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 & 42 others 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

Research output: Contribution to journalArticle

122 Citations (Scopus)

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.

Original languageEnglish
Article numberdds334
Pages (from-to)4980-4995
Number of pages16
JournalHuman Molecular Genetics
Volume21
Issue number22
DOIs
Publication statusPublished - Nov 2012

Fingerprint

Meta-Analysis
Lung Neoplasms
Genome-Wide Association Study
Tumor Suppressor Protein p14ARF
Genetic Predisposition to Disease
Squamous Cell Carcinoma
Histology

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

Cite this

Timofeeva, M. N., Hung, R. J., Rafnar, T., Christiani, D. C., Field, J. K., Bickeböller, H., ... 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. [dds334]. https://doi.org/10.1093/hmg/dds334

Influence of common genetic variation on lung cancer risk : Meta-analysis of 14 900 cases and 29 485 controls. / Timofeeva, Maria N.; Hung, Rayjean J.; Rafnar, Thorunn; Christiani, David C.; Field, John K.; Bickeböller, Heike; Risch, Angela; Mckay, James D.; Wang, Yufei; Dai, Juncheng; Gaborieau, Valerie; Mclaughlin, John; Brenner, Darren; Narod, Steven A.; Caporaso, Neil E.; Albanes, Demetrius; Thun, Michael; Eisen, Timothy; Wichmann, H. Erich; Rosenberger, Albert; Han, Younghun; Chen, Wei; Zhu, Dakai; Spitz, Margaret; Wu, Xifeng; Pande, Mala; Zhao, Yang; Zaridze, David; Szeszenia-dabrowska, Neonilia; Lissowska, Jolanta; Rudnai, Peter; Fabianova, Eleonora; Mates, Dana; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Krokan, Hans E.; Gabrielsen, Maiken Elvestad; Skorpen, Frank; Vatten, Lars; NjØlstad, Inger; Chen, Chu; Goodman, Gary; Lathrop, Mark; Benhamou, Simone; Vooder, TÕnu; Välk, Kristjan; Nelis, Mari; Metspalu, Andres; Raji, Olaide; Chen, Ying; Gosney, John; Liloglou, Triantafillos; Muley, Thomas; Dienemann, Hendrik; Thorleifsson, Gudmar; Shen, Hongbing; Stefansson, Kari; Brennan, Paul; Amos, Christopher I.; Houlston, Richard; Landi, Maria Teresa.

In: Human Molecular Genetics, Vol. 21, No. 22, dds334, 11.2012, p. 4980-4995.

Research output: Contribution to journalArticle

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
Timofeeva MN, Hung RJ, Rafnar T, Christiani DC, Field JK, Bickeböller H et al. Influence of common genetic variation on lung cancer risk: Meta-analysis of 14 900 cases and 29 485 controls. Human Molecular Genetics. 2012 Nov;21(22):4980-4995. dds334. https://doi.org/10.1093/hmg/dds334
Timofeeva, Maria N. ; Hung, Rayjean J. ; Rafnar, Thorunn ; Christiani, David C. ; Field, John K. ; Bickeböller, Heike ; Risch, Angela ; Mckay, James D. ; Wang, Yufei ; Dai, Juncheng ; Gaborieau, Valerie ; Mclaughlin, John ; Brenner, Darren ; Narod, Steven A. ; Caporaso, Neil E. ; Albanes, Demetrius ; Thun, Michael ; Eisen, Timothy ; Wichmann, H. Erich ; Rosenberger, Albert ; Han, Younghun ; Chen, Wei ; Zhu, Dakai ; Spitz, Margaret ; Wu, Xifeng ; Pande, Mala ; Zhao, Yang ; Zaridze, David ; Szeszenia-dabrowska, Neonilia ; Lissowska, Jolanta ; Rudnai, Peter ; Fabianova, Eleonora ; Mates, Dana ; Bencko, Vladimir ; Foretova, Lenka ; Janout, Vladimir ; Krokan, Hans E. ; Gabrielsen, Maiken Elvestad ; Skorpen, Frank ; Vatten, Lars ; NjØlstad, Inger ; Chen, Chu ; Goodman, Gary ; Lathrop, Mark ; Benhamou, Simone ; Vooder, TÕnu ; Välk, Kristjan ; Nelis, Mari ; Metspalu, Andres ; Raji, Olaide ; Chen, Ying ; Gosney, John ; Liloglou, Triantafillos ; Muley, Thomas ; Dienemann, Hendrik ; Thorleifsson, Gudmar ; Shen, Hongbing ; Stefansson, Kari ; Brennan, Paul ; Amos, Christopher I. ; Houlston, Richard ; Landi, Maria Teresa. / Influence of common genetic variation on lung cancer risk : Meta-analysis of 14 900 cases and 29 485 controls. In: Human Molecular Genetics. 2012 ; Vol. 21, No. 22. pp. 4980-4995.
@article{8751480235ce44478adb78734728d1e4,
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}",
year = "2012",
month = "11",
doi = "10.1093/hmg/dds334",
language = "English",
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

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 - http://www.scopus.com/inward/record.url?scp=84868156549&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84868156549&partnerID=8YFLogxK

U2 - 10.1093/hmg/dds334

DO - 10.1093/hmg/dds334

M3 - Article

VL - 21

SP - 4980

EP - 4995

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 22

M1 - dds334

ER -