title: DNA repair gene variants are associated with an increased risk of myelodysplastic syndromes in a Czech population.
abstract: BACKGROUND
  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
  The 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.
  
  
  RESULTS
  Gene-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.
  
  
  CONCLUSIONS
  Our association study identified genetic variants in Czech population that may serve as potential markers for myelodysplastic syndromes.
authors: Institute of Hematology and Blood Transfusion, U Nemocnice 1, Prague, Czech Republic. monika.belickova@uhkt.cz
authors: Monika
authors: M
authors: Belickova
authors: Michaela Dostalova
authors: MD
authors: Merkerova
authors: Eliska
authors: E
authors: Stara
authors: Jitka
authors: J
authors: Vesela
authors: Dana
authors: D
authors: Sponerova
authors: Dana
authors: D
authors: Mikulenkova
authors: Radim
authors: R
authors: Brdicka
authors: Radana
authors: R
authors: Neuwirtova
authors: Anna
authors: A
authors: Jonasova
authors: Jaroslav
authors: J
authors: Cermak
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D018153:Czech Republic / Q000453:epidemiology; D004260:DNA Repair / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000453:epidemiology / Q000209:etiology* / Q000401:mortality; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate; D055815:Young Adult
chemical_list: D004273:DNA, Neoplasm; D045643:DNA Repair Enzymes