Abstract
Esophageal squamous-cell carcinoma (ESCC) is one of the most prevalent cancers worldwide and occurs at a relatively high frequency in China. To identify genetic susceptibility loci for ESCC, we conducted a genome-wide association study on 2,031 individuals with ESCC (cases) and 2,044 controls of Chinese descent using 666,141 autosomal SNPs. We evaluated promising associations in an additional 6,276 cases and 6,165 controls of Chinese descent from different areas of China. We identified seven susceptibility loci on chromosomes 5q11, 6p21, 10q23, 12q24 and 21q22 (ranging from P = 7.48 × 10−12 to P = 2.44 × 10−31); among these loci, 5q11, 6p21 and 21q22 were newly identified. Three variants in high linkage disequilibrium on 12q24 confer their risks to ESCC in a gene-lifestyle interaction manner, with more pronounced risk enhancement seen in tobacco and alcohol users. Furthermore, the identified variants had a cumulative association with ESCC risk (Ptrend = 7.92 × 10−56). These findings highlight the involvement of multiple genetic loci and gene-environment interaction in the development of esophageal cancer.
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Acknowledgements
We would like to thank Y. Li of University of North Carolina for her help in imputation analysis and helpful review of the manuscript. This work is funded by the National High-Tech Research and Development Program of China (2009AA022706 to D.L.), National Basic Research Program of China (2011CB504303 to D.L. and W.T.) and the National Natural Science Foundation of China (30721001 to Q.Z., D.L. and Z.L.).
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D.L. was the overall study principal investigator who conceived the study and obtained financial support and was responsible for study design, oversaw the entire study, interpreted the results and wrote parts of and synthesized the paper. C.W. performed overall project management, oversaw laboratory analyses and statistical analyses and drafted the initial manuscript. Z. Hu, G.J. and H.S. were responsible for subject recruitment and sample preparation of Nanjing samples. Z. He, C.G. and Y.K. were responsible for subject recruitment and sample preparation of the Anyang samples. W.J., J.F. and Y. Zeng were responsible for subject recruitment and sample preparation of Guangzhou samples. F.W. and T.W. provided some of the control samples. Y. Zhou was responsible for subject recruitment and sample preparation of the additional independent validation cohort. D.Y., K.Z., J.C., Y.Q. and W.T. performed subject recruitment and sample preparation of the Beijing samples. Y.L., X.M., Zhe Liu and Y.S. performed statistical analyses. Q.Z. and Zhihua Liu provided financial support and reviewed the manuscript.
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Wu, C., Hu, Z., He, Z. et al. Genome-wide association study identifies three new susceptibility loci for esophageal squamous-cell carcinoma in Chinese populations. Nat Genet 43, 679–684 (2011). https://doi.org/10.1038/ng.849
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DOI: https://doi.org/10.1038/ng.849
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