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