title: The estrogen receptor alpha gene and breast cancer risk (The Netherlands).
abstract: OBJECTIVE
  In this study we aimed to investigate whether the PvuII, XbaI and B-variant polymorphisms in the estrogen receptor alpha gene (ER-alpha) are associated with an increased risk of breast cancer in postmenopausal women, and whether the effect of high estradiol (E2) levels on breast cancer risk is altered by these polymorphisms. The selection of these polymorphisms was based on previously published associations with osteoporosis and spontaneous abortions.
  
  
  METHODS
  The effect of the three polymorphisms on breast cancer risk was studied using a case-cohort design nested within a large population-based cohort study (n = 9349) in the Netherlands (the DOM-cohort). In total 380 incident breast cancer cases and a subcohort of 422 women were genotyped by RFLP or ASO hybridization methods.
  
  
  RESULTS
  Women with the PvuII pp genotype had a 1.5 times non significant increased risk of breast cancer (95% CI: 0.94-2.42; p(trend) = 0.09) compared to women with the PP genotype. The Pp or pp genotype in combination with high E2 levels raised breast cancer risk significantly when compared to women with low E2 levels and the PP genotype (RR=2.26; 95% CI: 1.24-4.13). This interaction was statistically significant on the multiplicative scale (p = 0.01). The XbaI genotype (RR(xx versus XX) = 1.19; 95% CI: 0.73-1.95) and the B' allele (RR(BB'+B'B' versus BB) = 0.87; 95% CI: 0.56-1.33) were not associated with breast cancer risk.
  
  
  CONCLUSIONS
  The results of this study suggest that the PvuII polymorphism in the ER-alpha, or another mutation in linkage disequilibrium with PvuII, in combination with high E2 levels increases breast cancer risk in postmenopausal women.
authors.affiliation: Julius Center for Health Sciences and Primary Care, UMC Utrecht, Room St. 6.131, PO Box 85500, 3508, GA Utrecht, The Netherlands.
authors.forename: N Charlotte
authors.initials: NC
authors.lastname: Onland-Moret
authors.forename: Carla H
authors.initials: CH
authors.lastname: van Gils
authors.forename: Mark
authors.initials: M
authors.lastname: Roest
authors.forename: Diederick E
authors.initials: DE
authors.lastname: Grobbee
authors.forename: Petra H M
authors.initials: PH
authors.lastname: Peeters
mesh_terms: D000368:Aged; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000652:urine; D015331:Cohort Studies; D004958:Estradiol / Q000652:urine; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D011110:Polymorphism, Genetic; D017698:Postmenopause; D012307:Risk Factors
chemical_list: D047628:Estrogen Receptor alpha; D004958:Estradiol