TY - JOUR
T1 - Influence of common genetic variation on lung cancer risk
T2 - Meta-analysis of 14 900 cases and 29 485 controls
AU - Timofeeva, Maria N.
AU - Hung, Rayjean J.
AU - Rafnar, Thorunn
AU - Christiani, David C.
AU - Field, John K.
AU - Bickeböller, Heike
AU - Risch, Angela
AU - Mckay, James D.
AU - Wang, Yufei
AU - Dai, Juncheng
AU - Gaborieau, Valerie
AU - Mclaughlin, John
AU - Brenner, Darren
AU - Narod, Steven A.
AU - Caporaso, Neil E.
AU - Albanes, Demetrius
AU - Thun, Michael
AU - Eisen, Timothy
AU - Wichmann, H. Erich
AU - Rosenberger, Albert
AU - Han, Younghun
AU - Chen, Wei
AU - Zhu, Dakai
AU - Spitz, Margaret
AU - Wu, Xifeng
AU - Pande, Mala
AU - Zhao, Yang
AU - Zaridze, David
AU - Szeszenia-dabrowska, Neonilia
AU - Lissowska, Jolanta
AU - Rudnai, Peter
AU - Fabianova, Eleonora
AU - Mates, Dana
AU - Bencko, Vladimir
AU - Foretova, Lenka
AU - Janout, Vladimir
AU - Krokan, Hans E.
AU - Gabrielsen, Maiken Elvestad
AU - Skorpen, Frank
AU - Vatten, Lars
AU - NjØlstad, Inger
AU - Chen, Chu
AU - Goodman, Gary
AU - Lathrop, Mark
AU - Benhamou, Simone
AU - Vooder, TÕnu
AU - Välk, Kristjan
AU - Nelis, Mari
AU - Metspalu, Andres
AU - Raji, Olaide
AU - Chen, Ying
AU - Gosney, John
AU - Liloglou, Triantafillos
AU - Muley, Thomas
AU - Dienemann, Hendrik
AU - Thorleifsson, Gudmar
AU - Shen, Hongbing
AU - Stefansson, Kari
AU - Brennan, Paul
AU - Amos, Christopher I.
AU - Houlston, Richard
AU - Landi, Maria Teresa
N1 - Funding Information:
This study was supported by the grant from the National Institute of Health (NIH) (U19CA148127). The SLRI study was supported by Canadian Cancer Society Research Institute (020214), Ontario Institute of Cancer and Cancer Care Ontario Chair Award to R.H. The ICR study was supported by Cancer Research UK (C1298/A8780 and C1298/A8362— Bobby Moore Fund for Cancer Research UK) and NCRN, HEAL and Sanofi-Aventis. Additional funding was obtained from NIH grants (5R01CA055769, 5R01CA127219, 5R01CA133996, and 5R01CA121197). The Liverpool Lung Project (LLP) was supported by The Roy Castle Lung Cancer Foundation, UK. The ICR and LLP studies made use of genotyping data from the Wellcome Trust Case Control Consortium 2 (WTCCC2); a full list of the investigators who contributed to the generation of the data is available from www.wtccc.org.uk. Sample collection for the Heidelberg lung cancer study was in part supported by a grant (70-2919) from the Deutsche Krebshilfe. The work was additionally supported by a Helmholtz-DAAD fellowship (A/07/97379 to M.N.T.) and by the National Institute of Health (USA) (U19CA148127). The KORA Surveys were financed by the GSF, which is funded by the German Federal Ministry of Education, Science, Research and Technology and the State of Bavaria. The LUng Cancer in the Young study (LUCY) was funded in part by the National Genome Research Network (NGFN), the DFG (BI 576/2-1; BI 576/2-2), the Helmholtzge-meinschaft (HGF) and the Federal office for Radiation Protection (BfS: STSch4454). Genotyping was performed in the Genome Analysis Center (GAC) of the Helmholtz Zentrum Muenchen. Support for the Central Europe, HUNT2/Tromsø and CARET genome-wide studies was provided by Institut National du Cancer, France. Support for the HUNT2/Tromsø genome-wide study was also provided by the European Community (Integrated Project DNA repair, LSHG-CT-2005-512113), the Norwegian Cancer Association and the Functional Genomics Programme of Research Council of Norway. Support for the Central Europe study, Czech Republic, was also provided by the European Regional Development Fund and the State Budget of the Czech Republic (RECAMO, CZ.1.05/2.1.00/03.0101). Support for the CARET genome-wide study was also provided by grants from the National Cancer Institute of the U.S. National Institutes of Health (R01 CA111703 and UO1 CA63673) and by funds from the Fred Hutchinson Cancer Research Center. Additional funding for study coordination, genotyping of replication studies and statistical analysis was provided by the US National Cancer Institute (R01 CA092039). The lung cancer GWAS from Estonia was partly supported by a FP7 grant (REGPOT 245536), by the Estonian Government (SF0180142s08), by EU RDF in the frame of Centre of Excellence in Genomics and Estoinian Research Infrastructure’s Roadmap and by University of Tartu (SP1GVARENG). The work reported in this paper was partly undertaken during the tenure of a Postdoctoral Fellowship from the IARC (for MNT). The Environment and Genetics in Lung Cancer Etiology (EAGLE), the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC) and the Prostate, Lung, Colon, Ovary Screening Trial (PLCO) studies and the genotyping of ATBC, the Cancer Prevention Study II Nutrition Cohort (CPS-II) and part of PLCO were supported by the Intramural Research Program of NIH, NCI, Division of Cancer Epidemiology and Genetics. ATBC was also supported by U.S. Public Health Service contracts (N01-CN-45165, N01-RC-45035 and N01-RC-37004) from the NCI. PLCO was also supported by individual contracts from the NCI to the University of Colorado Denver (NO1-CN-25514), Georgetown University (NO1-CN-25522), Pacific Health Research Institute (NO1- CN-25515), Henry Ford Health System (NO1-CN-25512), University of Minnesota (NO1-CN-25513), Washington University (NO1-CN-25516), University of Pittsburgh (NO1-CN-25511), University of Utah (NO1-CN-25524), Marshfield Clinic Research Foundation (NO1-CN-25518), University of Alabama at Birmingham (NO1-CN-75022, Westat, Inc. NO1-CN-25476), University of California, Los Angeles (NO1-CN-25404). The Cancer Prevention Study II Nutrition Cohort was supported by the American Cancer Society. The NIH Genes, Environment and Health Initiative (GEI) partly funded DNA extraction and statistical analyses (HG-06-033-NCI-01 and RO1HL091172-01), genotyping at the Johns Hopkins University Center for Inherited Disease Research (U01HG004438 and NIH HHSN268200782096C) and study coordination at the GENEVA Coordination Center (U01 HG004446) for EAGLE and part of PLCO studies. Funding for the MD Anderson Cancer Study was provided by NIH grants (P50 CA70907, R01CA121197, RO1 CA127219, U19 CA148127, RO1 CA55769) and CPRIT grant (RP100443). Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is funded through a federal contract from the National Institutes of Health to The Johns Hopkins University (HHSN268200782096C). The Harvard Lung Cancer Study was funded by Funded by National Institutes of Health (CA074386, CA092824, CA090578). The Nanjing study and Beijing studies were funded by the China National High-Tech Research and Development Program Grant (2009AA022705), the National Key Basic Research Program Grant (2011CB503805) and the National Natural Science Foundation of China (30730080, 30972541, 30901233 and 30872178). Funding to pay the Open Access publication charges for this article was provided by the grant from the National Institute of Health (NIH) (U19CA148127).
PY - 2012/11
Y1 - 2012/11
N2 - Recent genome-wide association studies (GWASs) have identified common genetic variants at 5p15.33, 6p21-6p22 and 15q25.1 associated with lung cancer risk. Several other genetic regions including variants of CHEK2 (22q12), TP53BP1 (15q15) and RAD52 (12p13) have been demonstrated to influence lung cancer risk in candidate- or pathway-based analyses. To identify novel risk variants for lung cancer, we performed a meta-analysis of 16 GWASs, totaling 14 900 cases and 29 485 controls of European descent. Our data provided increased support for previously identified risk loci at 5p15 (P = 7.2 × 10-16), 6p21 (P = 2.3 × 10-14) and 15q25 (P = 2.2 × 10-63). Furthermore, we demonstrated histology-specific effects for 5p15, 6p21 and 12p13 loci but not for the 15q25 region. Subgroup analysis also identified a novel disease locus for squamous cell carcinoma at 9p21 (CDKN2A/p16INK4A/p14ARF/CDKN2B/p15INK4B/ANRIL; rs1333040, P = 3.0 × 10-7) which was replicated in a series of 5415 Han Chinese (P = 0.03; combined analysis, P = 2.3 × 10-8). This large analysis provides additional evidence for the role of inherited genetic susceptibility to lung cancer and insight into biological differences in the development of the different histological types of lung cancer.
AB - Recent genome-wide association studies (GWASs) have identified common genetic variants at 5p15.33, 6p21-6p22 and 15q25.1 associated with lung cancer risk. Several other genetic regions including variants of CHEK2 (22q12), TP53BP1 (15q15) and RAD52 (12p13) have been demonstrated to influence lung cancer risk in candidate- or pathway-based analyses. To identify novel risk variants for lung cancer, we performed a meta-analysis of 16 GWASs, totaling 14 900 cases and 29 485 controls of European descent. Our data provided increased support for previously identified risk loci at 5p15 (P = 7.2 × 10-16), 6p21 (P = 2.3 × 10-14) and 15q25 (P = 2.2 × 10-63). Furthermore, we demonstrated histology-specific effects for 5p15, 6p21 and 12p13 loci but not for the 15q25 region. Subgroup analysis also identified a novel disease locus for squamous cell carcinoma at 9p21 (CDKN2A/p16INK4A/p14ARF/CDKN2B/p15INK4B/ANRIL; rs1333040, P = 3.0 × 10-7) which was replicated in a series of 5415 Han Chinese (P = 0.03; combined analysis, P = 2.3 × 10-8). This large analysis provides additional evidence for the role of inherited genetic susceptibility to lung cancer and insight into biological differences in the development of the different histological types of lung cancer.
UR - https://www.scopus.com/pages/publications/84868156549
U2 - 10.1093/hmg/dds334
DO - 10.1093/hmg/dds334
M3 - Article
C2 - 22899653
AN - SCOPUS:84868156549
SN - 0964-6906
VL - 21
SP - 4980
EP - 4995
JO - Human Molecular Genetics
JF - Human Molecular Genetics
IS - 22
M1 - dds334
ER -