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

Nature Genetics volume 44, pages 426–429 (2012)Cite this article

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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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Authors and Affiliations

  1. Laboratory for Biomarker Development, Center for Genomic Medicine, RIKEN, Tokyo, Japan

    Shusuke Akamatsu, Ryo Takata & Hidewaki Nakagawa

  2. Department of Urology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Shusuke Akamatsu, Takahiro Inoue & Osamu Ogawa

  3. Department of Urology, Iwate Medical University, Morioka, Japan

    Ryo Takata & Tomoaki Fujioka

  4. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA

    Christopher A Haiman, Gary K Chen & Brian E Henderson

  5. Laboratory for Statistical Analysis, Center for Genomic Medicine, RIKEN, Yokohama, Japan

    Atsushi Takahashi & Naoyuki Kamatani

  6. Laboratory for Genotyping Development, Center for Genomic Medicine, RIKEN, Tokyo, Japan

    Michiaki Kubo

  7. Department of Pathology, Kochi Medical School, Nankoku, Japan

    Mutsuo Furihata

  8. Department of Molecular Cytogenetics, Medical Research Institute and School of Biomedical Science, Tokyo Medical and Dental University, Tokyo, Japan

    Johji Inazawa

  9. Epidemiology Program, Cancer Research Center, University of Hawaii, Honolulu, Hawaii, USA

    Loïc Le Marchand & Laurence N Kolonel

  10. Department of Public Health, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan

    Takahiko Katoh

  11. Department of Hygiene and Preventive Medicine, Showa University School of Medicine, Tokyo, Japan

    Yuko Yamano

  12. Center for Multiphasic Health Testing and Services, Mitsui Memorial Hospital, Tokyo, Japan

    Minoru Yamakado

  13. Department of Pathology, The Jikei University School of Medicine, Tokyo, Japan

    Hiroyuki Takahashi

  14. Department of Urology, The Jikei University School of Medicine, Tokyo, Japan

    Hiroki Yamada & Shin Egawa

  15. Department of Urology, Akita University School of Medicine, Akita, Japan

    Tomonori Habuchi

  16. Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan

    Yusuke Nakamura

Authors
  1. Shusuke Akamatsu
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Contributions

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.

Corresponding author

Correspondence to Hidewaki Nakagawa.

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The authors declare no competing financial interests.

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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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