Genetic polymorphisms of GSTM1, GSTP1 and GSTT1 genes and lung cancer susceptibility in the Bangladeshi population

Abstract

Objective: To verify possible associations between polymorphisms of glutathione S-transferase Mu (GSTM1), glutathione S-transferase θ (GSTT1) and glutathione S-transferase Pi (GSTP1) genes and susceptibility to lung cancer. Methods: A total of 106 lung cancer patients and 116 controls were enrolled in a case-control study. The GSTM1 and GSTT1 were analyzed using PCR while GSTP1 was analyzed using PCR-restriction fragment length polymorphism. Risk of lung cancer was estimated as odds ratio at 95% confidence interval using unconditional logistic regression models adjusting for age, sex, and tobacco use. Results: GSTM1 null and GSTT1 null genotypes did not show a significant risk for developing lung cancer. A significantly elevated lung cancer risk was associated with GSTP1 heterozygous, mutant and combined heterozygous+mutant variants of rs1695. When classified by tobacco consumption status, no association with risk of lung cancer was found in case of tobacco smokers and nonsmokers carrying null and present genotypes of GSTM1 and GSTT1. There is a three-fold (approximately) increase in the risk of lung cancer in case of both heterozygous (AG) and heterozygous+mutant homozygous (AG+GG) genotypes whereas there is an eight-fold increase in risk of lung cancer in cases of GG with respect to AA genotype in smokers. Conclusions: Carrying the GSTM1 and GSTT1 null genotype is not a risk factor for lung cancer and GSTP1Ile105Val is associated with elevated risk of lung cancer.

Keywords

• Lung cancer
• Glutathione S-transferase
• Genetic polymorphism
• Smoking