Abstract

Chronic myeloid leukemia (CML), as most of cancers results from a complex interaction between genetic or non genetic factors. Exposures to xenobiotics endogenous or exogenous associated with a reduced individual ability in detoxifying activity, constitutes a risk of developing cancer. It is known that polymorphism of glutathione S-transferases (GSTs) genes affects the detoxification of xenobiotics. Thus, we conducted a case-control study in which 92 patients (Mean age ± SD, 40.62 ± 12.7 years) with CML and 93 healthy unrelated controls (Mean age ± SD, 41.38 ± 13.4 years) have participated. GSTM1 and GSTT1 genotypes were determined by multiplex polymerase chain reaction. Logistic regression was used to assess the possible link between GSTM1 and GSTT1 null genotypes and CML as well as between combined genotypes and CML. GSTM1 null genotype frequency was slightly higher in patients than control (48.9% vs. 40.9%) but, it was not associated with CML (OR 95% CI, 1.4, 0.78-2.48; p = 0.271). Moreover, GSTT1 null genotype frequency showed a similar trend between patients and control (17.4% vs. 9.7%; OR 95% CI, 1.97, 0.82-4.71; p = 0.13). Surprisingly, GSTT1 null genotype was significantly associated with the risk of CML in males (OR 95% CI, 5, 1.25-20.1; p = 0.023). The combined GSTM1 present/GSTT1 null genotype was found to have a limited effect against the risk of CML (OR 95% CI, 0.3, 0.08-0.99; p = 0.049). Our findings have shown that GSTT1 null genotype might be a risk factor of CML in males. While, GSTT1 present genotype might be considered as protective against CML. However, further studies with a large sample size are needed to confirm our findings.

Highlights

  • Chronic myeloid leukemia (CML) is a blood cancer secondary to the presence of the reciprocal translocation t(9; 22)(q34; q11) or BCR-ABL gene fusion causing a malignant proliferation of hematopoietic cells (Deininger et al 2000)

  • We have used the statistical package SPSS version 16 (SPSS Inc., Chicago, IL, USA). In this case-control study, we explored the frequency of GSTM1 and GSTT1 genotypes in CML patients and controls

  • We found that the GSTM1 null genotype was moderately more frequent in patients (48.9%) compared to control (40.9%), this difference was not statistically significant

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Summary

Introduction

Chronic myeloid leukemia (CML) is a blood cancer secondary to the presence of the reciprocal translocation t(9; 22)(q34; q11) or BCR-ABL gene fusion causing a malignant proliferation of hematopoietic cells (Deininger et al 2000). The etiology of CML like most of cancers, results from a complex interaction between several factors, among others exposure to ionizing and non ionizing radiation, carcinogens present in the environment such as benzene, smoke and pesticides (Salagovic et al 2000; Gervasini et al 2007). These factors considered as genotoxics may affect the biotransformation of xenobiotics and cause damage to the DNA of hematopoietic cells and foster the occurrence of CML (Belitsky & Yakubovskaya 2008). Given the absence of data on the frequencies of GSTM1 and GSTT1 genotypes in our population, we decided to carry out this case-control study with the aim to establish firstly their frequencies in the population and secondly estimate the possible link between the null genotypes and the occurrence of chronic myeloid leukemia in a sample of the Moroccan population

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