吸烟及烟碱型乙酰胆碱受体亚单位α5基因rs17486278位点多态性对肺癌的交互作用

Interaction between smoking and nicotine acetylcholine receptor subunits alpha 5 gene rs17486278 polymorphisms on lung cancer

目的 探讨在中国男性人群中吸烟、烟碱型乙酰胆碱受体亚单位α5（CHRNA5）基因多态性与肺癌的关联及其交互作用.方法 采用成组病例对照研究设计,收集男性原发性肺癌病例204例,正常健康对照者821例.采用结构式问卷调查社会人口学特征、吸烟行为及健康状况等,采集静脉血检测CHRNA5 SNP位点rs17486278的多态性.应用多因素logistic回归模型分析吸烟、CHRNA5的基因多态性与肺癌的关系及其交互作用.结果 控制潜在混杂因素后,每天吸烟量＞15支者发生肺癌的风险高于不吸烟者（OR=3.49,95％CI：2.29～ 5.32）,未发现CHRNA5上的rs17486278多态性与肺癌有统计学关联.进一步交互作用分析显示,每天吸烟量1～15支并携带rs17486278纯合变异基因型（CC）者对肺癌的发生存在正交互作用（OR=16.13,95％CI：1.27～205.33）.根据rs17486278多态性和吸烟行为进行分层分析,与不吸烟并携带rs17486278野生基因型（AA）者相比,每天吸烟量1～15支并携带纯合变异基因型（CC）者、每天吸烟量＞15支并携带野生基因型（AA）者和每天吸烟量＞15支并携带杂合变异基因型（AC）者发生肺癌风险增高,OR直分别为8.14（95％CI：1.17 ～ 56.56）、3.84（95％CI：1.30～ 11.40）和5.32（95％CI：1.78 ～ 15.93）.结论 在中国男性人群中CHRNA5的基因多态性与吸烟行为对肺癌的发生存在正交互作用.

Objective To investigate the association and interaction between smoking and the nicotine acetylcholine receptor subunits alpha 5 （CHRNA5） gene polymorphisms on lung cancer in Chinese men.Methods A case-control study was employed with a total of 204 male lung cancer patients and 821 healthy control subjects enrolled in the study.All the subjects were interviewed under a structured questionnaire with the contents on socio-demographic status and smoking behavior.Venous blood samples were collected to measure single nucleotide polymorphism of rs17486278 in CHRNA5.A series of multivariate logistic regression models were performed to assess the association and interaction between smoking and the CHRNA5 gene polymorphisms on lung cancer.Results After controlling for potential confounding factors,data from the multivariate logistic regression analysis showed that individuals with smoking 〉 15 cigarettes per day would significantly increase the risk of lung cancer when compared to the non-smokers （OR =3.49,95%CI：2.29-5.32）.However,no associations between CHRNA5 rs17486278 polymorphisms and lung cancer were found.Furthermore,those who smoked 1-15 cigarettes per day had a positive interactive effect between rs17486278 CC genotype and lung cancer （OR=16.13,95% CI：1.27-205.33）.Results from further stratified analysis on smoking behaviors and rs17486278 genotypes indicated that when compared with non-smokers on rs 17486278 AA genotype,those individuals who smoked 1-15 cigarettes per day with rs17486278 CC genotype,individuals smoking 〉 15 cigarettes per day with AA genotype and individuals smoking 〉 15 cigarettes per day with AC genotype,all had a higher risk of developing lung cancer,with their OR value as 8.14 （95% CI：1.17-56.56）,3.84 （95% CI：1.30-11.40） and 5.32（95% CI：1.78-15.93）,respectively.Conclusion There was an interaction between smoking and CHRNA5 gene polymorphism on lung cancer.