Polymorphic variation within the glutathione S-transferase genes and risk of adult acute leukaemia

Abstract

Polymorphisms within the phase II metabolizer enzymes GST T1, GST M1 and GST P1 affect the body's ability to detoxify a range of potential leukaemogens encountered in the environment. Using PCR, GST T1, GST M1 and GST P1 genotypes were determined in 557 adults with acute leukaemia and 952 age, sex and geographically matched controls. The strongest association with acute leukaemia was observed for the GST T1 null genotype, which occurred among 19% of cases and 14% of controls [odds ratio (OR) 1.45, 95% confidence interval (CI) 1.09-1.93]. A slightly higher proportion of cases (53%) than controls (49%) displayed the GST M1 null genotype, although the difference was not statistically significant (OR 1.22, 95% CI 0.98-1.52). No effect was observed for the GST P1 genotype and no interaction between the GST T1 and GST M1 genotypes was evident. Acute myeloid leukaemia (AML) was weakly associated with both GST T1 null (OR 1.32, 95% CI 0.97-1.79) and GST M1 null (OR 1. 24, 95% CI 0.98-1.56), whereas acute lymphoblastic leukaemia (ALL) was associated with GST T1 null (OR 3.28, 95% CI 1.31-8.26). No associations between smoking and disease risk in relation to GST T1 and GST M1 polymorphic status were found.