GST T1 and GST M1 Polymorphisms Are Associated with the Risk of Acute Myeloid Leukemia

Xenobiotic-metabolizing enzymes influence the susceptibility to malignancies as well as prognosis by causing chemotherapy resistance. We analyzed genetic polymorphisms of glutathione S-transferases T1 and M1 (del GSTT1 and del GSTM1) and NAD(P)H quinone-oxoreductase (NQO1 C609T) to evaluate the association and risk of acute myeloid leukemia (AML). A large-scale population-based, case-control study of 1700 controls and 663 cases was conducted in Chonnam National University Hwasun Hospital, Korea.

GST T1 null genotype was associated with increased risk for AML [odds ratio (OR) = 1.20; 95% confidence interval (CI) = 1.003–1.45, p=0.047]. GST M1 null genotype was highly associated with a decreased risk for AML (OR= 0.38; 95%CI = 0.31–0.46, p< 0.0001). Analysis of the NQO1 C609T polymorphism failed to show an association with AML, although a near significant increase was also found in NQO1 609GG genotype (OR= 1.30; 95%CI = 0.54–4.77, p=0.06)

Our results suggest an association of extensive GST with an increased or decreased risk for AML, possibly by an increase in the metabolic activation of chemical carcinogens or linkage to another cancer-causing gene. Inconsistent result in other studies may be due to geographical differences in the type of environmental carcinogens to which different populations are exposed.