Association of Glutathione S-Transferase, EPHX, and p53 codon 72 Gene Polymorphisms with Adult Acute Myeloid Leukemia

Abstract

Polymorphisms in genes encoding detoxification enzymes have been suggested as susceptibility factors for many solid tumors. However, their association with hematological malignancies is controversial. A case-control study was done to determine the association between glutathione S-transferase M1 (GSTM1), GSTT1, GSTP1, EPHX1, and p53 codon 72 polymorphisms as risk factors in 120 adult acute myeloid leukemia (AML) cases and 202 healthy controls by polymerase chain reaction-restriction fragment length polymorphism techniques. Data were analyzed using χ(2) and conditional logistic regression model. None of the polymorphisms studied alone was associated with increased risk for AML. However, the frequency of GSTT1 null genotype was higher among controls (28.7%) than AML cases (21.6%), which showed a protective effect of the null genotype (odds ratio = 0.58, 95% confidence interval: 0.33-1.05, p = 0.07). In a combined analysis, both EPHX1 (His113His) and GSTP1 (Ile/Val) genes imparted a fourfold risk for adult AML but did not reach statistical significance (odds ratio = 4.22, 95% confidence interval: 0.992-17.99, p = 0.05). These findings suggest that the etiology of adult AML cannot be explained by polymorphism at a single locus, perhaps because of complexity involved in the metabolism of diverse xenobiotic compounds, and therefore, multiple gene-gene interactions should be investigated to predict the risk of AML.

Glutathione-S-Transferase Polymorphisms (GSTM1, GSTT1 and GSTP1) and Acute Leukemia Risk in Asians: a Meta-analysis

“…There were some evidences of heterogeneity across studies. Seven studies were the major sources of heterogeneity (Sasai et al, 1999;Yuan et al, 2003;Zou et al, 2004;Aydin-Sayitoglu et al, 2006;Majumdar et al, 2008;Chauhan et al, 2011;Dunna et al, 2013). It might attribute to uncontrolled confounding and inherent bias of study design.…”

“…Several studies used subjects from hospital (Yuan et al, 2003;Liu et al, 2005;Gatedee et al, 2007;Jiang et al, 2008;Suneetha et al, 2008;Jiang et al, 2010;Suneetha et al, 2011;Li et al, 2012). Numerous of studies used samples matched age and sex (Zhang et al, 2003;Joseph et al, 2004;Haranatha et al, 2006;Jiang et al, 2008;Jiang et al, 2010;Chauhan et al, 2011;Dunna et al, 2013), however, others had not. Some studies used samples may have heterogeneous ethnic origin.…”

“…However, when four outlying studies were excluded (Aydin-Sayitoglu et Majumdar et al, 2008;Chauhan et al, 2011;Dunna et al, 2013), the heterogeneity was no longer statistically significant, with the amended overall OR was 1.41 (95% CI 1.27-1.57). The pooled ORs were 1.58 (95% CI 1.14-2.20) and 1.39 (95% CI 1.02-1.90), respectively, in AML and ALL (Table 4).…”

“…Heterogeneity between studies was shown for both ALL and AML. For AML, after three outlying studies were excluded (Majumdar et al, 2008;Chauhan et al, 2011;Dunna et al, 2013), the heterogeneity was no longer statistically significant, with the amended OR was 1.24 (95% CI 1.06-1.45). And for ALL, after one outlying study were excluded (AydinSayitoglu et al, 2006), the heterogeneity was no longer statistically significant, with the amended OR was 1.56 (95% CI 1.36-1.79).…”

Glutathione S-transferase Gene Polymorphisms and Susceptibility to Acute Myeloid Leukemia: Meta-analyses

“…The etiology of AML was found to be multifactorial; however, exposure to carcinogens such as benzene and ionizing radiation is thought to result in DNA damage at the level of hematopoietic progenitor cells, which is an essential prerequisite for the development of AML (2).…”