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

被引：445

作者：

Landi, Maria Teresa ^{[1
]}

Chatterjee, Nilanjan ^{[1
]}

Yu, Kai ^{[1
]}

Goldin, Lynn R. ^{[1
]}

Goldstein, Alisa M. ^{[1
]}

Rotunno, Melissa ^{[1
]}

Mirabello, Lisa ^{[1
]}

Jacobs, Kevin ^{[1
]}

Wheeler, William ^{[2
]}

Yeager, Meredith ^{[1
]}

Bergen, Andrew W. ^{[3
]}

Li, Qizhai ^{[1
,4
]}

Consonni, Dario ^{[5
,6
]}

Pesatori, Angela C. ^{[5
,6
]}

Wacholder, Sholom ^{[1
]}

Thun, Michael ^{[7
]}

Diver, Ryan ^{[7
]}

Oken, Martin ^{[8
]}

Virtamo, Jarmo ^{[9
]}

Albanes, Demetrius ^{[1
]}

Wang, Zhaoming ^{[1
]}

Burdette, Laurie ^{[1
]}

Doheny, Kimberly F. ^{[10
]}

Pugh, Elizabeth W. ^{[10
]}

Laurie, Cathy ^{[11
]}

Brennan, Paul ^{[12
]}

Hung, Rayjean ^{[13
]}

Gaborieau, Valerie ^{[12
]}

McKay, James D. ^{[12
]}

Lathrop, Mark ^{[14
]}

McLaughlin, John ^{[13
]}

Wang, Ying ^{[13
]}

Tsao, Ming-Sound ^{[15
]}

Spitz, Margaret R. ^{[16
]}

Wang, Yufei ^{[17
]}

Krokan, Hans ^{[18
]}

Vatten, Lars ^{[18
]}

Skorpen, Frank ^{[18
]}

Arnesen, Egil ^{[19
]}

Benhamou, Simone ^{[14
,20
]}

Bouchard, Christine ^{[21
]}

Metsapalu, Andres ^{[22
,23
]}

Vooder, Tonu ^{[22
,23
]}

Nelis, Mari ^{[22
,23
]}

Vaelk, Kristian ^{[22
,23
]}

Field, John K. ^{[24
]}

Chen, Chu ^{[25
]}

Goodman, Gary ^{[25
]}

Sulem, Patrick ^{[26
]}

Thorleifsson, Gudmar ^{[26
]}

机构：

[1] NCI, Div Canc Epidemiol, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA

[2] Informat Management Serv Inc, Rockville, MD 20852 USA

[3] SRI Int, Ctr Hlth Sci, Mol Genet program, Menlo Pk, CA 94025 USA

[4] Chinese Acad Sci, Acad Math & Syst Sci, Key Lab Syst & Control, Beijing 100190, Peoples R China

[5] Osped Maggiore Policlin Mangiagalli & Regina Elen, Fdn Ist Ricevero & Cura Carattere Sci, Epidemiol Unit, I-20122 Milan, Italy

[6] Univ Milan, Dept Occupat & Environm Hlth, I-20122 Milan, Italy

[7] Amer Canc Soc Epidemiol & Surveillance Res, Atlanta, GA 30301 USA

[8] Univ Minnesota, Hubert H Humphrey Canc Ctr, Minneapolis, MN 55455 USA

[9] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki 00280, Finland

[10] Johns Hopkins Univ, Sch Med, Inst Med Genet, Ctr Inherited Dis Res, Baltimore, MD 21224 USA

[11] Univ Washington, Dept Biostat, Seattle, WA 98195 USA

[12] Int Agcy Res Canc, F-69372 Lyon, France

[13] Univ Toronto, Dalla Lana Sch Publ Hlth, Div Epidemiol, Samuel Lunenfeld Res Inst, Toronto, ON M5T 3L9, Canada

[14] Fdn Jean Dausset, Ctr Etud Polymorphisme Humain, F-75010 Paris, France

[15] Princess Margaret Hosp, Univ Hlth Network, Dept Pathol, Toronto, ON M5T 3L9, Canada

[16] Univ Texas Houston, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA

[17] Inst Canc Res, Sect Canc Genet, Sutton SM2 5NG, Surrey, England

[18] Norwegian Univ Sci & Technol, Fac Med, N-7489 Trondheim, Norway

[19] Univ Tromso, Dept Community Med, N-9037 Tromso, Norway

[20] INSERM, F-75010 Paris, France

[21] Geneva Canc Registry, CH-1205 Geneva, Switzerland

[22] Univ Tartu, Inst Mol & Cell Biol, Estonian Bioctr, EE-51010 Tartu, Estonia

[23] Univ Tartu, Estonian Genome Project, Estonian Bioctr, EE-51010 Tartu, Estonia

[24] Univ Liverpool, Canc Res Ctr, Roy Castle Lung Canc Res Program, Liverpool L3 97A, Merseyside, England

[25] Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, Seattle, WA 98109 USA

[26] DeCODE Genet, IS-101 Reykjavik, Iceland

[27] Univ Cambridge, Dept Oncol, Cambridge CB2 2RE, England

[28] German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Inst Epidemiol, D-85764 Neuherberg, Germany

[29] Univ Munich, Inst Med Informat Biometry & Epidemiol, Chair Epidemiol, D-81377 Munich, Germany

[30] Univ Munich, Klinikum Grosshadern, D-81377 Munich, Germany

[31] Univ Gottingen, Dept Genet Epidemiol, Sch Med, D-37073 Gottingen, Germany

[32] German Canc Res Ctr, Div Epigenom & Canc Risk Factors, D-69120 Heidelberg, Germany

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2009年 / 85卷 / 05期

基金：

英国医学研究理事会;

关键词：

TELOMERASE REVERSE-TRANSCRIPTASE; SUSCEPTIBILITY LOCUS; FAMILY-HISTORY; MUTATIONS; VARIANTS; EXPRESSION; TERT; SMOKERS; IMPACT; COHORT;

D O I：

10.1016/j.ajhg.2009.09.012

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Three genetic loci for lung cancer risk have been identified by genome-wide association studies (GWAS), but inherited susceptibility to specific histologic types of king 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 (SQ. 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 x 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 x 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.

引用

页码：679 / 691

页数：13

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