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

Authors	TIMOFEEVA Maria N. HUNG Rayjean J. RAFNAR Thorunn CHRISTIANI David C. FIELD John K. BICKEBOELLER 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 FABIANOVÁ Eleonora MATES Dana BENCKO Vladimir FORETOVÁ 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 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
Year of publication	2012
Type	Article in Periodical
Magazine / Source	Human molecular genetics
MU Faculty or unit	Faculty of Medicine
Citation
Doi	http://dx.doi.org/10.1093/hmg/dds334
Field	Oncology and hematology
Keywords	GENOME-WIDE ASSOCIATION; CORONARY-ARTERY-DISEASE; DNA DOUBLE-STRAND; SUSCEPTIBILITY LOCI; LARGE-SCALE; JAPANESE POPULATION; GENOTYPE IMPUTATION; NICOTINE DEPENDENCE; IN-VIVO; VARIANTS
Description	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.