Glutathione S-transferase T1 null-genotype is associated with an increased risk of lung cancer

Glutathione S-transferases (GSTs) are involved in detoxification of carcinogens, e.g., from tobacco smoke. Therefore, polymorphisms in the GST genes have been considered as potential modifiers of individual cancer risk. In a population-based case-cohort study where cases and the subcohort sample were matched on duration of smoking, we investigated the occurrence of lung cancer and histological subtypes of lung cancer in relation to deletion polymorphism in both GSTMI and GSTTI, single nucleotide polymorphisms (SNPs) in GSTPI (Ile105Val and Alal 14Val) and a 3 base pair deletion polymorphism in GSTM3. We further investigated the effects of the GST polymorphisms on lung cancer risk within subgroups of subjects defined by gender and age. The results showed a 2.4-fold (CI = 1.31-4.41) increased risk of lung cancer in GSTTI null-genotype carriers but no significant effects of the polymorphisms in GSTMI, GSTM3, GSTPI-105 or GSTPI-114. The association was strongest in lower age groups, with a 9.6-fold increase in risk for subjects with the GSTT I null-genotype in the 50-55 years age interval (CI = 3.03-30.59). Positive associations were found for GSTT I within all major histological subtypes. Squamous cell carcinoma was the histological type most strongly associated with the I genotype, with a 5.0-fold (Cl = 2.26-11.18) increase in risk for subjects carrying the GSTTI null-genotype. The effects of the GSTT I null-genotype seemed stronger in the presence of the GSTMI null-genotype or the GSTPI-105 variant allele. These results suggest that the GSTT I null-genotype is associated with an increased risk of lung cancer, especially in younger individuals. (C) 2004 Wiley-Liss, Inc.