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Common 5p15.33 and 6p21.33 variants influence lung cancer risk


We conducted a genome-wide association (GWA) study of lung cancer comparing 511,919 SNP genotypes in 1,952 cases and 1,438 controls. The most significant association was attained at 15q25.1 (rs8042374; P = 7.75 × 10−12), confirming recent observations. Pooling data with two other GWA studies (5,095 cases, 5,200 controls) and with replication in an additional 2,484 cases and 3,036 controls, we identified two newly associated risk loci mapping to 6p21.33 (rs3117582, BAT3-MSH5; Pcombined = 4.97 × 10−10) and 5p15.33 (rs401681, CLPTM1L; Pcombined = 7.90 × 10−9).

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Figure 1: Summary of association results for rs3117582 and rs401681.
Figure 2: LD structure and association results for the two confirmed lung cancer–associated regions.

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Cancer Research UK (A1298/A8780) provided principal funding for this study. Additional funding was provided by HEAL and Sanofi-Aventis and US NIH Grants P50CA70907, R01CA121197 and R01CA133996. We would like to thank all individuals who participated in this study. We are grateful to colleagues at UK Clinical Genetics Centres and the UK National Cancer Research Network.

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Authors and Affiliations



R.S.H. designed the study, with substantial contributions from C.I.A. and T.E. R.S.H. drafted the manuscript, with substantial contributions from E.W. and C.I.A. T.E., R.S.H. and A.M. oversaw sample and data collection of cases for the UK study. P.B. oversaw the genotyping for the UK study. P.B. managed samples for the UK study. J.V. and M.Q. performed sample preparation for the UK study. Y.W. performed statistical and bioinformatics analyses for the UK study. Y.W. and E.W. performed statistical and bioinformatics analyses for the meta-analysis. M.R.S. oversaw sample and data collection of cases for the Texas study. C.I.A. oversaw the GWA genotyping and analyses for the Texas Study. X.W. managed samples for the Texas study. X.G., W.V.C. and Q.D. performed analyses and curated data for the Texas study. All authors contributed to the final paper.

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Correspondence to Richard S Houlston.

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Supplementary Figures 1–3, Supplementary Table 2 and Supplementary Methods (PDF 664 kb)

Supplementary Table 1

Meta-analysis results (XLS 96 kb)

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Wang, Y., Broderick, P., Webb, E. et al. Common 5p15.33 and 6p21.33 variants influence lung cancer risk. Nat Genet 40, 1407–1409 (2008).

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