DNA repair gene variants are associated with an increased risk of myelodysplastic syndromes in a Czech population

Monika Belickova,Dana Sponerova,Michaela Dostalova Merkerova,Dana Mikulenkova,Anna Jonasova,Radim Brdicka,Jitka Vesela,Eliska Stara,Radana Neuwirtova,Jaroslav Cermak

doi:10.1186/1756-8722-6-9

Abstract

BackgroundInteractions between genetic variants and risk factors in myelodysplastic syndromes are poorly understood. In this case–control study, we analyzed 1 421 single nucleotide polymorphisms in 408 genes involved in cancer-related pathways in 198 patients and 292 controls.MethodsThe Illumina SNP Cancer Panel was used for genotyping of samples. The chi-squared, p-values, odds ratios and upper and lower limits of the 95% confidence interval were calculated for all the SNPs that passed the quality control filtering.ResultsGene-based analysis showed nine candidate single nucleotide polymorphisms significantly associated with the disease susceptibility (q-value < 0.05). Four of these polymorphisms were located in oxidative damage/DNA repair genes (LIG1, RAD52, MSH3 and GPX3), which may play important roles in the pathobiology of myelodysplastic syndromes. Two of nine candidate polymorphisms were located in transmembrane transporters (ABCB1 and SLC4A2), contributing to individual variability in drug responses and patient prognoses. Moreover, the variations in the ROS1 and STK6 genes were associated with the overall survival of patients.ConclusionsOur association study identified genetic variants in Czech population that may serve as potential markers for myelodysplastic syndromes.

Highlights

Myelodysplastic syndromes (MDS) are heterogeneous hematopoietic diseases characterized by ineffective hematopoiesis that frequently transform into acute leukemia
Five of the polymorphisms described in our study are located close to areas that are frequently deleted in MDS
The genetic variants detected in this study are likely to be biologically relevant, the polymorphisms in oxidative damage/ DNA repair genes (LIG1, RAD52, MSH3 and glutathione peroxidase 3 (GPX3)), which may play important roles in the pathobiology of MDS

Summary

Introduction

Myelodysplastic syndromes (MDS) are heterogeneous hematopoietic diseases characterized by ineffective hematopoiesis that frequently transform into acute leukemia. Because genetic background is thought to influence the risk of developing MDS, several case– control studies have investigated the relationships between specific genetic polymorphisms and the risk of MDS [1,2,3,4,5]. The GSTP1 (glutathione S-transferase pi 1) - 105Val allele has been reported to be associated with an increased risk of MDS [3]. Interactions between genetic variants and risk factors in myelodysplastic syndromes are poorly understood. In this case–control study, we analyzed 1 421 single nucleotide polymorphisms in 408 genes involved in cancer-related pathways in 198 patients and 292 controls

Methods

Results

Conclusion