Abstract
Lung cancer is the leading cause of cancer-related deaths worldwide. To identify genetic factors that modify the risk of lung cancer in individuals of Chinese ancestry, we performed a genome-wide association scan in 5,408 subjects (2,331 individuals with lung cancer (cases) and 3,077 controls) followed by a two-stage validation among 12,722 subjects (6,313 cases and 6,409 controls). The combined analyses identified six well-replicated SNPs with independent effects and significant lung cancer associations (P < 5.0 × 10−8) located in TP63 (rs4488809 at 3q28, P = 7.2 × 10−26), TERT-CLPTM1L (rs465498 and rs2736100 at 5p15.33, P = 1.2 × 10−20 and P = 1.0 × 10−27, respectively), MIPEP-TNFRSF19 (rs753955 at 13q12.12, P = 1.5 × 10−12) and MTMR3-HORMAD2-LIF (rs17728461 and rs36600 at 22q12.2, P = 1.1 × 10−11 and P = 6.2 × 10−13, respectively). Two of these loci (13q12.12 and 22q12.2) were newly identified in the Chinese population. These results suggest that genetic variants in 3q28, 5p15.33, 13q12.12 and 22q12.2 may contribute to the susceptibility of lung cancer in Han Chinese.
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Acknowledgements
This work is funded by the China National High-Tech Research and Development Program Grant (2009AA022705, 2009AA022701) and partly funded by the National Key Basic Research Program Grant (2011CB503805), the National Natural Science Foundation of China (30730080, 30972541, 30901233 and 30872178) and a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions. The authors wish to thank all the study participants, research staff and students who participated in this work. We thank C. Amos, J. Xu and Q. Wei for their manuscript editing.
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H.S. directed the study, obtained financial support and was responsible for study design, interpretation of results and manuscript writing. Z.H. performed overall project management, statistical analyses with J.D. and drafted the initial manuscript. D. Lin, T.W., Y.S., D. Lu., J.L., B.Z., X.W. and L.J. directed each participating study and jointly organized this study. L.H., Y.J., M.C., J.C. and F.L. were responsible for sample processing and managing the genotyping data. Y.C., Y.S., L.X., G.J., Z.Z. and H.M. were responsible for subject recruitment and sample preparation of Nanjing samples. X.L., C.W., W.T. and D.Y. were responsible for subject recruitment and sample preparation of Beijing samples. L.L., P.X., H.G. and Q.D. were responsible for subject recruitment and sample preparation of Wuhan samples. B.H., C.B., Z.L., X.Z., G.Z., J.W. and H.C. were responsible for subject recruitment and sample preparation of Shanghai samples. Y.Z., H.Z., Y.Y., Z.Y., W.W. and P.G. were responsible for subject recruitment and sample preparation of Shenyang samples. L.Y. was responsible for subject recruitment and sample preparation of Guangzhou samples. F.C. oversaw the statistical analyses process. All authors approved the final manuscript.
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Hu, Z., Wu, C., Shi, Y. et al. A genome-wide association study identifies two new lung cancer susceptibility loci at 13q12.12 and 22q12.2 in Han Chinese. Nat Genet 43, 792–796 (2011). https://doi.org/10.1038/ng.875
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DOI: https://doi.org/10.1038/ng.875
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