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Genome-wide association study identifies five loci associated with susceptibility to pancreatic cancer in Chinese populations

Nature Genetics volume 44, pages 62–66 (2012)Cite this article

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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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Figure 1: Manhattan plot of genome-wide P values of association.
Figure 2: Regional plots of association results and recombination rates within six significantly associated susceptibility loci .
Figure 3: Odds ratio for pancreatic cancer versus number of risk genotypes.

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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

  1. Chen Wu and Xiaoping Miao: These authors contributed equally to this work.

  2. Chengfeng Wang and Dongxin Lin: These authors jointly directed this work.

Authors and 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

Authors
  1. Chen Wu
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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.).

Corresponding authors

Correspondence to Chengfeng Wang or Dongxin Lin.

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The authors declare no competing financial interests.

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Wu, C., Miao, X., Huang, L. et al. Genome-wide association study identifies five loci associated with susceptibility to pancreatic cancer in Chinese populations. Nat Genet 44, 62–66 (2012). https://doi.org/10.1038/ng.1020

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