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.
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.
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DOI：
10.1186/1471-2407-10-422
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发表时间：
2010-08-12
期刊：
影响因子：
3.8
通讯作者：
Xue S
中科院分区：
文献类型：
--
作者：
Jin Y;Xu H;Zhang C;Kong Y;Hou Y;Xu Y;Xue S
吸烟是最确定的危险因素，遗传变异和/或基因启动子甲基化也被认为在肺癌的发生中起重要作用，但肺癌的发病机制仍不清楚。我们收集了150例病例和150名年龄和性别匹配的对照的数据，在中国进行了基于医院的病例对照研究。采用标准化问卷进行面对面访谈。采用RFLP-PCR检测基因多态性，MSP检测基因甲基化状态。采用Logistic回归模型估计不同暴露水平的比值比（OR）。在调整年龄和其他潜在混杂因素后，吸烟仍是主要危险因素，与不吸烟者相比，吸烟者发生NSCLC的风险显著增加3.70倍，增加包年水平的OR分别为1、3.54、3.65和7.76，证实了总体剂量反应趋势。我们的惊人发现是，在携带CYP 1A 1变异体的吸烟者中，p16、DAPK或RARβ基因启动子高甲基化的NSCLC风险分别增加5.16、8.28和4.10倍，在GSTM 1缺失的吸烟者中，风险显著增加，NSCLC伴p16启动子高甲基化的OR为17.84，DAPK为17.41，吸烟者GSTM 1基因缺失者RARβ表达为8.18，与对照组比较差异均有显著性（P < 0.01）。本研究提示吸烟、CYP 1A 1和GSTM 1基因多态性、p16、DAPK和RARβ基因启动子高甲基化在NSCLC发病中具有重要的联合作用，提示NSCLC的发病机制是复杂的，在未来的研究中应优先考虑。
Cigarette 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. We 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. After 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). Our 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.
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