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.; Bickeboeller, Heike; Risch, Angela; McKay, James D.; Wang, Y.; Dai, Juncheng; Gaborieau, Valerie; McLaughlin, John R.; Brenner, Darren; Narod, Steven A.; Caporaso, Neil E.; Albanes, Demetrius; Thun, Michael; Eisen, Timothy; Wichmann, Heinz-Erich; Rosenberger, Albert; Han, Younghun; Chen, Wei; Zhu, D.; Spitz, Margaret R.; Wu, X.; 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; Njolstad, Inger; Chen, Chu; Goodman, Gary; Lathrop, Mark; Benhamou, Simone; Vooder, Tonu; Vaelk, Kristjan; Nelis, Mari; Metspalu, Andres; Raji, Olaide Y.; Chen, Ying; Gosney, John; Liloglou, Triantafillos; Muley, Thomas; Dienemann, Hendrik; Thorleifsson, Gudmar; Shen, Hongbing; Stefansson, Kari; Brennan, P. C.; Amos, Christopher I.; Houlston, Richard S.; Landi, Maria Teresa

doi:10.1093/hmg/dds334

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

ISSN

1460-2083

0964-6906

Date Issued

2012

Author(s)

Timofeeva, Maria N.

Hung, Rayjean J.

Rafnar, Thorunn

Christiani, David C.

Field, John K.

Bickeboeller, Heike

Risch, Angela

McKay, James D.

Wang, Y.

Dai, Juncheng

Gaborieau, Valerie

McLaughlin, John R.

Brenner, Darren

Narod, Steven A.

Caporaso, Neil E.

Albanes, Demetrius

Thun, Michael

Eisen, Timothy

Wichmann, Heinz-Erich

Rosenberger, Albert

Han, Younghun

Chen, Wei

Zhu, D.

Spitz, Margaret R.

Wu, X.

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

Njolstad, Inger

Chen, Chu

Goodman, Gary

Lathrop, Mark

Benhamou, Simone

Vooder, Tonu

Vaelk, Kristjan

Nelis, Mari

Metspalu, Andres

Raji, Olaide Y.

Chen, Ying

Gosney, John

Liloglou, Triantafillos

Muley, Thomas

Dienemann, Hendrik

Thorleifsson, Gudmar

Shen, Hongbing

Stefansson, Kari

Brennan, P. C.

Amos, Christopher I.

Houlston, Richard S.

Landi, Maria Teresa

DOI

10.1093/hmg/dds334

Abstract

Recent genome-wide association studies (GWASs) have identified common genetic variants at 5p15.33, 6p216p22 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.