CYP2E1 and GSTM1 gene polymorphisms, environmental factors, and the susceptibility to lung cancer
Qingfang He1, Lixin Wang1, Jie Zhang1
1Zhejiang Provincial Center for Disease Prevention and Control, Hangzhou, China.
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.
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