Prevalence of GSTT1, GSTM1 and NQO1 (609C>T) in Filipino children with ALL (acute lymphoblastic leukaemia)

Abstract

In the present paper, we examined the incidence of polymorphic genes involved with the detoxification of exogenous chemicals, including carcinogens, namely GSTT1 (glutathione transferase theta1), GSTM1 (glutathione transferase micro1) and NQO1 (NAD(P)H:quinone oxidoreductase 1) in 60 Filipino paediatric patients with ALL (acute lymphoblastic leukaemia). We found a significantly high incidence of the GSTM1 null genotype in ALL children (71.7%) compared with 51.7% in the control group of children (P<0.05). The GSTT1 null genotype was observed in 35.0% and 33.3% of the ALL cases and the control subjects respectively, with no significant difference. Screening for NQO1 (609C>T) mutant alleles showed a high incidence of the NQO1 C/C genotype (NQO1 homozygous wild-type allele genotype) in 60.0% of ALL cases and was significantly higher than in the control group (23.3%) (P<0.01). These GSTM1 null and NQO1 wild-type genotypes are independently associated with the risk of ALL in Filipino patients. When these two genotypes, GSTM1 null and NQO1 C/C, were combined, the hazard rate for childhood leukaemia was significantly increased (P<0.001). We also noticed that the incidences of GSTM1 null mutations and the NQO1 C/C genotype were significantly higher among Filipinos. These findings suggest a possible role of the GSTM1 null and NQO1 C/C genotypes in the susceptibility of paediatric ALL cases in the Philippines.

Genetic polymorphisms of NQO1, CYP1A1 and TPMT and susceptibility to acute lymphoblastic leukemia in a Tunisian population

“…Indeed, it is well known that the wild NQO1 enzyme protects the cell against the oxidative stress and toxic quinone [35,36] and stabilizes the p53 protein [37,38]. In opposition to our results other authors have found a positive association between the NQO1 CC (homozygous wild genotype) and the increased risk of ALL [39]. Authors explain this association by the role of wild NQO1 enzyme in activating carcinogens aside from detoxification.…”

Associations of NQO1 C609T and NQO1 C465T polymorphisms with acute leukemia risk: a PRISMA-compliant meta-analysis

“…Among the articles, 18 and 18 were about the associations of the NQO1 C609T polymorphism with the risks of AML and ALL, respectively, two were about the association between the NQO1 C465T polymorphism and the AML risk, and three were about the association between the NQO1 C465T polymorphism and the ALL risk. Among these studies, 11 focused on Caucasians,1,3,12–20 10 on Asians,2,9,10,21–27 four on mixed populations,5,28–30 two on Africans,31,32 and one on Javanese 33. In terms of the genotype distribution of controls, 20 of the studies about the association between the NQO1 C609T polymorphism and the AL risk conformed with HWE,1,3,5,9,12,14–20,22–24,28,30–33 while seven did not,2,10,21,25–27,29 and the HWE test could not be applied to one study13 because of insufficient data.…”

“…In addition, the influence analysis of single study showed that the total pooled result was greatly affected by the 15 studies (Figure 2B). 2,3,9,10,12,13,15,16,19,21,25,28–31 Excluding any of these studies resulted in the statistically significant loss of pooled OR values. Meanwhile, the sensitivity analysis revealed that deleting two studies of low quality,2,13 five studies that did not conform to HWE,2,10,21,25,29 or one study for which the HWE test was not applied did not change the pooled ORs,13 showing that these factors did not affect the stability of the pooled results.…”

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

“…Rest of the studies are from southern part of India which has a different genetic pool compared with the north. 12,13 We also reviewed the previously published studies [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] (between 1997 and January 2014) and performed a meta-analysis examining the association of GST gene variation and susceptibility to childhood ALL.…”