From IARC-Lyon: Influence of Common Genetic Variation on Lung Cancer Risk: Meta-Analysis of 14,900 Cases and 29,485 Controls

http://www.ncbi.nlm.nih.gov/pubmed/22899653

Hum Mol Genet. 2012 Aug 16. [Epub ahead of print]

Influence of Common Genetic Variation on Lung Cancer Risk: Meta-Analysis of 14,900 Cases and 29,485 Controls.

Timofeeva MN, Hung RJ, Rafnar T, Christiani DC, Field JK, Bickeboller H, Risch A, McKay JD, Wang Y, Dai J, Gaborieau V, McLaughlin J, Brenner D, Narod S,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 T, 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; for TRICL Research Team.

Source

International Agency for Research on Cancer, Lyon, 69008, France.

Abstract

Recent genome-wide association studies (GWAS) have identified common genetic variants at 5p15.33, 6p21-22 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 GWAS, totaling 14,900 cases and 29,485 controls of European descent. Our data provided increased support for previously identified risk loci at 5p15 (P=7.2x10(-16)), 6p21 (P=2.3x10(-14)) and 15q25 (P=2.2x10(-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=3.0x10(-7)) which was replicated in a series of 5,415 Han Chinese (P=0.03; combined analysis P=2.3x10(-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.