细胞色素P450 2E1（CYP2E1）和谷胱甘肽S-转移酶M1（GSTM1）基因多态性、环境因素与肺癌易感性
CYP2E1 and GSTM1 gene polymorphisms, environmental factors, and the susceptibility to lung cancer.
作者信息
He Qingfang, Wang Lixin, Zhang Jie, Lu Feng, Gong Weiwei, Pan Jin, Zhong Jieming, Hu Ruying, Yu Min
机构信息
Zhejiang Provincial Center for Disease Prevention and Control, Hangzhou, China.
出版信息
J Clin Lab Anal. 2018 Jul;32(6):e22403. doi: 10.1002/jcla.22403. Epub 2018 Mar 31.
OBJECTIVE
To investigate the relationships between the CYP2E1 RsaI polymorphism, GSTM1 polymorphism, and the susceptibility to lung cancer, along with the interactions between environmental factors and these genes.
METHODS
A case-control study was carried out to explore the independent effect of gene polymorphisms on risk of lung cancer, and the combined effects of gene loci. The stratification analysis of age, sex, smoking, and drinking combined with positive loci was also analyzed, and any interaction was identified.
RESULTS
The logistic regression analysis showed that there were statistical relationships between the CYP2E1 RsaI TT genotype and lung cancer, GSTM1 (-) and lung cancer. The combined effect's analysis of these 2 loci showed that, with an increase in the number of risk alleles, the risk of lung cancer also increased (supposing 0 risk allele as the reference group). Subjects carrying 3 risk alleles had the highest risk of developing lung cancer with an adjusted OR = 10.38 (95% CI 2.10-51.35). Stratified analysis showed that, in women, nonsmoking subjects, or nondrinking subjects, the combined effects could increase the risk of lung cancer; no heterogeneity was found between these layers except sex. The interaction analysis showed that, supposing the male, GSTM1 (+) genotype as the reference, the female, GSTM1 (-) genotype had a significantly increased risk of lung cancer (OR = 2.17 [1.01-4.70]); when the non-smoking, GSTM1 (+) genotype subjects was the reference group, smoking, GSTM1 (+) genotype subjects and smoking, GSTM1 (-) genotype subjects had significantly higher risk of lung cancer (OR = 2.00 [1.01-3.96], OR = 2.89 [1.28-6.54]).
CONCLUSION
CYP2E1 RsaI TT genotype was a protective factor against the development of lung cancer, while GSTM1 (-) genotype was a risk factor for lung cancer. Increases in the number of the risk alleles also increased lung cancer risk. GSTM1 (-) genotype, sex, and smoking status might interact in the incidence of lung cancer.
目的
探讨细胞色素P450 2E1（CYP2E1）RsaI基因多态性、谷胱甘肽S转移酶M1（GSTM1）基因多态性与肺癌易感性的关系，以及环境因素与这些基因之间的相互作用。
方法
开展一项病例对照研究，以探讨基因多态性对肺癌风险的独立影响以及基因位点的联合效应。还对年龄、性别、吸烟和饮酒与阳性位点进行分层分析，并确定是否存在相互作用。
结果
逻辑回归分析显示，CYP2E1 RsaI TT基因型与肺癌、GSTM1（-）与肺癌之间存在统计学关联。对这两个位点的联合效应分析表明，随着风险等位基因数量的增加，肺癌风险也增加（以0个风险等位基因为参照组）。携带3个风险等位基因的受试者患肺癌的风险最高，校正后的比值比（OR）=10.38（95%置信区间2.10 - 51.35）。分层分析表明，在女性、不吸烟受试者或不饮酒受试者中，联合效应会增加肺癌风险；除性别外，这些分层之间未发现异质性。相互作用分析表明，以男性、GSTM1（+）基因型为参照，女性、GSTM1（-）基因型患肺癌的风险显著增加（OR = 2.17 [1.01 - 4.70]）；以不吸烟、GSTM1（+）基因型受试者为参照组时，吸烟、GSTM1（+）基因型受试者和吸烟、GSTM1（-）基因型受试者患肺癌的风险显著更高（OR = 2.00 [1.01 - 3.96]，OR = 2.89 [1.28 - 6.54]）。
结论
CYP2E1 RsaI TT基因型是肺癌发生的保护因素，而GSTM1（-）基因型是肺癌的风险因素。风险等位基因数量的增加也会增加肺癌风险。GSTM1（-）基因型、性别和吸烟状况可能在肺癌发病中相互作用。
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