Abstract
Though a developing body of data indicates polymorphism at GST genes influences cancer susceptibility, it is unclear why a genotype is associated with one cancer but not another. We believe the GST exert a critical role in normal cell house-keeping activities. GSTM1, GSTM3 and GSTT1 influence tumorigenesis because these enzymes utilise the products of UV-induced oxidative stress. Further support for the importance of these genes in the protection of skin from UV comes from studies in systemic lupus erythematosus (Ollier et al, 1996). Thus, GSTM1 null is associated with increased anti-Ro (but not anti-La) antibodies, a phenotype associated with photosensitivity. At present there is no basis for predicting which cancers will be influenced by GST polymorphisms though other studies do indicate that the GSTs are critical in the metabolism of environmental carcinogens. For example, GSTT1 null confers an increased risk of astrocytoma (Hand et al, 1996). While brain tumours are not clearly associated with environmental pollutants, N-methyl-N-nitrosourea, processed meats and occupation have been implicated. Why GSTT1 but not GSTM1 or GSTM3 influences the risk of astrocytoma is unclear. GSTM3 appears a good susceptibility candidate, as s...Continue Reading
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