A Genome-wide Association Study of Lung Cancer Identifies a Region of Chromosome 5p15 Associated with Risk for Adenocarcinoma

Maria Teresa Landi, Nilanjan Chatterjee, Kai Yu, Lynn R. Goldin, Alisa M. Goldstein, Melissa Rotunno, Lisa Mirabello, Kevin Jacobs, William Wheeler, Meredith Yeager, Andrew W. Bergen, Qizhai Li, Dario Consonni, Angela C. Pesatori, Sholom Wacholder, Michael Thun, Ryan Diver, Martin Oken, Jarmo Virtamo, Demetrius AlbanesZhaoming Wang, Laurie Burdette, Kimberly F. Doheny, Elizabeth W. Pugh, Cathy Laurie, Paul Brennan, Rayjean Hung, Valerie Gaborieau, James D. McKay, Mark Lathrop, John McLaughlin, Ying Wang, Ming Sound Tsao, Margaret R. Spitz, Yufei Wang, Hans Krokan, Lars Vatten, Frank Skorpen, Egil Arnesen, Simone Benhamou, Christine Bouchard, Andres Metsapalu, Tonu Vooder, Mari Nelis, Kristian Välk, John K. Field, Chu Chen, Gary Goodman, Patrick Sulem, Gudmar Thorleifsson, Thorunn Rafnar, Timothy Eisen, Wiebke Sauter, Albert Rosenberger, Heike Bickeböller, Angela Risch, Jenny Chang-Claude, H. Erich Wichmann, Kari Stefansson, Richard Houlston, Christopher I. Amos, Joseph F. Fraumeni, Sharon A. Savage, Pier Alberto Bertazzi, Margaret A. Tucker, Stephen Chanock, Neil E. Caporaso

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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 = 3.02 × 10-7), 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 = 3.74 × 10-14 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.

Original languageEnglish (US)
Pages (from-to)679-691
Number of pages13
JournalAmerican journal of human genetics
Volume85
Issue number5
DOIs
StatePublished - Nov 13 2009

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ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Landi, M. T., Chatterjee, N., Yu, K., Goldin, L. R., Goldstein, A. M., Rotunno, M., Mirabello, L., Jacobs, K., Wheeler, W., Yeager, M., Bergen, A. W., Li, Q., Consonni, D., Pesatori, A. C., Wacholder, S., Thun, M., Diver, R., Oken, M., Virtamo, J., ... Caporaso, N. E. (2009). A Genome-wide Association Study of Lung Cancer Identifies a Region of Chromosome 5p15 Associated with Risk for Adenocarcinoma. American journal of human genetics, 85(5), 679-691. https://doi.org/10.1016/j.ajhg.2009.09.012