Abstract

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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Acknowledgements

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.).

Author information

Author notes

    • Jianfeng Xu
    • , Zengnan Mo
    • , Dingwei Ye
    • , Meilin Wang
    • , Fang Liu
    • , Guangfu Jin
    •  & Chuanliang Xu

    These authors contributed equally to this work.

Affiliations

  1. Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai, China.

    • Jianfeng Xu
    • , Fang Liu
    • , Xiang Wang
    • , Haowen Jiang
    • , Jian Gong
    • , Rong Na
    • , Xiaoling Lin
    •  & Qiang Ding
  2. Fudan Center for Genetic Epidemiology, School of Life Sciences, Fudan University, Shanghai, China.

    • Jianfeng Xu
    • , Fang Liu
    • , Hongyan Chen
    • , Xiaoling Lin
    • , Hongjie Yu
    • , Daru Lu
    • , Jielin Sun
    •  & S Lilly Zheng
  3. State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.

    • Jianfeng Xu
    • , Hongyan Chen
    • , Hongjie Yu
    •  & Daru Lu
  4. Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.

    • Jianfeng Xu
    • , Guangfu Jin
    • , Zhong Wang
    • , Sha Tao
    • , Junjie Feng
    • , Jishan Sun
    • , Wennuan Liu
    • , Jielin Sun
    •  & S Lilly Zheng
  5. Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, China.

    • Zengnan Mo
  6. Department of Urology and Nephrology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.

    • Zengnan Mo
  7. Department of Urology, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China.

    • Dingwei Ye
    • , Yao Zhu
    •  & Bo Dai
  8. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.

    • Dingwei Ye
    • , Yao Zhu
    •  & Bo Dai
  9. Department of Molecular and Genetic Toxicology, The Key Laboratory of Modern Toxicology of the Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.

    • Meilin Wang
    •  & Zhengdong Zhang
  10. State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.

    • Meilin Wang
    • , Guangfu Jin
    • , Zhengdong Zhang
    • , Zhibin Hu
    •  & Hongbing Shen
  11. Department of Epidemiology and Biostatistics and Ministry of Education Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.

    • Guangfu Jin
    • , Zhibin Hu
    •  & Hongbing Shen
  12. Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China.

    • Guangfu Jin
    • , Zhibin Hu
    •  & Hongbing Shen
  13. Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China.

    • Chuanliang Xu
    • , Shancheng Ren
    • , Xu Gao
    •  & Yinghao Sun
  14. Department of Urology, Suzhou Municipal Hospital, Suzhou, China.

    • Qiang Shao
  15. Urology Institute of the People's Liberation Army (PLA), Southwest Hospital, Third Military Medical University, Chongqing, China.

    • Zhiwen Chen
  16. Department of Laboratory Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

    • Zhihua Tao
  17. Department of Urology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

    • Jun Qi
    •  & Yang Jiao
  18. State Key Laboratory of Oncology in Southern China, Guangzhou, China.

    • Fangjian Zhou
    •  & Pei Dong
  19. Department of Urology, Cancer Center, Sun Yat-Sen University, Guangzhou, China.

    • Fangjian Zhou
    •  & Pei Dong
  20. Department of Urology, Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

    • Zhong Wang
    •  & Haijun Yao
  21. Department of Urology, The First Hospital of Jilin University, Changchun, China.

    • Yaowen Fu
  22. Department of Urology, The First Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Xi'an, China.

    • Dalin He
  23. Department of Urology, West China Hospital, Sichuan University, Chengdu, China.

    • Qiang Wei
  24. Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.

    • Jianming Guo
  25. Department of Urology, Tongji Hospital, Tongji University, Shanghai, China.

    • Denglong Wu
  26. Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

    • Xin Gao
  27. Department of Urology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.

    • Jianlin Yuan
  28. Department of Urology, The First Affiliated Hospital of Nanchang University, Jiangxi, China.

    • Gongxian Wang
  29. Department of Urology, Second Hospital of TianJin Medical University, TianJin Institute of Urology, Tianjin, China.

    • Yong Xu
  30. Department of Urology, Pudong Gongli Hospital, Shanghai, China.

    • Guozeng Wang
  31. Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, China.

    • Mo Shen
  32. Department of Cell Biology, Third Military Medical University, Chongqing, China.

    • Jin Yang
  33. Department of Urology, First People's Hospital, Suzhou University, Suzhou, China.

    • Jun Ou-Yang
  34. Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

    • Changjun Yin
  35. Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.

    • Yajun Yang
    • , Li Jin
    •  & Daru Lu
  36. Fudan-Taizhou Institute of Health Sciences, Taizhou, China.

    • Yajun Yang
    •  & Li Jin
  37. State Key Laboratory of Oncogene and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

    • Qijun Wu
  38. Department of Cancer Prevention and Control, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China.

    • Peng Peng
    •  & Ying Zheng
  39. Institute of Dermatology and Department of Dermatology, No. 1 Hospital, Anhui Medical University, Hefei, China.

    • Xiaodong Zheng
    •  & Xuejun Zhang
  40. State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Hefei, China.

    • Xiaodong Zheng
    •  & Xuejun Zhang
  41. Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China.

    • Yongbing Xiang
  42. Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Division of Epidemiology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.

    • Jirong Long
    • , Xiao-Ou Shu
    •  & Wei Zheng
  43. Cancer Prevention Institute of California, Fremont, California, USA.

    • Ann Hsing
  44. Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.

    • Jianyu Rao
  45. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

    • Fredirik Wiklund
    •  & Henrik Gronberg
  46. School of Public Health, Shanghai Jiaotong University, Shanghai, China.

    • Rong Shi

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Contributions

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.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Yinghao Sun.

Supplementary information

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DOI

https://doi.org/10.1038/ng.2424

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