title: Polymorphisms of the NER pathway genes, ERCC1 and XPD are associated with esophageal adenocarcinoma risk.
abstract: OBJECTIVE
  Functional variation in DNA repair capacity through single nucleotide polymorphisms (SNPs) of key repair genes is associated with a higher risk of developing various types of cancer. Studies have focused on the nucleotide excision repair (NER) and base excision repair (BER) pathways. We investigated whether variant alleles in seven SNPs within these pathways increased the risk of esophageal adenocarcinoma.
  
  
  METHODS
  DNA was extracted from prospectively collected blood specimens. The samples were genotyped for SNPs in NER genes (XPD Lys751Gln, XPD Asp312Asn, ERCC1 8092C/A, and ERCC1 118C/T), and BER genes (XRCC1 Arg399Gln, APE1 Asp148Glu, and hOGG1 Ser326Cys). The presence of variant alleles was correlated with risk of esophageal adenocarcinoma both individually and jointly.
  
  
  RESULTS
  Variant alleles in NER SNPs XPD Lys751Gln (AOR = 1.50, 95% CI 1.1-2.0), ERCC1 8092 C/A (AOR = 1.44, 95% CI 1.1-1.9), and ERCC1 118C/T (AOR = 1.42, 95% CI 1.0-1.9) were individually associated with esophageal adenocarcinoma risk. An increasing number of variant alleles in NER SNPs showed a significant trend with esophageal adenocarcinoma risk (p = 0.007).
  
  
  CONCLUSIONS
  The presence of variant alleles in NER genes increases risk of esophageal adenocarcinoma. There is evidence of an additive role for SNPs along a common DNA repair pathway. Future larger studies of esophageal adenocarcinoma etiology should evaluate entire biological pathways.
authors.affiliation: Department of Applied Molecular Oncology, Ontario Cancer Institute, Princess Margaret Hospital, Toronto, ON, Canada.
authors.forename: Darren
authors.initials: D
authors.lastname: Tse
authors.forename: Rihong
authors.initials: R
authors.lastname: Zhai
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Heist
authors.forename: Kofi
authors.initials: K
authors.lastname: Asomaning
authors.forename: Li
authors.initials: L
authors.lastname: Su
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Lynch
authors.forename: John C
authors.initials: JC
authors.lastname: Wain
authors.forename: David C
authors.initials: DC
authors.lastname: Christiani
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Liu
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D004720:Endonucleases / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics*; D005260:Female; D006801:Humans; D007407:Interviews as Topic; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D011795:Surveys and Questionnaires; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; C071447:ERCC1 protein, human; D004720:Endonucleases; D051759:Xeroderma Pigmentosum Group D Protein