title: Combined effect of CYP1B1, COMT, GSTP1, and MnSOD genotypes and risk of postmenopausal breast cancer.
abstract: OBJECTIVE
  Estrogen plays a key role in breast cancer development and functionally relevant genetic variants within the estrogen metabolic pathway are prime candidates for a possible association with breast cancer risk. We investigated the independent and the combined effects of commonly occurring polymorphisms in four genes encoding key proteins of estrogen metabolic pathway on their potential contribution to breast cancer risk.
  
  
  METHODS
  We studied 530 breast cancer cases and 270 controls of the same age and ethnicity participating in a case-control study of postmenopausal women. Genotyping was conducted for CYP1B1 (rs1056836), COMT (rs4680), GSTP1 (rs1695), and MnSOD (rs4880) polymorphisms by polymerase chain reaction based restriction fragment length polymorphism and TaqMan allelic discrimination method. Adjusted ORs and 95% CIs were calculated using logistic regression.
  
  
  RESULTS
  None of the 4 genetic variants examined contributed to breast cancer risk individually. When the combined effects of the risk genotypes were investigated, significant associations were observed among women with two high-risk genotypes in CYP1B1 and COMT (OR, 2.0; 95% CI, 1.1 to 3.5) and two high-risk genotypes in COMT and MnSOD (OR, 2.0; 95% CI, 1.0 to 3.8), compared to those with low-risk genotypes.
  
  
  CONCLUSIONS
  Our results suggest that individual susceptibility to breast cancer incidence may be increased by combined effects of the high-risk genotypes in CYP1B1, COMT, and MnSOD estrogen metabolic genes.
authors.affiliation: Institute of Medical Genetics, Department of Obstetrics and Gynecology, University Medical Center Ljubljana, Slajmerjeva 3, 1000 Ljubljana, Slovenia.
authors.forename: Jasmina-Ziva
authors.initials: JZ
authors.lastname: Cerne
authors.forename: Maja
authors.initials: M
authors.lastname: Pohar-Perme
authors.forename: Srdjan
authors.initials: S
authors.lastname: Novakovic
authors.forename: Snjezana
authors.initials: S
authors.lastname: Frkovic-Grazio
authors.forename: Vida
authors.initials: V
authors.lastname: Stegel
authors.forename: Ksenija
authors.initials: K
authors.lastname: Gersak