title: Genetic polymorphism of ESR1 rs2881766 increases breast cancer risk in Korean women.
abstract: OBJECTIVE
  We performed a case-control study to evaluate the association of genetic polymorphisms of estrogen-metabolizing enzyme genes and estrogen receptor genes with breast cancer risk according to age group and subtypes in Korean women.
  
  
  METHODS
  Breast cancer patients (n = 830) and the hospital healthy controls (n = 390) with both clinical information and SNP data were included in the study. Age was divided into three groups: premenopausal under 35 years (n = 64), premenopausal over 35 years (n = 456), and postmenopausal women (n = 310), respectively. Tumor subtype was classified into four subtypes: luminal A, luminal B, HER2-overexpressing, and triple-negative, respectively. Genotyping of the selected SNPs in ESR1, ESR2, CYP1A1, CYP1B1, and COMT was conducted using the VeraCode Golden Gate Genotyping Assay Technology. Multiple logistic regression models (dominant, recessive, and additive) were applied to determine the odds ratio, 95% confidence interval, and p value.
  
  
  RESULTS
  ESR1, rs2881766, rs2077647, rs926778, and rs2273206 polymorphisms increased breast cancer risk, and rs3798377 decreased the risk in overall patients. The association between SNP genotype and breast cancer risk was varied according to age groups and tumor subtypes. For age subgroups, rs2881766 increased breast cancer risk in the all three age groups, and rs926778 increased the risk in premenopausal over 35 years women and in postmenopausal women. For the tumor subtypes, rs2881766 increased breast cancer risk manly in luminal A, HER2-overexpressing, and triple-negative subtypes except for luminal B subtype, and rs926778 increased the risk in luminal A and triple-negative subtypes. Rs3798577 decreased the risk in luminal B and triple-negative subtypes.
  
  
  CONCLUSIONS
  The results showed that ESR1 rs2881766 polymorphism increased breast cancer risk and rs3798377 decreased the risk in Korean women. Because of wide variation of the association between SNP genotype and breast cancer risk according to age group and tumor subtypes, further studies such as a large-scale cohort study need for validation and test of biologic significance.
authors.affiliation: Department of Surgery, College of Medicine, Asan Medical Center, University of Ulsan, Seoul, Korea.
authors.forename: Byung Ho
authors.initials: BH
authors.lastname: Son
authors.forename: Mi Kyung
authors.initials: MK
authors.lastname: Kim
authors.forename: Young Mi
authors.initials: YM
authors.lastname: Yun
authors.forename: Hee Jeong
authors.initials: HJ
authors.lastname: Kim
authors.forename: Jong Han
authors.initials: JH
authors.lastname: Yu
authors.forename: Beom Seok
authors.initials: BS
authors.lastname: Ko
authors.forename: Hanna
authors.initials: H
authors.lastname: Kim
authors.forename: Sei Hyun
authors.initials: SH
authors.lastname: Ahn
mesh_terms: D000328:Adult; D044466:Asian People; D001943:Breast Neoplasms / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause / Q000208:ethnology / Q000235:genetics; D017697:Premenopause / Q000208:ethnology / Q000235:genetics; D056910:Republic of Korea; D012307:Risk Factors
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha