title: Genetic polymorphisms and haplotypes of DNA repair genes in childhood acute lymphoblastic leukemia.
abstract: BACKGROUND
  Polymorphisms of DNA repair genes can alter protein structure and may impair DNA repair capacity. Defects in repairing damaged DNA lead to genetic instability and carcinogenesis. This study was performed to evaluate the effect of the polymorphisms of DNA repair genes on risk of childhood acute lymphoblastic leukemia (ALL).
  
  
  METHODS
  We genotyped polymorphisms of X-ray repair cross-complimenting group 1 (XRCC1) codon 194 (Arg to Trp), 280 (Arg to His) and 399 (Arg to Gln), and xeroderma pigmentosum group D (XPD) codon 312 (Asp to Asn) and 715 (Lys to Gln) in 108 children with ALL and 317 healthy controls using PCR-RFLP method. The allele, genotype, and haplotype frequencies of these polymorphisms were compared between cases and controls using Chi-square or Fisher's exact test. PHASE computer software was used to analyze estimated haplotypes of the XRCC1 and XPD polymorphisms.
  
  
  RESULTS
  The frequency of XRCC1 194Trp allele in patients was significantly lower than that in controls (odds ratio (OR) 0.67; 95% confidence interval (CI), 0.47-0.97). Individuals with XRCC1 194 Trp/Trp genotype had a significantly reduced risk of ALL (OR 0.22; 95% CI, 0.05-0.96). The frequency of the XRCC1 haplotype B (194Trp-280Arg-399Arg) was significantly lower in children with ALL when compared to controls. The XRCC1 399Gln allele was associated with a significantly increased risk of ALL (OR 1.67; 95% CI, 1.20-2.33). The frequency of the XRCC1 haplotype C (194Arg-280Arg-399Gln) was significantly higher in patients. There was no difference of allele frequencies of the XRCC1 280 (Arg to His), XPD 312 (Asp to Asn), or XPD 715 (Lys to Gln) between cases and controls.
  
  
  CONCLUSIONS
  The XRCC1 194Trp allele and haplotype B showed a protective effect against development of childhood ALL. In contrast, individuals with the XRCC1 399Gln allele and haplotype C were associated with increased risk for this disease.
authors.affiliation: Departments of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Rama VI Road, Rajthevi, Bangkok, Thailand. rasam@mahidol.ac.th
authors.forename: Samart
authors.initials: S
authors.lastname: Pakakasama
authors.forename: Tanasan
authors.initials: T
authors.lastname: Sirirat
authors.forename: Saowanee
authors.initials: S
authors.lastname: Kanchanachumpol
authors.forename: Umaporn
authors.initials: U
authors.lastname: Udomsubpayakul
authors.forename: Surakameth
authors.initials: S
authors.lastname: Mahasirimongkol
authors.forename: Pimpun
authors.initials: P
authors.lastname: Kitpoka
authors.forename: Amnuay
authors.initials: A
authors.lastname: Thithapandha
authors.forename: Suradej
authors.initials: S
authors.lastname: Hongeng
mesh_terms: D000293:Adolescent; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007223:Infant; D008297:Male; D020125:Mutation, Missense; D011110:Polymorphism, Genetic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human