title: Genetic polymorphisms of DNA double-strand break repair pathway genes and glioma susceptibility.
abstract: BACKGROUND
  Genetic variations in DNA double-strand break repair genes can influence the ability of a cell to repair damaged DNA and alter an individual's susceptibility to cancer. We studied whether polymorphisms in DNA double-strand break repair genes are associated with an increased risk of glioma development.
  
  
  METHODS
  We genotyped 10 potentially functional single nucleotide polymorphisms (SNPs) in 7 DNA double-strand break repair pathway genes (XRCC3, BRCA2, RAG1, XRCC5, LIG4, XRCC4 and ATM) in a case-control study including 384 glioma patients and 384 cancer-free controls in a Chinese Han population. Genotypes were determined using the OpenArray platform.
  
  
  RESULTS
  In the single-locus analysis there was a significant association between gliomas and the LIG4 rs1805388 (Ex2 +54C>T, Thr9Ile) TT genotype (adjusted OR, 3.27; 95% CI, 1.87-5.71), as well as the TC genotype (adjusted OR, 1.62; 95% CI, 1.20-2.18). We also found that the homozygous variant genotype (GG) of XRCC4 rs1805377 (IVS7-1A>G, splice-site) was associated with a significantly increased risk of gliomas (OR, 1.77; 95% CI, 1.12-2.80). Interestingly, we detected a significant additive and multiplicative interaction effect between the LIG4 rs1805388 and XRCC4 rs1805377 polymorphisms with an increasing risk of gliomas. When we stratified our analysis by smoking status, LIG4 rs1805388 was associated with an increased glioma risk among smokers.
  
  
  CONCLUSIONS
  These results indicate for the first time that LIG4 rs1805388 and XRCC4 rs1805377, alone or in combination, are associated with a risk of gliomas.
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China. zhaopeng@njmu.edu.cn
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
authors.forename: Peng
authors.initials: P
authors.lastname: Zou
authors.forename: Lin
authors.initials: L
authors.lastname: Zhao
authors.forename: Wei
authors.initials: W
authors.lastname: Yan
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Kang
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.forename: Yongping
authors.initials: Y
authors.lastname: You
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D016001:Confidence Intervals; D004265:DNA Helicases / Q000235:genetics; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D024522:Genes, BRCA2; D016654:Genes, RAG-1; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D005910:Glioma / Q000235:genetics*; D006801:Humans; D000072200:Ku Autoantigen; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide
chemical_list: D004268:DNA-Binding Proteins; C000607893:LIG4 protein, human; C110901:X-ray repair cross complementing protein 3; C101467:XRCC4 protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D004265:DNA Helicases; C106893:XRCC5 protein, human; D000072200:Ku Autoantigen; D011088:DNA Ligases; D000072481:DNA Ligase ATP