Genetic polymorphisms in CYP1A1, GSTM1, GSTP1 and GSTT1metabolic genes and risk of lung cancer in Asturias

Abstract

Background: Metabolic genes have been associated with the function of metabolizing and detoxifying environmental carcinogens. Polymorphisms present in these genes could lead to changes in their metabolizing and detoxifying ability and thus may contribute to individual susceptibility to different types of cancer. We investigated if the individual and/or combined modifying effects of theCYP1A1 MspIT6235C,GSTM1 present/null,GSTT1 present/nullandGSTP1 Ile105Valpolymorphisms are related to the risk of developing lung cancer in relation to tobacco consumption and occupation in Asturias, Northern Spain.Methods: A hospital-based case–control study (CAPUA Study) was designed including 789 lung cancer patients and 789 control subjects matched in ethnicity, age, sex, and hospital. Genotypes were determined by PCR or PCR-RFLP. Individual and combination effects were analysed using an unconditional logistic regression adjusting for age, pack-years, family history of any cancer and occupation.Results: No statistically significant main effects were observed for the carcinogen metabolism genes in relation to lung cancer risk. In addition, the analysis did not reveal any significant gene-gene, gene-tobacco smoking or gene-occupational exposure interactions relative to lung cancer susceptibility. Lastly, no significant gene-gene combination effects were observed.Conclusions: These results suggest that genetic polymorphisms in theCYP1A1,GSTM1,GSTT1andGSTP1metabolic genes were not significantly associated with lung cancer risk in the current study. The results of the analysis of gene-gene interactions ofCYP1A1 MspI T6235C,GSTM1present/null,GSTT1present/null andGSTP1Ile105Val polymorphisms in lung cancer risk indicate that these genes do not interact in lung cancer development.