title: SNP-SNP interactions between DNA repair genes were associated with breast cancer risk in a Korean population.
abstract: BACKGROUND
  Single nucleotide polymorphisms (SNPs) in nucleotide excision repair (NER) pathway genes may modulate DNA repair capacity and increase susceptibility to breast cancer (BC). A case-control study was conducted by evaluating genes involved in DNA repair to identify polymorphisms associated with BC.
  
  
  METHODS
  The 384 SNPs of 38 candidate genes were genotyped using the Illumina GoldenGate method. Genotypes were determined in a case-control study that consisted of 346 BC patients and 361 controls. Odds ratios and 95% confidence intervals were computed using logistic regression models. Multiple logistic regression models adjusted for age, family history of BC, and body mass index were used.
  
  
  RESULTS
  Gene-gene interaction analysis among the DNA repair pathway genes showed significant effects on BC risk. ERCC2 rs50872 (TC genotype) in combination with XPA rs2808668 (TC genotype) and rs1800975 (AG genotype) was strongly associated with an increased risk of BC (P = .0004 and .0002, P(Bonferroni) = .023 and .014, respectively). Moreover, the T-G (including rs2808668 and rs1800975) haplotype in XPA combined with the ERCC2 T allele in rs50872 carriers was also associated with additive risk effect of BC (odds ratios: 2.58, 2.62, and 3.49, respectively).
  
  
  CONCLUSIONS
  Genetic variation in DNA repair genes involved in NER mechanisms increased the risk of BC development. These results suggested that a stronger combined effect of SNPs via gene-gene interaction may help to predict BC risk.
authors.affiliation: Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Wonshik
authors.initials: W
authors.lastname: Han
authors.forename: Kyoung-Yeon
authors.initials: KY
authors.lastname: Kim
authors.forename: Song-Ju
authors.initials: SJ
authors.lastname: Yang
authors.forename: Dong-Young
authors.initials: DY
authors.lastname: Noh
authors.forename: Daehee
authors.initials: D
authors.lastname: Kang
authors.forename: KyuBum
authors.initials: K
authors.lastname: Kwack
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D004247:DNA / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics* / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D056910:Republic of Korea / Q000453:epidemiology; D012307:Risk Factors; D051760:Xeroderma Pigmentosum Group A Protein / Q000235:genetics / Q000378:metabolism; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C497314:XPA protein, human; D051760:Xeroderma Pigmentosum Group A Protein; D004247:DNA; C071447:ERCC1 protein, human; D004720:Endonucleases; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human; D045643:DNA Repair Enzymes