COMBINED EFFECT OF POLYMORPHIC GST GENES ON INDIVIDUAL SUSCEPTIBILITYTO LUNG-CANCER

Glutathione S-transferases (GSTs) are known to take part in detoxifica tion of many potentially carcinogenic compounds. Therefore, polymorphi sms of the CST genes have been considered as potentially important mod ifiers of individual risk of environmentally induced cancers. The asso ciation between lack of glutathione S-transferase MI gene (GSTM1 null genotype) and susceptibility to smoking-related lung cancer has been a ctively studied, with contradictory results. In contrast, little is kn own about the more recently found polymorphisms in GSTM3, GSTP1 and GS TT1 genes with respect to individual responses to environmental exposu res. In this study, we determined the genotype distribution of all the se genes, and their combinations, among 208 Finnish lung cancer patien ts and 294 population controls. None of the genotypes studied had a st atistically significant effect on lung cancer risk, when studied separ ately. However, a significant association was observed for concurrent lack of the GSTM1 and GSTT1 genes and susceptibility to squamous cell carcinoma. For that cell type, the risk was more than 2-fold when comp ared with that of individuals having other genotype combinations (OR = 2.3; 95% CI = 1.0-5.3; p = 0.05). Moreover, the risk was mostly attri butable to patients with smoking history of 40 pack-years or less (OR = 2.9; 95% CI = 1.1-7.7; P = 0.03). In contrast, this genotype combina tion did not affect the risk for other histological types of lung canc er, and the other genotype combinations had no effects on individual s usceptibility to this malignancy. The overall role of GST polymorphism s in modifying the lung cancer risk may therefore be more limited than has been so far anticipated. Int J. Cancer 77:5 16-521, 1998. (C) 199 8 Wiley-Liss, Inc.