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Association analyses identify multiple new lung cancer susceptibility loci and their interactions with smoking in the Chinese population. Nat Genet 2012 Jul 15;44(8):895-9

Date

07/17/2012

Pubmed ID

22797725

Pubmed Central ID

PMC6628171

DOI

10.1038/ng.2351

Scopus ID

2-s2.0-84864411351 (requires institutional sign-in at Scopus site)   125 Citations

Abstract

To find additional susceptibility loci for lung cancer, we tested promising associations from our previous genome-wide association study (GWAS) of lung cancer in the Chinese population in an extended validation sample size of 7,436 individuals with lung cancer (cases) and 7,483 controls. We found genome-wide significant (P < 5.0 × 10(-8)) evidence for three additional lung cancer susceptibility loci at 10p14 (rs1663689, close to GATA3, P = 2.84 × 10(-10)), 5q32 (rs2895680 in PPP2R2B-STK32A-DPYSL3, P = 6.60 × 10(-9)) and 20q13.2 (rs4809957 in CYP24A1, P = 1.20 × 10(-8)). We also found consistent associations for rs247008 at 5q31.1 (IL3-CSF2-P4HA2, P = 7.68 × 10(-8)) and rs9439519 at 1p36.32 (AJAP1-NPHP4, P = 3.65 × 10(-6)). Four of these loci showed evidence for interactions with smoking dose (P = 1.72 × 10(-10), P = 5.07 × 10(-3), P = 6.77 × 10(-3) and P = 4.49 × 10(-2) for rs2895680, rs4809957, rs247008 and rs9439519, respectively). These results advance our understanding of lung cancer susceptibility and highlight potential pathways that integrate genetic variants and smoking in the development of lung cancer.

Author List

Dong J, Hu Z, Wu C, Guo H, Zhou B, Lv J, Lu D, Chen K, Shi Y, Chu M, Wang C, Zhang R, Dai J, Jiang Y, Cao S, Qin Z, Yu D, Ma H, Jin G, Gong J, Sun C, Zhao X, Yin Z, Yang L, Li Z, Deng Q, Wang J, Wu W, Zheng H, Zhou G, Chen H, Guan P, Peng Z, Chen Y, Shu Y, Xu L, Liu X, Liu L, Xu P, Han B, Bai C, Zhao Y, Zhang H, Yan Y, Amos CI, Chen F, Tan W, Jin L, Wu T, Lin D, Shen H

Author

Jing Dong PhD Assistant Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Case-Control Studies
China
GATA3 Transcription Factor
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Lung Neoplasms
Muscle Proteins
Nerve Tissue Proteins
Polymorphism, Single Nucleotide
Protein Phosphatase 2
Smoking
Steroid Hydroxylases
Vitamin D3 24-Hydroxylase