GLUTATHIONE-S-TRANSFERASE POLYMORPHISMS - INFLUENCE ON SUSCEPTIBILITYTO CANCER

The glutathione S-transferase supergene family includes several loci t hat demonstrate well characterised polymorphisms. The apparently criti cal role of these enzymes in cellular protection from the cytotoxic an d mutagenic effects of electrophiles suggest that alleles associated w ith impaired detoxification will confer an increased susceptibility to a wide range of diseases. This hypothesis has been examined in case c ontrol studies and while data in some diseases such as lung cancer are conflicting, an increasing body of evidence suggests the importance o f several glutathione S-transferase polymorphisms. In particular, GST geneotypes have been associated with an increased susceptibility or wo rse outcome in diseases associated with oxidative stress. For example, both GSTM1 and GSTT1 genotypes are associated with susceptibility and outcome in cutaneous basal cell carcinoma. It still remains unclear h owever, why particular glutathione S-transferase loci are associated w ith altered risk in some diseases but not others. Further, the true in vivo substrates of these enzymes is unknown, consequently their mecha nism of action remains unclear. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.