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Genome-wide association study identifies five new susceptibility loci for prostate cancer in the Japanese population

Nature Genetics volume 42, pages 751–754 (2010)Cite this article

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Abstract

Prostate cancer is one of the most common malignancies in males throughout the world1, and its incidence is increasing in Asian countries. We carried out a genome-wide association study and replication study using 4,584 Japanese men with prostate cancer and 8,801 control subjects. From the thirty-one associated SNPs reported in previous genome-wide association studies in European populations, we confirmed the association of nine SNPs at P < 1.0 × 10−7 and ten SNPs at P < 0.05 in the Japanese population. The remaining 12 SNPs showed no association (P > 0.05). In addition, we report here five new loci for prostate cancer susceptibility, at 5p15 (λ-corrected probability PGC = 3.9 × 10−18), GPRC6A/RFX6 (PGC = 1.6 × 10−12), 13q22 (PGC = 2.8 × 10−9), C2orf43 (PGC = 7.5 × 10−8) and FOXP4 (PGC = 7.6 × 10−8). These findings advance our understanding of the genetic basis of prostate carcinogenesis and also highlight the genetic heterogeneity of prostate cancer susceptibility among different ethnic populations.

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Figure 1: Case-control association results and LD maps of the five new prostate cancer susceptibility loci.

References

  1. Parkin, D.M., Bray, F., Ferlay, J. & Pisani, P. Global cancer statistics, 2002. CA Cancer J. Clin. 55, 74–108 (2005).

    Article  Google Scholar 

  2. Matsuda, T. & Saika, K. Comparison of time trends in prostate cancer incidence (1973–2002) in Asia, from cancer incidence in five continents, Vols IV–IX. Jpn. J. Clin. Oncol. 39, 468–469 (2009).

    Article  Google Scholar 

  3. Kurahashi, N. et al. Dairy product, saturated fatty acid, and calcium intake and prostate cancer in a prospective cohort of Japanese men. Cancer Epidemiol. Biomarkers Prev. 17, 930–937 (2008).

    Article  CAS  Google Scholar 

  4. Schaid, D.J. The complex genetic epidemiology of prostate cancer. Hum. Mol. Genet. 13, R103–R121 (2004).

    Article  CAS  Google Scholar 

  5. Lichtenstein, P. et al. Environmental and heritable factors in the causation of cancer–analyses of cohorts of twins from Sweden, Denmark, and Finland. N. Engl. J. Med. 343, 78–85 (2000).

    Article  CAS  Google Scholar 

  6. Gudmundsson, J. et al. Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24. Nat. Genet. 39, 631–637 (2007).

    Article  CAS  Google Scholar 

  7. Yeager, M. et al. Genome-wide association study of prostate cancer identifies a second risk locus at 8q24. Nat. Genet. 39, 645–649 (2007).

    Article  CAS  Google Scholar 

  8. Gudmundsson, J. et al. Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes. Nat. Genet. 39, 977–983 (2007).

    Article  CAS  Google Scholar 

  9. Gudmundsson, J. et al. Common sequence variants on 2p15 and Xp11.22 confer susceptibility to prostate cancer. Nat. Genet. 40, 281–283 (2008).

    Article  CAS  Google Scholar 

  10. Eeles, R.A. et al. Multiple newly identified loci associated with prostate cancer susceptibility. Nat. Genet. 40, 316–321 (2008).

    Article  CAS  Google Scholar 

  11. Thomas, G. et al. Multiple loci identified in a genome-wide association study of prostate cancer. Nat. Genet. 40, 310–315 (2008).

    Article  CAS  Google Scholar 

  12. Gudmundsson, J. et al. Genome-wide association and replication studies identify four variants associated with prostate cancer susceptibility. Nat. Genet. 41, 1022–1026 (2009).

    Article  Google Scholar 

  13. Eeles, R.A. et al. Identification of seven new prostate cancer susceptibility loci through a genome-wide association study. Nat. Genet. 41, 1116–1121 (2009).

    Article  CAS  Google Scholar 

  14. Yeager, M. et al. Identification of a new prostate cancer susceptibility locus on chromosome 8q24. Nat. Genet. 41, 1055–1057 (2009).

    Article  CAS  Google Scholar 

  15. Al Olama, A.A. et al. Multiple loci on 8q24 associated with prostate cancer susceptibility. Nat. Genet. 41, 1058–1060 (2009).

    Article  CAS  Google Scholar 

  16. Witte, J.S. Prostate cancer genomics: towards a new understanding. Nat. Rev. Genet. 10, 77–82 (2009).

    Article  CAS  Google Scholar 

  17. Freedman, M.L. et al. Assessing the impact of population stratification on genetic association studies. Nat. Genet. 36, 388–393 (2004).

    Article  CAS  Google Scholar 

  18. Yamaguchi-Kabata, Y. et al. Japanese population structure, based on SNP genotypes from 7003 individuals compared to other ethnic groups: effects on population-based association studies. Am. J. Hum. Genet. 83, 445–456 (2008).

    Article  CAS  Google Scholar 

  19. Devlin, B. & Roeder, K. Genomic control for association studies. Biometrics 55, 997–1004 (1999).

    Article  CAS  Google Scholar 

  20. Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447, 661–678 (2007).

  21. Barrett, J., Fry, B., Maller, J. & Daly, M. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21, 263–265 (2005).

    Article  CAS  Google Scholar 

  22. Aftab, S., Semenec, L., Chu, J.S. & Chen, N. Identification and characterization of novel human tissue-specific RFX transcriptional factors. BMC Evol. Biol. 8, 226 (2008).

    Article  Google Scholar 

  23. Pi, M. et al. GPRC6A null mice exhibit osteopenia, feminization and metabolic syndrome. PLoS One 3, e3858 (2008).

    Article  Google Scholar 

  24. Teufel, A., Wong, E.A., Mukhopadhyay, M., Malik, N. & Westphal, H. FoxP4, a novel forkhead transcription factor. Biochim. Biophys. Acta 1627, 147–152 (2003).

    Article  CAS  Google Scholar 

  25. Croucher, P.J. et al. Haplotype structure and association to Crohn′s disease of CARD15 mutations in two ethnically divergent populations. Eur. J. Hum. Genet. 11, 6–16 (2003).

    Article  CAS  Google Scholar 

  26. Nakamura, Y. The BioBank Japan project. Clin. Adv. Hematol. Oncol. 5, 696–697 (2007).

    Google Scholar 

  27. Ohnishi, Y. et al. A high-throughput SNP typing system for genome-wide association studies. J. Hum. Genet. 46, 471–477 (2001).

    Article  CAS  Google Scholar 

  28. Gabriel, S.B. et al. The structure of haplotype blocks in the human genome. Science 296, 2225–2229 (2002).

    Article  CAS  Google Scholar 

  29. Purcell, S. et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. 81, 559–575 (2007).

    Article  CAS  Google Scholar 

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Acknowledgements

We thank K. Ashikawa, H. Amitani and other staff from the Laboratory for Genotyping Development, Center for Genomic Medicine, RIKEN for their contribution to SNP genotyping, K. Boroevich for comments on the manuscript, and 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, which was supported by the Ministry of Education, Culture, Sports, Sciences and Technology of the Japanese government.

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Authors and Affiliations

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

    Ryo Takata, Shusuke Akamatsu & Hidewaki Nakagawa

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

    Ryo Takata & Tomoaki Fujioka

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

    Shusuke Akamatsu & Osamu Ogawa

  4. Laboratory for Genotyping Development, Center of Genomic Medicine, RIKEN, Yokohama, Japan

    Michiaki Kubo & Naoya Hosono

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

    Atsushi Takahashi & Naoyuki Kamatani

  6. Laboratory for Medical Informatics, Center of Genomic Medicine, RIKEN, Yokohama, Japan

    Takahisa Kawaguchi & Tatsuhiko Tsunoda

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

    Johji Inazawa

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

    Yusuke Nakamura

Authors
  1. Ryo Takata
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Contributions

Y.N. conceived the study; Y.N., R.T., S.A., M.K. and H.N. designed the study; R.T., S.A., N.H. and M.K. performed genotyping; R.T., S.A., M.K., Y.N. and H.N. wrote the manuscript; A.T., T.K., T.T. and N.K. performed data analysis at the genome-wide phase; Y.N., H.N. and M.K. managed DNA samples; R.T. and H.N. summarized the results; Y.N., O.O., T.F. and J.I. 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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Supplementary Figures 1 and 2 and Supplementary Tables 1–6 (PDF 681 kb)

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Takata, R., Akamatsu, S., Kubo, M. et al. Genome-wide association study identifies five new susceptibility loci for prostate cancer in the Japanese population. Nat Genet 42, 751–754 (2010). https://doi.org/10.1038/ng.635

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