title: Gene x Gene interaction between MnSOD and GPX-1 and breast cancer risk: a nested case-control study.
abstract: BACKGROUND
  Germ-line mutations in genes such as BRCA1, BRCA2, and ATM can cause a substantial increase in risk of breast cancer. However, these mutations are rare in the general population, and account for little of the incidence of sporadic breast cancer in the general population. Therefore, research has been focused on examining associations between common polymorphisms and breast cancer risk. To date, few associations have been described. This has led to the hypothesis that breast cancer is a complex disease, whereby a constellation of very low penetrance alleles need to be carried to present a risk phenotype. Polymorphisms in the manganese superoxide dismutase (MnSOD) and glutathione peroxidase (GPX-1) genes have been proposed as low penetrance alleles, and have not been clearly associated with breast cancer. We investigated whether variants at both polymorphisms, while not independently associated with breast cancer risk, could influence breast cancer risk when considered together.
  
  
  METHODS
  A case-control study nested within the Nurses' Health Study was performed comparing 1262 women diagnosed with breast cancer to 1533 disease free women. The MnSOD (Val16Ala, rs1799725) and GPX-1 (Pro198Leu, rs1050450) were genotyped via TaqMan assay. Disease risk was evaluated using logistic regression.
  
  
  RESULTS
  While neither allele alone shows any change in breast cancer risk, an increase in the risk of breast cancer (OR 1.87, 95% CI 1.09 - 3.19) is observed in individuals who carry both the Ala16Ala genotype of MnSOD and the Leu198Leu genotype of GPX-1.
  
  
  CONCLUSIONS
  Polymorphisms in the GPX-1 and MnSOD genes are associated with an increased risk of breast cancer.
authors.affiliation: Program in Molecular and Genetic Epidemiology, Epidemiology Department, Harvard School of Public Health, 677 Huntington Ave., Boston, MA 02115, USA. dcox@hsph.harvard.edu
authors.forename: David G
authors.initials: DG
authors.lastname: Cox
authors.forename: Rulla M
authors.initials: RM
authors.lastname: Tamimi
authors.forename: David J
authors.initials: DJ
authors.lastname: Hunter
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018095:Germ-Line Mutation; D005979:Glutathione Peroxidase / Q000235:genetics*; D006801:Humans; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic; D012306:Risk; D013482:Superoxide Dismutase / Q000235:genetics*; D000094765:Glutathione Peroxidase GPX1
chemical_list: D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human