From Six Gene Polymorphisms of the Antioxidant System, Only GPX Pro198Leu and GSTP1 Ile105Val Modulate the Risk of Acute Myeloid Leukemia.

Claudia Bănescu,Florin Tripon,Adrian P Trifa,Erzsebet Benedek Lazar,Carmen Duicu,Mihaela Iancu,Andrei Crauciuc,Minodora Dobreanu,Valeriu G Moldovan,Marcela Cândea

doi:10.1155/2016/2536705

Abstract

Oxidative stress might contribute to the occurrence of cancers, including the hematological ones. Various genetic polymorphisms were shown to increase the quantity of reactive oxygen species, a phenomenon that is able to induce mutations and thus promote cancers. The purpose of the study was to evaluate the association between CAT C262T, GPX1 Pro198Leu, MnSOD Ala16Val, GSTM1, GSTT1, and GSTP1 Ile105Val gene polymorphisms and acute myeloid leukemia risk, in a case-control study comprising 102 patients and 303 controls. No association was observed between AML and variant genotypes of CAT, MnSOD, GSTM1, and GSTT1 polymorphisms. Our data revealed a statistically significant difference regarding the frequencies of GPX1 Pro198Leu and GSTP1 Ile105Val variant genotypes between AML patients and controls (p < 0.001). Our results showed no association in the distribution of any of the CAT C262T, GPX1 Pro198Leu, GSTM1, GSTT1, and GSTP1 polymorphisms regarding age, gender, FAB subtype, cytogenetic risk groups, FLT3 and DNMT3 gene mutations, and overall survival. Our data suggests that the presence of variant allele and genotype of GPX1 Pro198Leu and GSTP1 Ile105Val gene polymorphisms may modulate the risk of developing AML.

Highlights

Acute myeloid leukemia (AML) is a complex disease characterized by the accumulation of blasts in the bone marrow and uncontrolled proliferation, in which excess production of oxygen derived radicals compromises the antioxidant defense system thereby leading to oxidative stress [1]
There was a significant difference between distributions of GSTP1 Ile105Val allele frequencies in AML group and control subjects (p < 0.0001, odds ratio (OR) = 2.357, and 95% CI: 1.649–3.368)
Environmental carcinogens, physical and chemical exposure, and chemotherapy may lead to acute myeloid leukemia, a heterogeneous disease [18, 31]

Summary

Introduction

Acute myeloid leukemia (AML) is a complex disease characterized by the accumulation of blasts in the bone marrow and uncontrolled proliferation, in which excess production of oxygen derived radicals compromises the antioxidant defense system thereby leading to oxidative stress [1]. Increased production of ROS can lead to acquisition of genomic changes, thereby producing genomic instability This environment can sustain tumor formation and disease progression [7, 8]. Sallmyr et al suggested that FLT3/ITD mutations (FMS-like tyrosine kinase 3, internal tandem duplications) in acute myeloid leukemia (AML) result in ROS production [7]. This may lead to DNA damage and defective repair mechanisms in myeloid leukemia, besides additional chromosomal aberrations and gene mutations

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