Influence of common genetic variation on lung cancer risk: Meta-analysis of 14 900 cases and 29 485 controls

Maria N. Timofeeva; Rayjean J. Hung; Thorunn Rafnar; David C. Christiani; John K. Field; Heike Bickeböller; Angela Risch; James D. Mckay; Yufei Wang; Juncheng Dai; Valerie Gaborieau; John Mclaughlin; Darren Brenner; Steven A. Narod; Neil E. Caporaso; Demetrius Albanes; Michael Thun; Timothy Eisen; H. Erich Wichmann; Albert Rosenberger; Younghun Han; Wei Chen; Dakai Zhu; Margaret Spitz; Xifeng Wu; Mala Pande; Yang Zhao; David Zaridze; Neonilia Szeszenia-dabrowska; Jolanta Lissowska; Peter Rudnai; Eleonora Fabianova; Dana Mates; Vladimir Bencko; Lenka Foretova; Vladimir Janout; Hans E. Krokan; Maiken Elvestad Gabrielsen; Frank Skorpen; Lars Vatten; Inger NjØlstad; Chu Chen; Gary Goodman; Mark Lathrop; Simone Benhamou; TÕnu Vooder; Kristjan Välk; Mari Nelis; Andres Metspalu; Olaide Raji; Ying Chen; John Gosney; Triantafillos Liloglou; Thomas Muley; Hendrik Dienemann; Gudmar Thorleifsson; Hongbing Shen; Kari Stefansson; Paul Brennan; Christopher I. Amos; Richard Houlston; Maria Teresa Landi

doi:10.1093/hmg/dds334

Influence of common genetic variation on lung cancer risk: Meta-analysis of 14 900 cases and 29 485 controls

Maria N. Timofeeva, Rayjean J. Hung, Thorunn Rafnar, David C. Christiani, John K. Field, Heike Bickeböller, Angela Risch, James D. Mckay, Yufei Wang, Juncheng Dai, Valerie Gaborieau, John Mclaughlin, Darren Brenner, Steven A. Narod, Neil E. Caporaso, Demetrius Albanes, Michael Thun, Timothy Eisen, H. Erich Wichmann, Albert RosenbergerYounghun Han, Wei Chen, Dakai Zhu, Margaret Spitz, Xifeng Wu, Mala Pande, Yang Zhao, David Zaridze, Neonilia Szeszenia-dabrowska, Jolanta Lissowska, Peter Rudnai, Eleonora Fabianova, Dana Mates, Vladimir Bencko, Lenka Foretova, Vladimir Janout, Hans E. Krokan, Maiken Elvestad Gabrielsen, Frank Skorpen, Lars Vatten, Inger NjØlstad, Chu Chen, Gary Goodman, Mark Lathrop, Simone Benhamou, TÕnu Vooder, Kristjan Välk, Mari Nelis, Andres Metspalu, Olaide Raji, Ying Chen, John Gosney, Triantafillos Liloglou, Thomas Muley, Hendrik Dienemann, Gudmar Thorleifsson, Hongbing Shen, Kari Stefansson, Paul Brennan, Christopher I. Amos, Richard Houlston, Maria Teresa Landi

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Abstract

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/p16^INK4A/p14^ARF/CDKN2B/p15^INK4B/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.

Original language	English (US)
Article number	dds334
Pages (from-to)	4980-4995
Number of pages	16
Journal	Human molecular genetics
Volume	21
Issue number	22
DOIs	https://doi.org/10.1093/hmg/dds334
State	Published - Nov 2012

ASJC Scopus subject areas

Molecular Biology
Genetics
Genetics(clinical)

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Timofeeva, M. N., Hung, R. J., Rafnar, T., Christiani, D. C., Field, J. K., Bickeböller, H., Risch, A., Mckay, J. D., Wang, Y., Dai, J., Gaborieau, V., Mclaughlin, J., Brenner, D., Narod, S. A., Caporaso, N. E., Albanes, D., Thun, M., Eisen, T., Wichmann, H. E., ... Landi, M. T. (2012). Influence of common genetic variation on lung cancer risk: Meta-analysis of 14 900 cases and 29 485 controls. Human molecular genetics, 21(22), 4980-4995. Article dds334. https://doi.org/10.1093/hmg/dds334

Timofeeva, MN, Hung, RJ, Rafnar, T, Christiani, DC, Field, JK, Bickeböller, H, Risch, A, Mckay, JD, Wang, Y, Dai, J, Gaborieau, V, Mclaughlin, J, Brenner, D, Narod, SA, Caporaso, NE, Albanes, D, Thun, M, Eisen, T, Wichmann, HE, Rosenberger, A, Han, Y, Chen, W, Zhu, D, Spitz, M, Wu, X, Pande, M, Zhao, Y, Zaridze, D, Szeszenia-dabrowska, N, Lissowska, J, Rudnai, P, Fabianova, E, Mates, D, Bencko, V, Foretova, L, Janout, V, Krokan, HE, Gabrielsen, ME, Skorpen, F, Vatten, L, NjØlstad, I, Chen, C, Goodman, G, Lathrop, M, Benhamou, S, Vooder, TÕ, Välk, K, Nelis, M, Metspalu, A, Raji, O, Chen, Y, Gosney, J, Liloglou, T, Muley, T, Dienemann, H, Thorleifsson, G, Shen, H, Stefansson, K, Brennan, P, Amos, CI, Houlston, R & Landi, MT 2012, 'Influence of common genetic variation on lung cancer risk: Meta-analysis of 14 900 cases and 29 485 controls', Human molecular genetics, vol. 21, no. 22, dds334, pp. 4980-4995. https://doi.org/10.1093/hmg/dds334

@article{f64d927acf09497c953c05353baf9862,

title = "Influence of common genetic variation on lung cancer risk: Meta-analysis of 14 900 cases and 29 485 controls",

abstract = "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.",

author = "Timofeeva, {Maria N.} and Hung, {Rayjean J.} and Thorunn Rafnar and Christiani, {David C.} and Field, {John K.} and Heike Bickeb{\"o}ller and Angela Risch and Mckay, {James D.} and Yufei Wang and Juncheng Dai and Valerie Gaborieau and John Mclaughlin and Darren Brenner and Narod, {Steven A.} and Caporaso, {Neil E.} and Demetrius Albanes and Michael Thun and Timothy Eisen and Wichmann, {H. Erich} and Albert Rosenberger and Younghun Han and Wei Chen and Dakai Zhu and Margaret Spitz and Xifeng Wu and Mala Pande and Yang Zhao and David Zaridze and Neonilia Szeszenia-dabrowska and Jolanta Lissowska and Peter Rudnai and Eleonora Fabianova and Dana Mates and Vladimir Bencko and Lenka Foretova and Vladimir Janout and Krokan, {Hans E.} and Gabrielsen, {Maiken Elvestad} and Frank Skorpen and Lars Vatten and Inger Nj{\O}lstad and Chu Chen and Gary Goodman and Mark Lathrop and Simone Benhamou and T{\~O}nu Vooder and Kristjan V{\"a}lk and Mari Nelis and Andres Metspalu and Olaide Raji and Ying Chen and John Gosney and Triantafillos Liloglou and Thomas Muley and Hendrik Dienemann and Gudmar Thorleifsson and Hongbing Shen and Kari Stefansson and Paul Brennan and Amos, {Christopher I.} and Richard Houlston and Landi, {Maria Teresa}",

note = "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/Troms{\o} and CARET genome-wide studies was provided by Institut National du Cancer, France. Support for the HUNT2/Troms{\o} 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{\textquoteright}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).",

year = "2012",

month = nov,

doi = "10.1093/hmg/dds334",

language = "English (US)",

volume = "21",

pages = "4980--4995",

journal = "Human molecular genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "22",

}

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.

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DO - 10.1093/hmg/dds334

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JF - Human molecular genetics

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M1 - dds334

ER -

Influence of common genetic variation on lung cancer risk: Meta-analysis of 14 900 cases and 29 485 controls

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