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; Ying Chen; Triantafillos Liloglou

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, Ying Chen, Triantafillos Liloglou

Research output: Contribution to journal › Article (journal) › peer-review

191 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/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
Pages (from-to)	4980-95
Number of pages	16
Journal	Human Molecular Genetics
Volume	21
Issue number	22
DOIs	https://doi.org/10.1093/hmg/dds334
Publication status	Published - 15 Nov 2012

Keywords

Asian People/genetics
Case-Control Studies
Genetic Variation
Genome-Wide Association Study
Humans
Lung Neoplasms/epidemiology
Polymorphism, Single Nucleotide
Risk
White People/genetics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/hmg/dds334

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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., ... Liloglou, 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), 4980-95. https://doi.org/10.1093/hmg/dds334

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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/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.",

keywords = "Asian People/genetics, Case-Control Studies, Genetic Variation, Genome-Wide Association Study, Humans, Lung Neoplasms/epidemiology, Polymorphism, Single Nucleotide, Risk, White People/genetics",

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 H-Erich Wichmann 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 Ying Chen and Triantafillos Liloglou",

year = "2012",

month = nov,

day = "15",

doi = "10.1093/hmg/dds334",

language = "English",

volume = "21",

pages = "4980--95",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "22",

}

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, H-E, 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, T, Välk, K, Nelis, M, Chen, Y & Liloglou, T 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, pp. 4980-95. https://doi.org/10.1093/hmg/dds334

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 - Chen, Ying

AU - Liloglou, Triantafillos

PY - 2012/11/15

Y1 - 2012/11/15

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/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.

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/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.

KW - Asian People/genetics

KW - Case-Control Studies

KW - Genetic Variation

KW - Genome-Wide Association Study

KW - Humans

KW - Lung Neoplasms/epidemiology

KW - Polymorphism, Single Nucleotide

KW - Risk

KW - White People/genetics

U2 - 10.1093/hmg/dds334

DO - 10.1093/hmg/dds334

M3 - Article (journal)

C2 - 22899653

SN - 0964-6906

VL - 21

SP - 4980

EP - 4995

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 22

ER -

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

Abstract

Keywords

UN SDGs

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