title: Association of the genetic polymorphisms in XRCC6 and XRCC5 with the risk of ESCC in a high-incidence region of North China.
abstract: BACKGROUND
  The XRCC6 and XRCC5 genes are part of the nonhomologous end-joining (NHEJ) pathway, which is the main mechanism repairing DNA double-strand breaks (DSBs) in human cells. Genetic variations of XRCC6 and XRCC5 might contribute to esophageal squamous cell carcinoma (ESCC) susceptibility.
  
  
  METHODS
  ESCC patients (n = 189) and cancer-free controls (n = 189) were recruited in an ESCC high-risk area of north China. Then the rs2267437 (XRCC6), rs3835 (XRCC5) and rs16855458 (XRCC5) polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis.
  
  
  RESULTS
  A significant difference in genotype distribution and allele frequency of rs2267437 (XRCC6) was observed between the cases and controls. The CG carriers were at higher risk of ESCC (p = 0.001, odds ratio [OR] = 2.040, 95% confidence interval [95% CI], 1.323-3.147). G allele carriers were also associated with an increased ESCC risk (p = 0.003, OR = 1.868, 95% CI, 1.230-2.836). In the 2 polymorphisms of XRCC5, no significant difference was found between both groups in the distribution of either genotype or allelic frequency. But in the haplotypes established by the single nucleotide polymorphisms (SNPs) of XRCC5, the haplotype AT and CC separately increased by 4.28- and 2.31-fold the risk ratio of ESCC (p = 0.01, OR = 4.28, 95% CI, 1.40-13.05; p = 0.03, OR = 2.31, 95% CI, 1.11-4.80, respectively). In addition, gene-smoking or gene-drinking interactions, and their effect on the risk of ESCC were observed, but no significant gene-environment interaction was demonstrated.
  
  
  CONCLUSIONS
  In conclusion, both the CG carriers/G allele carriers of rs2267437 (XRCC6) and the haplotype AT/CC established by the SNPs of XRCC5 are associated with ESCC susceptibility.
authors.affiliation: Medical School, Shandong University, Jinan - PR China.
authors.forename: Kun
authors.initials: K
authors.lastname: Li
authors.forename: Xiuli
authors.initials: X
authors.lastname: Yin
authors.forename: Hongli
authors.initials: H
authors.lastname: Yang
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.forename: Jianjian
authors.initials: J
authors.lastname: Zhao
authors.forename: Changqing
authors.initials: C
authors.lastname: Xu
authors.forename: Hongwei
authors.initials: H
authors.lastname: Xu
mesh_terms: D000328:Adult; D000368:Aged; D034961:Antigens, Nuclear / Q000235:genetics*; D044466:Asian People / Q000235:genetics* / Q000706:statistics & numerical data; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology* / Q000235:genetics*; D002681:China / Q000453:epidemiology; D004265:DNA Helicases / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D000072200:Ku Autoantigen; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction / Q000379:methods; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D004265:DNA Helicases; C106893:XRCC5 protein, human; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen