XRCC3 Thr241Met polymorphism and risk of acute myeloid leukemia in a Romanian population

Abstract

Background: DNA repair systems have a critical role in maintaining the genome integrity and stability. DNA repair gene polymorphisms may influence the capacity to repair DNA damage, and thus lead to an increased cancer susceptibility. X-ray repair cross-complementing groups 3 (XRCC3), a DNA repair gene, may be involved in acute myeloid leukemia susceptibility. The objective of the current study was to investigate the association of Thr241Met polymorphism of XRCC3 gene with the risk of acute myeloid leukemia (AML).

Methods: This study included 78 AML patients and 121 healthy individuals without cancer. We used polymerase chain reaction-restriction fragment length polymorphism assay to determine XRCC3 genotypes.

Results: The XRCC3 variant genotype (Thr/Met+Met/Met) was more frequent in AML patients than in healthy controls (OR=2.76, 95% CI: 1.52-4.98, P=0.001). Our study revealed a statistically significant association between variant genotype (Thr/Met+Met/Met) and AML de novo compared to secondary AML (P=0.007). No significant associations were found between any genotype and age at diagnosis, number of white blood cells and subtype of AML. Overall survival of patients with Thr/Thr genotype was better than those of variant Thr/Met and Met/Met genotypes.

Conclusions: Our findings indicate that the XRCC3 Thr241Met polymorphism may be a genetic risk factor for AML, particularly in male patients with de novo AML from the central part of Romania.

Keywords: AML; FLT3; HR; ITD; OR; OS; Overall survival; PCR-RFLP; Variant genotype; X-ray repair cross-complementing group 3; X-ray repair cross-complementing groups 3; XRCC3; acute myeloid leukemia; fms-like tyrosine kinase 3; hazard ratio; internal tandem duplication; odd ratio; overall survival; polymerase chain reaction-restriction fragment length polymorphism.