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PMID: 19836008 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

A genome-wide association study of lung cancer identifies a region of chromosome 5p15 associated with risk for adenocarcinoma.

American journal of human genetics ·Vol. 85 ·No. 5 ·2009-00-00 ·Pages 679-91

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, Metsapalu 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, Savage SA, Bertazzi PA, Tucker MA, Chanock S, Caporaso NE

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.

MeSH Terms
Adenocarcinoma/genetics Case-Control Studies Chromosomes, Human, Pair 5/genetics Cohort Studies Genetic Predisposition to Disease Genetic Variation Genome-Wide Association Study Genotype Humans Linkage Disequilibrium Lung Neoplasms/genetics Meta-Analysis as Topic Odds Ratio Polymorphism, Single Nucleotide Risk Factors Whites/genetics
Authors & Affiliations
68 authors, click to expand affiliations / ORCID
Landi Maria Teresa
Division of Cancer Epidemiology, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA. [email protected]
Chatterjee Nilanjan
Yu Kai
Goldin Lynn R
Goldstein Alisa M
Rotunno Melissa
Mirabello Lisa
Jacobs Kevin
Wheeler William
Yeager Meredith
Bergen Andrew W
Li Qizhai
Consonni Dario
Pesatori Angela C
Wacholder Sholom
Thun Michael
Diver Ryan
Oken Martin
Virtamo Jarmo
Albanes Demetrius
Wang Zhaoming
Burdette Laurie
Doheny Kimberly F
Pugh Elizabeth W
Laurie Cathy
Brennan Paul
Hung Rayjean
Gaborieau Valerie
McKay James D
Lathrop Mark
McLaughlin John
Wang Ying
Tsao Ming-Sound
Spitz Margaret R
Wang Yufei
Krokan Hans
Vatten Lars
Skorpen Frank
Arnesen Egil
Benhamou Simone
Bouchard Christine
Metspalu Andres
Metsapalu Andres
Vooder Tonu
Nelis Mari
Välk Kristian
Field John K
Chen Chu
Goodman Gary
Sulem Patrick
Thorleifsson Gudmar
Rafnar Thorunn
Eisen Timothy
Sauter Wiebke
Rosenberger Albert
Bickeböller Heike
Risch Angela
Chang-Claude Jenny
Wichmann H Erich
Stefansson Kari
Houlston Richard
Amos Christopher I
Fraumeni Joseph F
Savage Sharon A
Bertazzi Pier Alberto
Tucker Margaret A
Chanock Stephen
Caporaso Neil E
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Article Info
Journal
American journal of human genetics
Abbr.
Am J Hum Genet
ISSN
1537-6605
DOI
10.1016/j.ajhg.2009.09.012
Email
[email protected]
Published
2009-00-00
Epub
2009-00-15
Pages
679-91
Language
English
Region
United States
NLM ID
0370475
PMCID
PMC2775843
Subset
IM
Grants
Medical Research Council · G9900432 · United Kingdom
NCI NIH HHS · R01 CA127219 · United States
NCI NIH HHS · R01 CA127219-02 · United States
NCI NIH HHS · R01 CA127219-04 · United States
Corrections
ErratumIn
PMID: 28472664
External Links
PubMed source DOI: 10.1016/j.ajhg.2009.09.012 PMC Full Text View journal details
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