Abstract

Pancreatic cancer has the lowest survival rate among human cancers, and there are no effective markers for its screening and early diagnosis. To identify genetic susceptibility markers for this cancer, we carried out a genome-wide association study on 981 individuals with pancreatic cancer (cases) and 1,991 cancer-free controls of Chinese descent using 666,141 autosomal SNPs. Promising associations were replicated in an additional 2,603 pancreatic cancer cases and 2,877 controls recruited from 25 hospitals in 16 provinces or cities in China. We identified five new susceptibility loci at chromosomes 21q21.3, 5p13.1, 21q22.3, 22q13.32 and 10q26.11 (P = 2.24 × 10−13 to P = 4.18 × 10−10) in addition to 13q22.1 previously reported in populations of European ancestry. These results advance our understanding of the development of pancreatic cancer and highlight potential targets for the prevention or treatment of this cancer.

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Acknowledgements

This work was supported by grants from the National High-Tech Research and Development Program of China (2009AA022706) and the National Natural Science Foundation of China (81021061) to D.L. We thank L. Liang for help in eQTL analysis. We also thank the subjects and the surgeons who recruited them; M. Yang, L. Wang, X. Wang, C. Yang, L. Du, J. Li, F. Qi, X. Song and L. Zeng.

Author information

Author notes

    • Chen Wu
    •  & Xiaoping Miao

    These authors contributed equally to this work.

    • Chengfeng Wang
    •  & Dongxin Lin

    These authors jointly directed this work.

Affiliations

  1. State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

    • Chen Wu
    • , Liming Huang
    • , Dianke Yu
    • , Kan Zhai
    • , Jiang Chang
    • , Yu Liu
    • , Jian Xu
    • , Wen Tan
    •  & Dongxin Lin
  2. Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, China.

    • Xiaoping Miao
    •  & Tangchun Wu
  3. Department of Abdominal Surgery, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

    • Xu Che
    • , Ping Zhao
    •  & Chengfeng Wang
  4. Department of Radiation Oncology, Cancer Hospital, Fudan University, Shanghai, China.

    • Guoliang Jiang
  5. Department of Pathology, Shengjing Hospital, China Medical University, Shenyang, China.

    • Xianghong Yang
    • , Wanjin Dai
    • , Wei Cao
    •  & Ying Ma
  6. Department of Epidemiology, Second Military Medical University, Shanghai, China.

    • Guangwen Cao
  7. Department of Epidemiology and Biostatistics, Cancer Center, Nanjing Medical University, Nanjing, China.

    • Zhibin Hu
    •  & Hongbing Shen
  8. Department of Gastrointestinal Surgery, Union Hospital of Fujian Medical University, Fuzhou, China.

    • Yongjian Zhou
  9. Department of Gastroduodenal and Pancreatic Surgery, Hunan Province Tumor Hospital, Changsha, China.

    • Chaohui Zuo
  10. Union Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, China.

    • Chunyou Wang
  11. Department of Experimental Pathology, Hebei Medical University, Shijiazhuang, China.

    • Xianghong Zhang
  12. Laboratory of Cancer Molecular Genetics, Medical College of Soochow University, Suzhou, China.

    • Yifeng Zhou
  13. Department of Pancreas and Hepatobiliary Surgery, Cancer Hospital, Fudan University, Shanghai, China.

    • Xianjun Yu
  14. Department of Gastroenterology, First Affiliated Hospital, Second Military Medical University, Shanghai, China.

    • Zhaoshen Li
    •  & Jun Gao
  15. Department of Integrative Oncology, Cancer Hospital, Fudan University, Shanghai, China.

    • Luming Liu
  16. Department of Hepatobiliary and Pancreatic Surgery, Union Hospital of Fujian Medical University, Fuzhou, China.

    • Yanling Chen
  17. Department of Pathology, First Affiliated Hospital of Fujian Medical University, Fuzhou, China.

    • Sheng Zhang
  18. Department of Surgery, The University of Hong Kong, Hong Kong, China.

    • Xiaoqi Wang
    •  & Siu Tim Cheung
  19. Department of Pathology, Cancer Hospital, Fudan University, Shanghai, China.

    • Menghong Sun
  20. Department of Pathology, Fujian Provincial Cancer Hospital, Fuzhou, China.

    • Xiongwei Zheng
  21. Department of Pathology, Affiliated Hospital, Inner Mongolia School of Medicine, Huhhot, Inner Mongolia.

    • Yongfeng Jia

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Contributions

D.L. conceived, designed and oversaw the study, obtained financial support, interpreted the results and wrote parts of and synthesized the paper. C. Wu managed the project, oversaw laboratory and statistical analyses and drafted the initial manuscript. Chengfeng Wang designed the study and oversaw pancreatic cancer patient recruitment. X.M. designed the study and carried out statistical analyses, subject recruitment and sample preparation of Zhejiang samples. L.H., K.Z., J.C. and J.X. prepared samples and did TaqMan genotyping. X.C., D.Y., Y.L., W.T. and P.Z. recruited subjects from Beijing, Shandong, Sichuan and Chongqing. Various authors recruited subjects and samples from Shanghai (G.J., G.C., X.Y., Z.L., L.L., M.S. and J.G.), Liaoning (X.Y., W.D., W.C. and Y.M.), Jiangsu (Z.H., H.S. and Yifeng Zhou), Fujian (Yongjian Zhou, Y.C., S.Z. and X. Zheng), Hunan (C.Z.), Hubei (Chunyou Wang and T.W.), Hebei (X. Zhang and Y.J.) and Hong Kong (X.W. and S.T.C.).

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Chengfeng Wang or Dongxin Lin.

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DOI

https://doi.org/10.1038/ng.1020

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