Combined effects of cigarette smoking, gene polymorphisms and methylations of tumor suppressor genes on non small cell lung cancer: a hospital-based case-control study in China

Yongtang Jin,Shaoli Xue,Yong Hou,Chunye Zhang,Heyun Xu,Yingchun Xu,Yunming Kong

doi:10.1186/1471-2407-10-422

Yongtang Jin, Shaoli Xue + Show 5 more

Open Access

https://doi.org/10.1186/1471-2407-10-422

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Journal: BMC Cancer	Publication Date: Aug 12, 2010
Citations: 77	License type: cc-by

Affiliation: Zhejiang University, Anhui Medical University

Abstract

BackgroundCigarette smoking is the most established risk factor, and genetic variants and/or gene promoter methylations are also considered to play an essential role in development of lung cancer, but the pathogenesis of lung cancer is still unclear.MethodsWe collected the data of 150 cases and 150 age-matched and sex-matched controls on a Hospital-Based Case-Control Study in China. Face to face interviews were conducted using a standardized questionnaire. Gene polymorphism and methylation status were measured by RFLP-PCR and MSP, respectively. Logistic regressive model was used to estimate the odds ratios (OR) for different levels of exposure.ResultsAfter adjusted age and other potential confounding factors, smoking was still main risk factor and significantly increased 3.70-fold greater risk of NSCLC as compared with nonsmokers, and the ORs across increasing levels of pack years were 1, 3.54, 3.65 and 7.76, which the general dose-response trend was confirmed. Our striking findings were that the risk increased 5.16, 8.28 and 4.10-fold, respectively, for NSCLC with promoter hypermethylation of the p16, DAPK or RARβ gene in smokers with CYP1A1 variants, and the higher risk significantly increased in smokers with null GSTM1 and the OR was 17.84 for NSCLC with p16 promoter hypermethylation, 17.41 for DAPK, and 8.18 for RARβ in smokers with null GSTM1 compared with controls (all p < 0.01).ConclusionOur study suggests the strong combined effects of cigarette smoke, CYP1A1 and GSTM1 Polymorphisms, hypermethylations of p16, DAPK and RARβ promoters in NSCLC, implying complex pathogenesis of NSCLC should be given top priority in future research.

Highlights

Cigarette smoking is the most established risk factor, and genetic variants and/or gene promoter methylations are considered to play an essential role in development of lung cancer, but the pathogenesis of lung cancer is still unclear
Many studies have indicated that aberrant methylation of the promoter causes transcriptional silencing of some important suppressor genes, such as cell cycle gene p16, apoptosis gene DAPK, cell differentiation and proliferation gene RARb, DNA repair gene MGMT, and this has been implicated in the carcinogenic process in human lung cancer [4]
Those result suggested that GSTP1 and NQO1 variations increased the risk of MGMT methylation, and the possibility of p16 and RARb methylations was increased for XRCC1 and MPO gene polymorphisms, indicating the interactions between gene polymorphisms and aberrant methylation of tumor suppress genes

Summary

Introduction

Cigarette smoking is the most established risk factor, and genetic variants and/or gene promoter methylations are considered to play an essential role in development of lung cancer, but the pathogenesis of lung cancer is still unclear. Only a relative small study has examined the relationship between polymorphisms in XRCC1, GSTM1, GSTP1, NQO1, and MPO and aberrant methylation of p16, RARb and MGMT in lung cancer [6]. Those result suggested that GSTP1 and NQO1 variations increased the risk of MGMT methylation, and the possibility of p16 and RARb methylations was increased for XRCC1 and MPO gene polymorphisms, indicating the interactions between gene polymorphisms and aberrant methylation of tumor suppress genes

Methods

Results

Conclusion