Genome-wide interaction study of smoking behavior and non-small cell lung cancer risk in Caucasian population



Li, Yafang, Xiao, Xiangjun, Han, Younghun, Gorlova, Olga, Qian, David, Leighl, Natasha, Johansen, Jakob S, Barnett, Matt, Chen, Chu, Goodman, Gary
et al (show 66 more authors) (2018) Genome-wide interaction study of smoking behavior and non-small cell lung cancer risk in Caucasian population. CARCINOGENESIS, 39 (3). pp. 336-346.

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Abstract

Non-small cell lung cancer is the most common type of lung cancer. Both environmental and genetic risk factors contribute to lung carcinogenesis. We conducted a genome-wide interaction analysis between single nucleotide polymorphisms (SNPs) and smoking status (never- versus ever-smokers) in a European-descent population. We adopted a two-step analysis strategy in the discovery stage: we first conducted a case-only interaction analysis to assess the relationship between SNPs and smoking behavior using 13336 non-small cell lung cancer cases. Candidate SNPs with P-value <0.001 were further analyzed using a standard case-control interaction analysis including 13970 controls. The significant SNPs with P-value <3.5 × 10-5 (correcting for multiple tests) from the case-control analysis in the discovery stage were further validated using an independent replication dataset comprising 5377 controls and 3054 non-small cell lung cancer cases. We further stratified the analysis by histological subtypes. Two novel SNPs, rs6441286 and rs17723637, were identified for overall lung cancer risk. The interaction odds ratio and meta-analysis P-value for these two SNPs were 1.24 with 6.96 × 10-7 and 1.37 with 3.49 × 10-7, respectively. In addition, interaction of smoking with rs4751674 was identified in squamous cell lung carcinoma with an odds ratio of 0.58 and P-value of 8.12 × 10-7. This study is by far the largest genome-wide SNP-smoking interaction analysis reported for lung cancer. The three identified novel SNPs provide potential candidate biomarkers for lung cancer risk screening and intervention. The results from our study reinforce that gene-smoking interactions play important roles in the etiology of lung cancer and account for part of the missing heritability of this disease.

Item Type: Article
Uncontrolled Keywords: Humans, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Genetic Predisposition to Disease, Case-Control Studies, Smoking, Genotype, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Gene-Environment Interaction, Whites
Depositing User: Symplectic Admin
Date Deposited: 09 Aug 2018 08:44
Last Modified: 19 Jan 2023 01:29
DOI: 10.1093/carcin/bgx113
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3024786