title: Estrogen receptor polymorphism at codon 325 and risk of breast cancer in women before age forty.
abstract: BACKGROUND
  The estrogen receptor (ER) protein is believed to play a role in the development and progression of breast cancer. In a previously published U.S. clinic-based study, a polymorphism in the ER gene (codon 325, CCC --> CCG) was found to be more common in 34 case subjects with a family history of breast cancer than in 154 case subjects without such a history (mean allele frequencies +/- standard error = 0.28+/-0.05 versus 0.11+/-0.02; P<.001). To determine whether this polymorphism is a risk factor for early-onset breast cancer, we conducted a population-based, case-control-family study in Australia.
  
  
  METHODS
  Case subjects under the age of 40 years with a first primary breast cancer and control subjects, frequency-matched to the case subjects on the basis of age, and their relatives were interviewed to assess the family history of breast cancer. Polymorphism status of the ER gene was determined for 388 case subjects and 294 control subjects. All statistical tests were two-tailed.
  
  
  RESULTS
  There was no association between ER gene polymorphism status and breast cancer, before or after adjustment for risk factors. There was no difference in allele frequencies between case subjects and control subjects (0.232+/-0.015 versus 0.209+/-0.017; P = .4) or between women with and without a family history of breast cancer (P = .3), irrespective of case-control status. The findings were not altered when different definitions of family history of breast cancer were used and when allele frequencies were adjusted for residence and country of birth.
  
  
  CONCLUSIONS
  We found no evidence that the ER codon 325 polymorphism is associated with breast cancer before the age of 40 years or with a family history of breast cancer, despite ample power to detect effects half the magnitude of those previously reported.
authors.affiliation: Department of Pathology and Research, Peter MacCallum Cancer Institute, Melbourne, Australia. m.southey@pmci.unimelb.edu.au
authors.forename: M C
authors.initials: MC
authors.lastname: Southey
authors.forename: L E
authors.initials: LE
authors.lastname: Batten
authors.forename: M R
authors.initials: MR
authors.lastname: McCredie
authors.forename: G G
authors.initials: GG
authors.lastname: Giles
authors.forename: G
authors.initials: G
authors.lastname: Dite
authors.forename: J L
authors.initials: JL
authors.lastname: Hopper
authors.forename: D J
authors.initials: DJ
authors.lastname: Venter
mesh_terms: D000328:Adult; D000483:Alleles; D001315:Australia; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D003062:Codon / Q000235:genetics*; D017931:DNA Primers; D005260:Female; D006801:Humans; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011960:Receptors, Estrogen / Q000235:genetics*
chemical_list: D003062:Codon; D017931:DNA Primers; D011960:Receptors, Estrogen