title: Oestrogen receptor alpha gene haplotype and postmenopausal breast cancer risk: a case control study.
abstract: BACKGROUND
  Oestrogen receptor alpha, which mediates the effect of oestrogen in target tissues, is genetically polymorphic. Because breast cancer development is dependent on oestrogenic influence, we have investigated whether polymorphisms in the oestrogen receptor alpha gene (ESR1) are associated with breast cancer risk.
  
  
  METHODS
  We genotyped breast cancer cases and age-matched population controls for one microsatellite marker and four single-nucleotide polymorphisms (SNPs) in ESR1. The numbers of genotyped cases and controls for each marker were as follows: TAn, 1514 cases and 1514 controls; c.454-397C --> T, 1557 cases and 1512 controls; c.454-351A --> G, 1556 cases and 1512 controls; c.729C --> T, 1562 cases and 1513 controls; c.975C --> G, 1562 cases and 1513 controls. Using logistic regression models, we calculated odds ratios (ORs) and 95% confidence intervals (CIs). Haplotype effects were estimated in an exploratory analysis, using expectation-maximisation algorithms for case-control study data.
  
  
  RESULTS
  There were no compelling associations between single polymorphic loci and breast cancer risk. In haplotype analyses, a common haplotype of the c.454-351A --> G or c.454-397C --> T and c.975C --> G SNPs appeared to be associated with an increased risk for ductal breast cancer: one copy of the c.454-351A --> G and c.975C --> G haplotype entailed an OR of 1.19 (95% CI 1.06-1.33) and two copies with an OR of 1.42 (95% CI 1.15-1.77), compared with no copies, under a model of multiplicative penetrance. The association with the c.454-397C --> T and c.975C --> G haplotypes was similar. Our data indicated that these haplotypes were more influential in women with a high body mass index. Adjustment for multiple comparisons rendered the associations statistically non-significant.
  
  
  CONCLUSIONS
  We found suggestions of an association between common haplotypes in ESR1 and the risk for ductal breast cancer that is stronger in heavy women.
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. sara.wedren@meb.ki.se
authors.forename: Sara
authors.initials: S
authors.lastname: Wedrén
authors.forename: Lovisa
authors.initials: L
authors.lastname: Lovmar
authors.forename: Keith
authors.initials: K
authors.lastname: Humphreys
authors.forename: Cecilia
authors.initials: C
authors.lastname: Magnusson
authors.forename: Håkan
authors.initials: H
authors.lastname: Melhus
authors.forename: Ann-Christine
authors.initials: AC
authors.lastname: Syvänen
authors.forename: Andreas
authors.initials: A
authors.lastname: Kindmark
authors.forename: Ulf
authors.initials: U
authors.lastname: Landegren
authors.forename: Maria Lagerström
authors.initials: ML
authors.lastname: Fermér
authors.forename: Fredrik
authors.initials: F
authors.lastname: Stiger
authors.forename: Ingemar
authors.initials: I
authors.lastname: Persson
authors.forename: John
authors.initials: J
authors.lastname: Baron
authors.forename: Elisabete
authors.initials: E
authors.lastname: Weiderpass
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D047628:Estrogen Receptor alpha; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics*
chemical_list: D047628:Estrogen Receptor alpha; D005819:Genetic Markers; D011960:Receptors, Estrogen