title: Variants of estrogen receptor alpha and beta genes modify the severity of sporadic breast cancer.
abstract: BACKGROUND
  Reproductive factors pose a risk for sporadic breast cancer (BC) development owing to the lifetime exposure to estrogen, a hormone responsible for cell proliferation in the breast. Because variants of the estrogen receptor (ER) alpha and beta genes have been associated with BC risk in numerous populations, the objective of the study was to determine whether the risk and severity of sporadic BC was associated with the rs2228480 (ESR1) and rs4986938 (ESR2) variants in a Brazilian population.
  
  
  METHODS
  A total of 253 DNA samples from sporadic BC patients and 257 DNA samples from healthy controls were studied. The samples were genotyped by PCR-RFLP. Epidemiological, clinical, and reproductive factors were analyzed. Statistical tests conducted included the χ2test, Fisher's exact test, and Mann-Whitney and Kruskal-Wallis tests or their parametric equivalents.
  
  
  RESULTS
  There was a high frequency of the rs2228480*GG genotype among the ER-positive tumors (OR=2.13; 95% CI=1.189-3.816) and it showed minor association with clinical stage 0 (OR=0.324; 95% CI=0.116-0.904). The rs2228480*GA genotype was associated with minor ER expression, whereas rs2228480*GG was associated with high expression of the progesterone receptor (PR). The frequency of rs4986938*GA was high among women who breastfed (OR=2.11; 95% CI=1.203-3.702), and it showed high association with clinical stage 0 (OR=4.383; 95% CI=1.606-11.96) whereas it had minor association with systemic arterial hypertension (OR=0.53; 95% CI=0.319-0.880). The rs2228480*GG/rs4986938*GG haplotype occurred at a low frequency among women who breastfed (OR=0.525; 95% CI=0.298-0.924) but it was associated with a high expression of PR.
  
  
  CONCLUSIONS
  The rs2228480 and rs4986938 variants did not alter sporadic BC risk, but they did modulate the BC severity.
authors.affiliation: Department of Medical Genetics, Faculty of Medical Sciences, State University of Campinas - Unicamp, Brazil. Electronic address: luciana_mrezende@hotmail.com.
authors.forename: Luciana Montes
authors.initials: LM
authors.lastname: Rezende
authors.affiliation: Department of Medical Genetics, Faculty of Medical Sciences, State University of Campinas - Unicamp, Brazil; Department of Pediatrics, Faculty of Medical Sciences, State University of Campinas - Unicamp, Brazil. Electronic address: fernandolimamarson@hotmail.com.
authors.forename: Fernando Augusto Lima
authors.initials: FA
authors.lastname: Marson
authors.affiliation: Department of Medical Clinics, Faculty of Medical Sciences, State University of Campinas - Unicamp, Brazil. Electronic address: carmenl@fcm.unicamp.br.
authors.forename: Carmen Sílvia Passos
authors.initials: CS
authors.lastname: Lima
authors.affiliation: Department of Medical Genetics, Faculty of Medical Sciences, State University of Campinas - Unicamp, Brazil. Electronic address: bertuzzo@unicamp.br.
authors.forename: Carmen Sílvia
authors.initials: CS
authors.lastname: Bertuzzo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001938:Brazil; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D047628:Estrogen Receptor alpha / Q000235:genetics*; D047629:Estrogen Receptor beta / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012720:Severity of Illness Index
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta
keywords: ESR1; ESR2; Modifier gene; Neoplasia; Risk factor