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

About this Publication
Title
Influence of common genetic variation on lung cancer risk: meta-analysis of 14 900 cases and 29 485 controls.
Pubmed ID
22899653 (View this publication on the PubMed website)
Publication
Hum. Mol. Genet. 2012 Nov; Volume 21 (Issue 22): Pages 4980-95
Authors
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, ...show more 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, Transdisciplinary Research in Cancer of the Lung (TRICL) Research Team
Affiliations
  • International Agency for Research on Cancer, Lyon, France.
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.

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