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Genome-wide association study in Chinese men identifies two new prostate cancer risk loci at 9q31.2 and 19q13.4


Prostate cancer risk–associated variants have been reported in populations of European descent, African-Americans and Japanese using genome-wide association studies (GWAS). To systematically investigate prostate cancer risk–associated variants in Chinese men, we performed the first GWAS in Han Chinese. In addition to confirming several associations reported in other ancestry groups, this study identified two new risk-associated loci for prostate cancer on chromosomes 9q31.2 (rs817826, P = 5.45 × 10−14) and 19q13.4 (rs103294, P = 5.34 × 10−16) in 4,484 prostate cancer cases and 8,934 controls. The rs103294 marker at 19q13.4 is in strong linkage equilibrium with a 6.7-kb germline deletion that removes the first six of seven exons in LILRA3, a gene regulating inflammatory response, and was significantly associated with the mRNA expression of LILRA3 in T cells (P < 1 × 10−4). These findings may advance the understanding of genetic susceptibility to prostate cancer.

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Figure 1: Regional association plots.
Figure 2: Germline deletion at LILRA3 and genotyped SNPs flanking the gene.


  1. Jemal, A. et al. Global cancer statistics. CA Cancer J. Clin. 61, 69–90 (2011).

    Google Scholar 

  2. Amundadottir, L.T. et al. A common variant associated with prostate cancer in European and African populations. Nat. Genet. 38, 652–658 (2006).

    CAS  Article  Google Scholar 

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

    CAS  Article  Google Scholar 

  4. 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).

    CAS  Article  Google Scholar 

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

    CAS  Article  Google Scholar 

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

    CAS  Article  Google Scholar 

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

    CAS  Article  Google Scholar 

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

    CAS  Article  Google Scholar 

  9. 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).

    CAS  Article  Google Scholar 

  10. Gudmundsson, J. et al. Genome-wide association and replication studies identify four variants associated with prostate cancer susceptibility. Nat. Genet. 41, 1122–1126 (2009).

    CAS  Article  Google Scholar 

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

    CAS  Article  Google Scholar 

  12. Kote-Jarai, Z. et al. Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study. Nat. Genet. 43, 785–791 (2011).

    CAS  Article  Google Scholar 

  13. Takata, R. et al. Genome-wide association study identifies five new susceptibility loci for prostate cancer in the Japanese population. Nat. Genet. 42, 751–754 (2010).

    CAS  Article  Google Scholar 

  14. Akamatsu, S. et al. Common variants at 11q12, 10q26 and 3p11.2 are associated with prostate cancer susceptibility in Japanese. Nat. Genet. 44, 426–429 (2012).

    CAS  Article  Google Scholar 

  15. Haiman, C.A. et al. Genome-wide association study of prostate cancer in men of African ancestry identifies a susceptibility locus at 17q21. Nat. Genet. 43, 570–573 (2011).

    CAS  Article  Google Scholar 

  16. Patterson, N., Price, A.L. & Reich, D. Population structure and eigen analysis. PLoS Genet. 2, e190 (2006).

    Article  Google Scholar 

  17. 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).

    CAS  Article  Google Scholar 

  18. Zheng, W. et al. Genome-wide association study identifies a new breast cancer susceptibility locus at 6q25.1. Nat. Genet. 41, 324–328 (2009).

    CAS  Article  Google Scholar 

  19. Zhang, X.J. et al. Psoriasis genome-wide association study identifies susceptibility variants within LCE gene cluster at 1q21. Nat. Genet. 41, 205–210 (2009).

    CAS  Article  Google Scholar 

  20. Yang, T.P. et al. Genevar: a database and Java application for the analysis and visualization of SNP-gene associations in eQTL studies. Bioinformatics 26, 2474–2476 (2010).

    CAS  Article  Google Scholar 

  21. Dimas, A.S. et al. Common regulatory variation impacts gene expression in a cell type–dependent manner. Science 325, 1246–1250 (2009).

    CAS  Article  Google Scholar 

  22. Nica, A.C. et al. The architecture of gene regulatory variation across multiple human tissues: the MuTHER study. PLoS Genet. 7, e1002003 (2011).

    CAS  Article  Google Scholar 

  23. Torkar, M. et al. Arrangement of the ILT gene cluster: a common null allele of the ILT6 gene results from a 6.7-kbp deletion. Eur. J. Immunol. 30, 3655–3662 (2000).

    CAS  Article  Google Scholar 

  24. Hirayasu, K. et al. Evidence for natural selection on leukocyte immunoglobulin-like receptors for HLA class I in Northeast Asians. Am. J. Hum. Genet. 82, 1075–1083 (2008).

    CAS  Article  Google Scholar 

  25. Borges, L., Hsu, M.L., Fanger, N., Kubin, M. & Cosman, D. A family of human lymphoid and myeloid Ig-like receptors, some of which bind to MHC class I molecules. J. Immunol. 159, 5192–5196 (1997).

    CAS  PubMed  Google Scholar 

  26. De Marzo, A.M. et al. Inflammation in prostate carcinogenesis. Nat. Rev. Cancer 7, 256–269 (2007).

    CAS  Article  Google Scholar 

  27. Liu, F. et al. Systematic confirmation study of reported prostate cancer risk–associated single nucleotide polymorphisms in Chinese men. Cancer Sci. 102, 1916–1920 (2011).

    CAS  Article  Google Scholar 

  28. Wang, M. et al. Replication and cumulative effects of GWAS-identified genetic variations for prostate cancer in Asians: a case-control study in the ChinaPCa consortium. Carcinogenesis 33, 356–360 (2012).

    Article  Google Scholar 

  29. Zheng, S.L. et al. Cumulative association of five genetic variants with prostate cancer. N. Engl. J. Med. 358, 910–919 (2008).

    CAS  Article  Google Scholar 

  30. Hirayasu, K. et al. Long-term persistence of both functional and non-functional alleles at the leukocyte immunoglobulin-like receptor A3 (LILRA3) locus suggests balancing selection. Hum. Genet. 119, 436–443 (2006).

    CAS  Article  Google Scholar 

  31. Pruim, R.J. et al. LocusZoom: regional visualization of genome-wide association scan results. Bioinformatics 26, 2336–2337 (2010).

    CAS  Article  Google Scholar 

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We thank all of the subjects included in this study. This work was partially funded by the National Key Basic Research Program grant 973 (2012CB518300 to Y.S and 2012CB518301 to J.X.), the Key Project of the National Natural Science Foundation of China (81130047 to J.X.), intramural grants from the Fudan University Thousand Talents Program and Huashan Hospital (to J.X.), the US National Institutes of Health (NCI CA129684 to J.X.), the National Natural Science Foundation of China (30945204 to Z.M and 30973009 to D.Y.), the Ministry of Health Special Research Fund for Public Interests (201002007 to L.J.) and the National Science & Technology Pillar Program (2011BAI09B00 to L.J.).

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Authors and Affiliations



Y.S., J.X. and Z.M. directed the study, obtained financial support and were responsible for study design, interpretation of results and manuscript writing. D.Y., M.W., F.L. and C.X. recruited study subjects and managed respective project. G.J. performed statistical analyses, summarized results and drafted the manuscript. X.W., Q.S., Z.C., Z.T., J.Q., F.Z., Zhong Wang (affiliation 20), Y.F., D.H., Q. Wei, J. Guo, D.W., Xin Gao, J. Yuan, Gongxian Wang, Y. Xu, Guozeng Wang, H. Yao, P.D., Y.J., M.S., J. Yang, J.O.-Y., H.J., Y. Zhu, S.R., Z.Z., C.Y., Xu Gao, B.D., Z.H., Y.Y., Q. Wu, H.C., P.P., Y. Zheng, X. Zheng, Y. Xiang, J. Gong, R.N. and X.L. recruited subjects and prepared samples. J.L., X.-O.S., W.Z. and X. Zhang provided the allele frequency data from their GWAS populations. H. Yu, Zhong Wang (affiliation 4), S.T., J.F., Jishan Sun and W.L. performed statistical and bioinformatics analyses and carried out experiments. F.W. and H.G. provided samples and information from CAPS. A.H., J.R., Q.D., H.S., L.J., R.S., D.L., Jielin Sun and S.L.Z. coordinated the project. All of the authors reviewed, approved and contributed to the final version of the manuscript.

Corresponding author

Correspondence to Yinghao Sun.

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The authors declare no competing financial interests.

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Supplementary Tables 1–11 and Supplementary Figures 1–7 (PDF 598 kb)

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Xu, J., Mo, Z., Ye, D. et al. Genome-wide association study in Chinese men identifies two new prostate cancer risk loci at 9q31.2 and 19q13.4. Nat Genet 44, 1231–1235 (2012).

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