title: Oxidative stress in susceptibility to breast cancer: study in Spanish population.
abstract: BACKGROUND
  Alterations in the redox balance are involved in the origin, promotion and progression of cancer. Inter-individual differences in the oxidative stress regulation can explain a part of the variability in cancer susceptibility.The aim of this study was to evaluate if polymorphisms in genes codifying for the different systems involved in oxidative stress levels can have a role in susceptibility to breast cancer.
  
  
  METHODS
  We have analyzed 76 single base polymorphisms located in 27 genes involved in oxidative stress regulation by SNPlex technology. First, we have tested all the selected SNPs in 493 breast cancer patients and 683 controls and we have replicated the significant results in a second independent set of samples (430 patients and 803 controls). Gene-gene interactions were performed by the multifactor dimensionality reduction approach.
  
  
  RESULTS
  Six polymorphisms rs1052133 (OGG1), rs406113 and rs974334 (GPX6), rs2284659 (SOD3), rs4135225 (TXN) and rs207454 (XDH) were significant in the global analysis. The gene-gene interactions demonstrated a significant four-variant interaction among rs406113 (GPX6), rs974334 (GPX6), rs105213 (OGG1) and rs2284659 (SOD3) (p-value = 0.0008) with high-risk genotype combination showing increased risk for breast cancer (OR = 1.75 [95% CI; 1.26-2.44]).
  
  
  CONCLUSIONS
  The results of this study indicate that different genotypes in genes of the oxidant/antioxidant pathway could affect the susceptibility to breast cancer. Furthermore, our study highlighted the importance of the analysis of the epistatic interactions to define with more accuracy the influence of genetic variants in susceptibility to breast cancer.
authors.forename: Patricia
authors.initials: P
authors.lastname: Rodrigues
authors.forename: Griselda
authors.initials: G
authors.lastname: de Marco
authors.forename: Jessica
authors.initials: J
authors.lastname: Furriol
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Mansego
authors.forename: Mónica
authors.initials: M
authors.lastname: Pineda-Alonso
authors.forename: Anna
authors.initials: A
authors.lastname: Gonzalez-Neira
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Martin-Escudero
authors.forename: Javier
authors.initials: J
authors.lastname: Benitez
authors.forename: Ana
authors.initials: A
authors.lastname: Lluch
authors.forename: Felipe J
authors.initials: FJ
authors.lastname: Chaves
authors.affiliation: INCLIVA Biomedical Research Institute, Valencia, Spain. pilar.eroles@uv.es.
authors.forename: Pilar
authors.initials: P
authors.lastname: Eroles
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000209:etiology*; D016022:Case-Control Studies; D002874:Chromosome Mapping; D030541:Databases, Genetic; D004198:Disease Susceptibility; D004843:Epistasis, Genetic; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D018384:Oxidative Stress / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011159:Population Surveillance; D013030:Spain / Q000453:epidemiology; D044465:White People / Q000235:genetics; D055815:Young Adult