细胞色素P4501A1基因多态性和谷胱甘肽硫转移酶基因缺失及烹调油烟暴露与非吸烟女性肺癌易感性的关系

目的 探讨细胞色素P4501 A1(CYP1A1)MspI位点多态性、谷胱甘肽硫转移酶(GSTM1)基因缺失及烹调油烟暴露与非吸烟女性肺癌易感性的关系.方法 2009年3一12月选择中南大学湘雅医院女性非吸烟的原发性肺癌患者及对照各160例,应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)及聚合酶链反应(PCR)技术分别检测CYP1A1 MspI多态性及GSTM1基因型,分析基因的多态性、分型及烹调油烟暴露与肺癌遗传易感性的关系.结果 肺癌组及对照组烹调油烟暴露的频率分别为51.9%(83例)及33.7%(54例),差异有统计学意义(x2=10.734,P＜0.01);肺癌组MspI位点突变的等位基因频率为44.4%(71例),高于对照组(36.9%,59例),差异无统计学意义(X2=3.731,P＞0.05);携带突变型或杂合型基因同时又有油烟暴露个体患肺癌的风险明显增高,OR(odds ratio)值分别为3.032(95%CI为1.291～7.124)和2.769(95%CI为1.341～5.552);肺癌组GSTM1缺失型的频率为58.1%(93例),与对照组(45.0%,72例)比较,差异有统计学意义(X2=0.518,P＜0.05),GSTM1缺失型的个体患肺癌的风险明显增高,OR值为1.697(95%CI为1.090～2.640);携带GSTM1缺失型且有烹调油烟暴露的个体肺癌的易感性明显增加,其OR值为3.617(95%CI为1.899～6.891);GSTM1缺失型与CYP1A1 MspI杂合型或突变型联合作用时,个体患肺癌的风险亦增高,OR值分别为1.966(95%CI为1.007～3.836)和2.402(95%CI为1.023～5.640),差异明显.结论 烹调油烟暴露是非吸烟女性肺癌的危险因素;CYP1A1 MspI基因多态性与烹调油烟联合作用可增加肺癌发病的风险;GSTM1基因缺失可能是非吸烟女性肺癌的遗传易感因素,其与烹调油烟暴露联合作用可明显增加肺癌发病的风险,且GSTM1基因缺失与CYP1A1基因多态性存在交互作用.

CYP1 A1 polymorphisms,lack of glutathione S-transferase M1 ( GSTM1 ),cooking oil fumes and lung cancer risk in non-smoking women

Objective To study the correlation of polymorphisms of CYP1 A1 MspI,GSTM1 null genotype,cooking oil fumes independently and in combination with the risk of non-smoking lung cancer in females.Methods One hundred and sixty female non-smoking patients with primary lung cancer and 160controls were enrolled from Xiangya Hospital of Central South University.PCR-RELP and PCR were used to detect the distribution of CYP1A1 MspI and GSTM1 genotypes respectively.The correlation of these genes and cooking oil fumes with the susceptibility to lung cancer was analyzed.Results There was a significant difference in the frequencies of cooking oil fumes exposure between cancer cases and controls( x2 = 10.734,P ＜ 0.01 );but there was no statistical difference in CYP1A1 MspI polymorphisms between the 2 groups (x2= 3.731 ,P ＞ 0.05 ).The combination of CYP1A1 polymorphisms and cooking oil fumes significantly increased the risk of lung cancer.The frequencies of GSTM1 null genotype was significantly different between cancer cases and controls ( x2 = 0.518,P ＜ 0.05).The risk of lung cancer was higher in those with the GSTM1 null genotype and the OR was 1.697 ( 95% CI 1.090 - 2.640).Individuals with both GSTM1 null genotype and exposure to cooking fumes had a higher risk of cancer than those with only one of them,the OR being 3.617(95% CI 1.899 -6.891 ).The combination of the two genes significantly increased the risk of lung cancer.Conclusions Cooking oil fumes exposure was a risk factor for non-smoking lung cancer in females.The combination of CYP1 A1 with cooking oil fume increased the risk of female lung cancer.GSTM1 null genotype was associated with risk of lung cancer in non-smoking females.The combination of GSTM1 null genotype and cooking oil fumes significantly increased the risk of female lung cancer.The combination of CYP1 A1 and GSTM1 significantly increased the risk of lung cancer.