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Title: A genome-wide association study of lung cancer identifies a region of chromosome 5p15 associated with risk for adenocarcinoma.
Authors: Landi MT,  Chatterjee N,  Yu K,  Goldin LR,  Goldstein AM,  Rotunno M,  Mirabello L,  Jacobs K,  Wheeler W,  Yeager M,  Bergen AW,  Li Q,  Consonni D,  Pesatori AC,  Wacholder S,  Thun M,  Diver R,  Oken M,  Virtamo J,  Albanes D,  Wang Z,  Burdette L,  Doheny KF,  Pugh EW,  Laurie C,  Brennan P,  Hung R,  Gaborieau V,  McKay JD,  Lathrop M,  McLaughlin J,  Wang Y,  Tsao MS,  Spitz MR,  Wang Y,  Krokan H,  Vatten L,  Skorpen F,  Arnesen E,  Benhamou S,  Bouchard C,  Metspalu A,  Vooder T,  Nelis M,  Välk K,  Field JK,  Chen C,  Goodman G,  Sulem P,  Thorleifsson G,  Rafnar T,  Eisen T,  Sauter W,  Rosenberger A,  Bickeböller H,  Risch A,  Chang-Claude J,  Wichmann HE,  Stefansson K,  Houlston R,  Amos CI,  Fraumeni JF Jr,  Savage SA,  Bertazzi PA,  Tucker MA,  Chanock S,  Caporaso NE
Journal: Am J Hum Genet
Date: 2009 Nov
PubMed ID: 19836008
PMC ID: PMC2775843
Abstract: Three genetic loci for lung cancer risk have been identified by genome-wide association studies (GWAS), but inherited susceptibility to specific histologic types of lung cancer is not well established. We conducted a GWAS of lung cancer and its major histologic types, genotyping 515,922 single-nucleotide polymorphisms (SNPs) in 5739 lung cancer cases and 5848 controls from one population-based case-control study and three cohort studies. Results were combined with summary data from ten additional studies, for a total of 13,300 cases and 19,666 controls of European descent. Four studies also provided histology data for replication, resulting in 3333 adenocarcinomas (AD), 2589 squamous cell carcinomas (SQ), and 1418 small cell carcinomas (SC). In analyses by histology, rs2736100 (TERT), on chromosome 5p15.33, was associated with risk of adenocarcinoma (odds ratio [OR]=1.23, 95% confidence interval [CI]=1.13-1.33, p=3.02x10(-7)), but not with other histologic types (OR=1.01, p=0.84 and OR=1.00, p=0.93 for SQ and SC, respectively). This finding was confirmed in each replication study and overall meta-analysis (OR=1.24, 95% CI=1.17-1.31, p=3.74x10(-14) for AD; OR=0.99, p=0.69 and OR=0.97, p=0.48 for SQ and SC, respectively). Other previously reported association signals on 15q25 and 6p21 were also refined, but no additional loci reached genome-wide significance. In conclusion, a lung cancer GWAS identified a distinct hereditary contribution to adenocarcinoma.