Glutathione S-transferase P1 genetic polymorphisms and susceptibility to childhood acute lymphoblastic leukaemia.

摘要

Glutathione S-transferase pi (GSTP1) is involved in the metabolism of carcinogens. We assessed the association of GSTP1 genetic polymorphisms and the susceptibility to childhood acute lymphoblastic leukaemia (ALL) by conducting a case-control study on 278 ALL patients and 303 healthy controls, both of French-Canadian origin. The carriers of the variant (only the Val substitution) were found to be associated with an increased risk of ALL [odds ratio (OR) = 1.5, 95% confidence interval (CI) 1.1-2.0], whereas the variant (both Val and Val ) was underrepresented in cases. Thus, genetic variants of GSTP1 that are expressed at the protein level appear to contribute differently to the risk of ALL, probably because of distinct substrate specificities. When combined with other GST genotypes, we found that the combination of and null genotypes further increased the risk of ALL (OR = 2.1; 95% CI-1.3-3.4). These findings suggest that GSTP1 variants (alone or combined with other GSTs) represent significant genetic determinants of childhood ALL.