Association of glutathione S-transferase (GSTM1 and GSTT1) genes with chronic myeloid leukemia

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.

Genetic Polymorphism of GSTP1, GSTM1 and GSTT1 Genes and Susceptibility to Chronic Myeloid Leukaemia

“…The above findings were in agreement with a recent study conducted in Sudan (Muddathir et al, 2019). Many studies have focused on the relationship between GSTT1 polymorphism and the risk of CML in diverse ethnic groups (Bajpai et al, 2007;Al-Achkar et al, 2014;Kassogue et al, 2015). These findings were in agreement with this study.…”

“…The development of cancer results from an imbalance between exposure to carcinogens (endogenous and exogenous) and the capacity of various enzyme systems engaged in the activation or detoxification of Xenobiotics. Inter-individual genetic variation in xenobiotic metabolizing enzymes has been associated with cancer development, (Kassogue et al, 2015) and since such a metabolism constitutes an important line of defense against a variety of carcinogens, inherited differences in…”

GST and Mdr1 Gene Polymorphisms in Chronic Myeloid Leukemic Patients

“…Nahla A. et al (2016) in their study indicated that GSTP1 mutant allele may contribute significantly to susceptibility to CML in sample of Egyptian patients (12). In a study done in Moroccan patients(M),Yaya Kassuogue et al (2015) have concluded that the GSTT1 null genotype is associated with the development of CML in males but not in females (13). In patients of Argentina, Weich N et al (2016) came to conclusion that GSTM1 is significantly linked to poor molecular response to treatment of CML.…”

Genetic polymorphism of drug metabolism enzymes (GSTM1, GSTT1 and GSTP1) in the healthy Malian population

“…The PCR reaction mixture consisted of 100 ng of genomic DNA, 1× of 10× Buffer (Invitrogen), 1.5 mM of MgCl2, 0.2 mM of each dNTP, 10 pM of each primer and 0.5 U of Taq polymerase (Invitrogen) completed to 25 µL with molecular grade water. The forwards and reverses primers used for GSTT1, GSTM1 and BCL2 as well as PCR amplification technical aspects were previously described in details by Kassogue et al [21,22]. DNA fragments were analyzed on a 2% agarose gel stained with 0.5 µg/mL ethidium bromide.…”