Genetic polymorphisms in CYP1A1 , GSTM1 , GSTP1 and GSTT1 metabolic genes and risk of lung cancer in Asturias

Abstract

Doc number: 433

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 the CYP1A1 MspI T6235C, GSTM1 present/null , GSTT1 present/null and GSTP1 Ile105Val polymorphisms 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 the CYP1A1 , GSTM1 , GSTT1 and GSTP1 metabolic genes were not significantly associated with lung cancer risk in the current study. The results of the analysis of gene-gene interactions of CYP1A1 Msp I T6235C, GSTM1 present/null, GSTT1 present/null and GSTP1 Ile105Val polymorphisms in lung cancer risk indicate that these genes do not interact in lung cancer development.