title: Analysis of DNA repair gene polymorphisms in glioblastoma.
abstract: BACKGROUND
  Glioblastoma is the most common and aggressive primary brain tumor in adults. Despite several factors such as ionizing radiation exposure or rare genetic syndromes have been associated with the development of glioblastoma, no underlying cause has been identified for the majority of cases. We thus aimed to investigate the role of DNA repair polymorphisms in modulating glioblastoma risk.
  
  
  METHODS
  Genotypic and allelic frequencies of seven common polymorphisms in DNA repair genes involved in nucleotide excision repair (ERCC1 rs11615, ERCC2 rs13181, ERCC6 rs4253079), base excision repair (APEX1 rs1130409, XRCC1 rs25487), double-strand break repair (XRCC3 rs861539) and mismatch repair (MLH1 rs1800734) pathways were analyzed in 115 glioblastoma patients and 200 healthy controls. Haplotype analysis was also performed for ERCC1 rs11615 and ERCC2 rs13181 polymorphisms, located on the same chromosomal region (19q13.32).
  
  
  RESULTS
  Our results indicated that carriers of the ERCC2 Gln/Gln genotype were associated with a lower glioblastoma risk (OR=0.32, 95% CI 0.12-0.89; P=0.028), whereas carriers of the MLH1 AA genotype were associated with an increased risk of glioblastoma (OR=3.14, 95% CI 1.09-9.06; P=0.034). Furthermore, the haplotype containing the C allele of ERCC2 rs13181 polymorphism and the T allele of ERCC1 rs11615 polymorphism was significantly associated with a protective effect of developing glioblastoma (OR=0.34, 95% CI 0.16-0.71; P=0.004).
  
  
  CONCLUSIONS
  These results pointed out that MLH1 rs1800734 and ERCC2 rs13181 polymorphisms might constitute glioblastoma susceptibility factors, and also suggested that the chromosomal region 19q could be important in glioblastoma pathogenesis.
authors: Molecular Medicine Unit, Department of Medicine, University of Salamanca, Salamanca, Spain; IBMCC and IBSAL (USAL/CSIC/University Hospital), Salamanca, Spain.
authors: Irene
authors: I
authors: Rodriguez-Hernandez
authors: IINGM El Bosque University, Bogota, Colombia.
authors: Sandra
authors: S
authors: Perdomo
authors: IBMCC and IBSAL (USAL/CSIC/University Hospital), Salamanca, Spain; Department of Pathology, University Hospital of Salamanca, Salamanca, Spain.
authors: Angel
authors: A
authors: Santos-Briz
authors: IBMCC and IBSAL (USAL/CSIC/University Hospital), Salamanca, Spain; Institute for Health Science Studies of Castilla y Leon, Salamanca, Spain.
authors: Juan Luis
authors: JL
authors: Garcia
authors: Department of Neurosurgery, University Hospital of Salamanca, Salamanca, Spain.
authors: Juan Antonio
authors: JA
authors: Gomez-Moreta
authors: IBMCC and IBSAL (USAL/CSIC/University Hospital), Salamanca, Spain; Department of Oncology, University Hospital of Salamanca, Salamanca, Spain.
authors: Juan Jesus
authors: JJ
authors: Cruz
authors: Molecular Medicine Unit, Department of Medicine, University of Salamanca, Salamanca, Spain; IBMCC and IBSAL (USAL/CSIC/University Hospital), Salamanca, Spain. Electronic address: gonzalez@usal.es.
authors: Rogelio
authors: R
authors: Gonzalez-Sarmiento
mesh_terms: D000368:Aged; D001932:Brain Neoplasms / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D004260:DNA Repair / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005909:Glioblastoma / Q000453:epidemiology / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
keywords: APEX nuclease (multifunctional DNA repair enzyme) 1; APEX1; BER; DSBR; ERCC1; ERCC2; ERCC6; Glioblastoma; MLH1; MMR; NER; PCR; Polymorphism; Repair; X-ray repair complementing defective repair in Chinese hamster cells 1; X-ray repair complementing defective repair in Chinese hamster cells 3; XRCC1; XRCC3; base excision repair; double-strand break repair; excision repair cross-complementing rodent repair deficiency, complementation group 1; excision repair cross-complementing rodent repair deficiency, complementation group 2; excision repair cross-complementing rodent repair deficiency, complementation group 6; mismatch repair; mutL homolog 1; nucleotide excision repair; polymerase chain reaction