Abstract

We conducted a genome-wide association study of gastric cancer and esophageal squamous cell carcinoma (ESCC) in ethnic Chinese subjects in which we genotyped 551,152 SNPs. We report a combined analysis of 2,240 gastric cancer cases, 2,115 ESCC cases and 3,302 controls drawn from five studies. In logistic regression models adjusted for age, sex and study, multiple variants at 10q23 had genome-wide significance for gastric cancer and ESCC independently. A notable signal was rs2274223, a nonsynonymous SNP located in PLCE1, for gastric cancer (P = 8.40 × 10−9; per-allele odds ratio (OR) = 1.31) and ESCC (P = 3.85 × 10−9; OR = 1.34). The association with gastric cancer differed by anatomic subsite. For tumors in the cardia the association was stronger (P = 4.19 × 10−15; OR = 1.57), and for those in the noncardia stomach it was absent (P = 0.44; OR = 1.05). Our findings at 10q23 could provide insight into the high incidence of both cancers in China.

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Acknowledgements

We thank the study participants and staff of the Shanghai Men's Health Study (SMHS), Shanghai Women's Health Study (SWHS) and Singapore Chinese Health Study (SCHS). Supported by the National Cancer Institute (SMHS: R01 CA82729; SWHS: R37 CA70837 and contract NO2-CP-11010 with Vanderbilt University; SCHS: R01 CA55069, R35 CA53890, R01 CA80205 and R01 CA144034). We thank M.C. Yu and H.-P. Lee for establishing this cohort. Cancer cases were identified through database linkage by the Ministry of Health in Singapore. The Shanxi Upper Gastrointestinal Cancer Genetics Project was supported by the National Cancer Institute contract NO2-SC-66211 with the Shanxi Cancer Hospital and Institute. The Nutrition Intervention Trials (NIT) were supported by National Cancer Institute contracts NO1-SC-91030 and HHSN261200477001C with the Cancer Institute of the Chinese Academy of Medical Sciences. The current analysis was supported by the Intramural Research Program of the NIH, National Cancer Institute, the Division of Cancer Epidemiology and Genetics, and the Center for Cancer Research.

Author information

Author notes

    • Christian C Abnet
    • , Neal D Freedman
    •  & Nan Hu

    These authors contributed equally to this work.

Affiliations

  1. Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health, Bethesda, Maryland, USA.

    • Christian C Abnet
    • , Neal D Freedman
    • , Nan Hu
    • , Zhaoming Wang
    • , Kai Yu
    • , Sanford M Dawsey
    • , Linda M Dong
    • , Chaoyu Wang
    • , Mitchell H Gail
    • , Meredith Yeager
    • , Jeff Yuenger
    • , Amy Hutchinson
    • , Kevin B Jacobs
    • , Laurie Burdett
    • , Joseph F Fraumeni Jr
    • , Margaret A Tucker
    • , Wong-Ho Chow
    • , Alisa M Goldstein
    • , Stephen J Chanock
    •  & Philip R Taylor
  2. Core Genotyping Facility, NCI-Frederick, SAIC-Frederick Inc., Frederick, Maryland, USA.

    • Zhaoming Wang
    • , Meredith Yeager
    • , Jeff Yuenger
    • , Amy Hutchinson
    • , Kevin B Jacobs
    •  & Laurie Burdett
  3. Department of Medicine and Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee, USA.

    • Xiao-Ou Shu
    •  & Wei Zheng
  4. Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA.

    • Jian-Min Yuan
  5. Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.

    • Maxwell P Lee
  6. Shanxi Cancer Hospital, Taiyuan, Shanxi, People's Republic of China.

    • Ti Ding
    •  & Ze-Zhong Tang
  7. Department of Epidemiology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Beijing, People's Republic of China.

    • You-Lin Qiao
    •  & Jin-Hu Fan
  8. Shanghai Cancer Institute, Shanghai, People's Republic of China.

    • Yu-Tang Gao
    •  & Yong-Bing Xiang
  9. Department of Epidemiology and Public Health, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

    • Woon-Puay Koh
  10. Information Management Services Inc., Silver Spring, Maryland, USA.

    • William Wheeler
    •  & Carol A Giffen

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Contributions

C.C.A., N.D.F., N.H., Z.W., K.Y., X.-O.S., J-M.Y., W.Z., L.M.D., W.-H.C., A.M.G., S.J.C. and P.R.T. organized and designed the study and served as the study steering committee. M.Y., J.Y., A.H., K.B.J., L.B., M.A.T. and S.J.C. supervised genotyping of samples. C.C.A., N.D.F., Z.W., K.Y., W.W., M.H.G., W.-H.C., A.M.G., S.J.C. and P.R.T. contributed to the design and execution of statistical analysis. C.C.A., Z.W. and S.J.C. wrote the first draft of the manuscript. C.C.A., N.H., X.-O.S., J.-M.Y., W.Z., S.M.D., M.P.L., T.D., Y.-L.Q., Y.-T.G., W.-P.K., Y.-B.X., Z.-Z.T., J.-H.F., C.W., C.A.G., J.F.F., W.-H.C., A.M.G. and P.R.T. conducted the epidemiologic studies and contributed samples to the GWAS and/or second phase. All authors contributed to writing the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Christian C Abnet.

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DOI

https://doi.org/10.1038/ng.649

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