The GSTP1 A1578G polymorphism and the risk of childhood acute lymphoblastic leukemia: results from an updated meta-analysis

Abstract

ABSTRACT. Studies investigating the association between the glutathione S-transferase P1 (GSTP1) A1578G polymorphism and the risk of childhood acute lymphoblastic leukemia (ALL) report conflicting results. The aim of this study was to quantitatively summarize the evidence for such a relationship. Two investigators independently searched the Medline, Embase, China National Knowledge Infrastructure, and Wangfang databases for studies of the polymorphism and ALL. Summary odds ratios (ORs) and 95% confidence intervals (CIs) for the GSTP1 polymorphism and childhood ALL were calculated in a fixed-effect model. Pooled ORs were calculated for a co-dominant model (GG vs AA, AG vs AA), a dominant model (GG + AG vs AA), and a recessive model (GG vs AA + AG). Analyses were also performed in subgroups stratified by race, study design, genotyping methods, and study sample size. This meta-analysis included 8 case-control studies with 1384 childhood ALL cases and 1755 controls. Overall, the variant genotypes (GG and AG) of A1578G were not associated with childhood No heterogeneity or publication bias was observed in the present study. This updated meta-analysis indicates that the GSTP1 A1578G polymorphism is not associated with the risk of childhood ALL. In the future, additional studies in Asian and African-American patients should be performed to re-evaluate the association in these populations.

Glutathione-S-transferase polymorphism and acute lymphoblastic leukemia (ALL) in north Indian children: a case–control study and meta-analysis

“…Our findings pertaining to the GSTM1 genotype is in agreement with all the previously conducted meta-analyses, 3,[32][33][34][35][36] while that pertaining to GSTT1 compared favorably with some 33,34 while disagreeing with others. 32,35,36 None of the earlier meta-analyses found any association between GSTP1 polymorphism and risk of childhood ALL.…”

“…We combined 22, 10 and 20 studies each for GSTM1, GSTP1 and GSTT1 genes respectively including larger number of subjects compared with the previous meta-analyses. 3,[32][33][34][35][36] We also noted a considerable lack of studies among Black subjects, only two studies examined the association of GSTM1 and GSTT1 in a limited number of Black subjects (n ¼ 473). No GSTP1-related study conducted among the Blacks was noted by us.…”

“…2 Children are vulnerable to environmental toxins more than adults because of their relatively greater exposure, immature metabolism and higher levels of cell division and growth. 2,3 Existence of an effective detoxifying enzyme system helps in the metabolism of potentially harmful environmental toxins to inactive metabolites thereby imparting protection from development of cancer. 3 Glutathione S-transferase (GST) M1, P1 and T1 are phase II enzymes involved in metabolism and detoxification of reactive oxygen species, xenobiotics and carcinogens.…”

“…2,3 Existence of an effective detoxifying enzyme system helps in the metabolism of potentially harmful environmental toxins to inactive metabolites thereby imparting protection from development of cancer. 3 Glutathione S-transferase (GST) M1, P1 and T1 are phase II enzymes involved in metabolism and detoxification of reactive oxygen species, xenobiotics and carcinogens. 4 Genetic variation in this gene family have been associated with increased susceptibility to certain primary as well as chemotherapy-induced second cancers.…”

“…6 Null mutations in GSTM1 and GSTT1 lead to loss in the corresponding enzyme activity 6 whereas 1578 A4G transition leads to reduction in GSTP1 activity. 3 The association of GST polymorphisms and childhood ALL was reported in 1997 for the first time, 7 which led a number of subsequent investigators to examine the association and arrive at conflicting results. Previous studies from India studying this association also reached different conclusions.…”