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Genome-wide association analysis identifies new lung cancer susceptibility loci in never-smoking women in Asia

Abstract

To identify common genetic variants that contribute to lung cancer susceptibility, we conducted a multistage genome-wide association study of lung cancer in Asian women who never smoked. We scanned 5,510 never-smoking female lung cancer cases and 4,544 controls drawn from 14 studies from mainland China, South Korea, Japan, Singapore, Taiwan and Hong Kong. We genotyped the most promising variants (associated at P < 5 × 10−6) in an additional 1,099 cases and 2,913 controls. We identified three new susceptibility loci at 10q25.2 (rs7086803, P = 3.54 × 10−18), 6q22.2 (rs9387478, P = 4.14 × 10−10) and 6p21.32 (rs2395185, P = 9.51 × 10−9). We also confirmed associations reported for loci at 5p15.33 and 3q28 and a recently reported finding at 17q24.3. We observed no evidence of association for lung cancer at 15q25 in never-smoking women in Asia, providing strong evidence that this locus is not associated with lung cancer independent of smoking.

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Figure 1: Association results from a GWAS of never-smoking women in Asia.
Figure 2: Association results, recombination hotspots and LD plots for the regions newly associated with lung cancer in never-smoking Asian females.

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Acknowledgements

We thank J.-J. Yang, X.-N. Yang, Q. Zhou, W.-B. Guo, S.-L. Chen, Y. Huang, Z. Xie, J.-G. Chen, H.-H. Yan, K. Tajima, Y. Yatabe, T. Hida, K.-L. Chuah, A. Ng, P. Eng, S.-S. Leong, M.-K. Ang, E. Lim, T.-K. Lim, M. Teh, W.-T. Poh and A. Tee. The overall GWAS project was supported by the intramural program of the US National Institutes of Health/National Cancer Institute. A list of support provided to individual studies is provided in the Supplementary Note.

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Q.L., N.R., S.J.C., D. Lin, C.A.H., Y.-C.H., K.M., A.S., H.D.H., J.Y.P., C.-J.C., Y.H.K., Y.T.K., C.L., Y.-L.W., P.-C.Y., B.Z., M.-H.S., J.F.F., K.C., W.Z., T.W., H.S., I.-S.C., D. Lu, N. Caporaso, W.P., R.K., J. Liu, M.T.L., N. Chatterjee, M.T. and M.Y. organized and designed the study. S.J.C., D. Lin, R.K., J. Liu, C.A.H., K.M., T.W., L.B., M.Y., J. Yuenger, Z.Y., C.W., H.G., A.H., W.W., Y.L., W.P., H.-C.L. and B.Z. conducted and supervised the genotyping of samples. Z.W., K.B.J., N.R., Q.L., S.J.C., N. Chatterjee, C.A.H., H.D.H., W.H., M.Y., I.-S.C., C.-F.H., W.-C.W., C.C.C., S.I.B., C.-H.C., R.V. and Y.-H.C. contributed to the design and execution of statistical analysis. Q.L., N.R., S.J.C., Z.W., W.H., C.C.C., C.A.H., K.M., Y.-C.H., A.S., H.D.H., N. Chatterjee, N. Caporaso, C.L., M.Y., B.A.B., M.T., S.-J.A., S.I.B., M.T.L., C.K., R.V., Y.-L.W., J.F.F. and I.-S.C. wrote the first draft of the manuscript. C.A.H., Q.L., B.Z., Y.-C.H., K.M., A.S., K.C., J.-C.W., M.P.W., W.Z., J.Y.P., W.H., C.-J.C., Y.H.K., Y.T.K., T.W., H.S., I.-S.C., T.M., H.N.K., F.W., Z.Y., C.W., S.-J.A., G.-C.C., B.Q., V.H.F.L., D. Lu, H.-S.J., J.S.S., J.H.K., Y.-T.G., Y.-H.T., Y.J.J., H.G., Z.H., I.-J.O., K.-Y.C., X.H., W.W., J.C., X.-C.Z., M.-S.H., H.Z., J. Wang, X.Z., J.E.C., W.-C.S., K.H.P., S.W.S., X.-O.S., Y.-M.C., L.L., C.H.K., L.H., Y.-C.K., T.-Y.Y., J.X., P.G., W.T., J.S., C.-L.W., H.L., A.D.L.S., Z.Z., Y.C., Y.Y.C., J.-Y.H., J.S.K., H.-I.Y., Q.C., C.-C.L., I.K.P., P.X., J.D., Q.H., R.-P.P., T.K., S.-S.K., C.-Y.C., R.V., J. Wu, W.-Y.L., K.-C.C., W.-H.C., B.-T.J., J.K.C.C., M.C., Y.-J.L., J. Yokota, J. Li, H.C., Y.-B.X., C.-J.Y., H.K., G.W., L.J., Y.-L.L., K.S., Y.-L.W., P.-C.Y., M.-H.S., J.F.F., D. Lin, S.J.C. and N.R. conducted the epidemiological studies and contributed samples to the GWAS and/or follow-up genotyping. All authors contributed to the writing of the manuscript.

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Correspondence to Qing Lan.

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Lan, Q., Hsiung, C., Matsuo, K. et al. Genome-wide association analysis identifies new lung cancer susceptibility loci in never-smoking women in Asia. Nat Genet 44, 1330–1335 (2012). https://doi.org/10.1038/ng.2456

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