to the statistical analysis. S.A., C.A.H. and H.N. wrote the manuscript. M.F. performed immunohistochemistry, and S.A. performed functional experiments. S.A. and H.N. summarized the results. Y.N., O.O., T.F., J.I. and H.N. obtained funding for the study.

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Correspondence to Hidewaki Nakagawa.

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The authors declare no competing financial interests.

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Supplementary Figures 1–10 and Supplementary Tables 1–4 (PDF 1367 kb)

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Akamatsu, S., Takata, R., Haiman, C. et al. Common variants at 11q12, 10q26 and 3p11.2 are associated with prostate cancer susceptibility in Japanese. Nat Genet 44, 426–429 (2012). https://doi.org/10.1038/ng.1104

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