Implications of GSTM1, GSTT1, and GSTP1 polymorphisms for susceptibility to chronic lymphocytic leukemia
Genetic polymorphisms involved in carcinogen metabolism contribute to leukemogenesis risk. Epidemiological studies have revealed genetic alterations in chronic lymphocytic leukemia (CLL), including chromosome alterations, noncoding RNA alterations, and genetic polymorphisms. The bioactivation and detoxification of chemical agents is mediated by xenobiotic metabolism enzymes, and genetic polymorphisms may explain interindividual differences in hematological cancer susceptibility. Glutathione S-transferase (GST) enzymes are capable of metabolizing xenobiotics into less toxic and more easily eliminated substances. Some studies have suggested involvement of GSTs polymorphisms in leukemogenesis susceptibility. We investigated possible genetic associations between GSTM1/GSTT1 deletion and GSTP1 rs1695 polymorphisms with CLL risk in a central Brazilian population. For GSTM1/GSTT1 deletion polymorphism, genotyping was performed with multiplex real-time PCR (qPCR), and for GSTP1 rs1695 polymorphism, PCR-RFLP was used. The GSTM1 null genotype presented a trend towards CLL risk. However, GSTT1 deletion polymorphism presented a protective effect for CLL (OR=0.26, p<0.005).The GSTP1 rs1695 was not associated with disease susceptibility. Among confounding factors, male gender and age was associated with a 2.42-fold and 1.06-fold increased risk of CLL, respectively. In conclusion, among the polymorphisms that were evaluated, the GSTM1 deletion polymorphism apparently helpsin the detoxification process and has a protective effect against CLL.