PuSH - Publication Server of Helmholtz Zentrum München

Wang, Y.* ; Gorlova, O.Y.* ; Gorlov, I.P.* ; Zhu, M.* ; Dai, J.* ; Albanes, D.* ; Lam, S.* ; Tardón, A.* ; Chen, C.* ; Goodman, G.E.* ; Bojesen, S.E.* ; Landi, M.T.* ; Johansson, M.* ; Risch, A.* ; Wichmann, H.-E. ; Bickeböller, H.* ; Christiani, D.C.* ; Rennert, G.* ; Arnold, S.M.* ; Brennan, P.* ; Field, J.K.* ; Shete, S.* ; Le Marchand, L.* ; Melander, O.* ; Brunnström, H.* ; Liu, G.* ; Hung, R.J.* ; Andrew, A.S.* ; Kiemeney, L.A.* ; Zienolddiny, S.* ; Grankvist, K.* ; Caporaso, N.E.* ; Woll, P.J.* ; Lazarus, P.* ; Schabath, M.B.* ; Aldrich, M.C.* ; Stevens, V.L.* ; Ma, H.* ; Jin, G.* ; Hu, Z.* ; Amos, C.I.* ; Shen, H.*

Association analysis of driver-gene related genetic variants identified novel lung cancer susceptibility loci with 20,871 lung cancer cases and 15,971 controls.

Cancer Epidemiol. Biomarkers Prev. 29, 1423-1429 (2020)
Publ. Version/Full Text Postprint DOI PMC
Open Access Green
Background: A substantial proportion of cancer driver genes (CDG) are also cancer predisposition genes. However, the associations between genetic variants in lung CDGs and the susceptibility to lung cancer have rarely been investigated.Methods: We selected expression-related single-nucleotide polymorphisms (eSNP) and nonsynonymous variants of lung CDGs, and tested their associations with lung cancer risk in two large-scale genome-wide association studies (20,871 cases and 15,971 controls of European descent). Conditional and joint association analysis was performed to identify independent risk variants. The associations of independent risk variants with somatic alterations in lung CDGs or recurrently altered pathways were investigated using data from The Cancer Genome Atlas (TCGA) project.Results: We identified seven independent SNPs in five lung CDGs that were consistently associated with lung cancer risk in discovery (P < 0.001) and validation (P < 0.05) stages. Among these loci, rs78062588 in TPM3 (1q21.3) was a new lung cancer susceptibility locus (OR = 0.86, P = 1.65 x 10(-6)). Subgroup analysis by histologic types further identified nine lung CDGs. Analysis of somatic alterations found that in lung adenocarcinomas, rs78062588[C] allele (TPM3 in 1q21.3) was associated with elevated somatic copy number of TPM3 (OR = 1.16, P = 0.02). In lung adenocarcinomas, rs1611182 (HLA-A in 6p22.1) was associated with truncation mutations of the transcriptional misregulation in cancer pathway (OR = 0.66, P = 1.76 x 10(-3)).Conclusions: Genetic variants can regulate functions of lung CDGs and influence lung cancer susceptibility.Impact: Our findings might help unravel biological mechanisms underlying lung cancer susceptibility.
Altmetric
Additional Metrics?
[➜Log in]
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Expression; Irf6; Fusion
ISSN (print) / ISBN 1055-9965
e-ISSN 1538-7755
Journal Cancer Epidemiology, Biomarkers & Prevention
Quellenangaben Volume: 29, Issue: 7, Pages: 1423-1429 Article Number: , Supplement: ,
Publisher American Association for Cancer Research (AACR)
Publishing Place 615 Chestnut St, 17th Floor, Philadelphia, Pa 19106-4404 Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)