Affiliations: [a] Environmental Epigenetics Laboratory, Department of Environmental Medicine, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China | [b] Department of Cardiothoracic Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
Correspondence:
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Corresponding author: Yong-Tang Jin, Yuhangtang Road No. 866, Environmental Epigenetics Laboratory, Department of Environmental Medicine, School of Medicine, Zhejiang University, Hangzhou 310058, Zhejiang, China. Tel.: +86 571 88206897; Fax: +86 571 88206897; E-mail: jinedu@zju.edu.cn.
Abstract: Purpose:The aim of this study was to investigate the methylation status of three cell adhesion-related genes including CDH1, TSLC1 and TIMP3 in non-small cell lung cancer and explore its association with clinicopathologic features and various environmental risk factors. Methods:We detected the aberrant methylation presence of these genes by methylation-specific polymerase chain reaction and analyzed the potential correlations with multivariate logistic regression model as well as stepwise logistic regression. Results:For CDH1, promoter methylation was less frequent in adenosquamous carcinomas than adenocarcinomas (OR=0.35, 95%CI=0.13–0.96); pickled food increased the methylation frequency (OR=2.23, 95%CI=1.09–4.54) while light smoking and fruit intake decreased that (OR=0.43, 95%CI=0.19–0.97; OR=0.37, 95%CI=0.15–0.95). For TSLC1, males and toxin exposure increased methylation frequency (OR=6.25, 95%CI=1.05–37.13; OR=2.42, 95%CI=1.01–5.77) while light smoking and radiation exposure decreased that (OR=0.14, 95%CI=0.03–0.60; OR=0.17, 95%CI=0.04–0.87). For TIMP3, males showed lower methylation frequency than females (OR=0.18, 95%CI=0.04–0.88) while central lung cancer, heavy smoking and radiation exposure presented higher aberrant DNA methylation status (OR=2.19, 95%CI=1.07–4.52; OR=6.99, 95%CI=1.32–37.14; OR=2.30, 95%CI=1.04–5.08). Conclusions:Aberrant promoter methylation of cell adhesion-related tumor suppressor genes in lung cancer displayed varieties of gene-specific correlations with clinicopathologic features and various environmental risk factors.
Keywords: CDH1, TSLC1, TIMP3, methylation, non-small cell lung cancer
