title: Breast cancer susceptibility associated with rs1219648 (fibroblast growth factor receptor 2) and postmenopausal hormone therapy use in a population-based United States study.
abstract: OBJECTIVE
  Genomewide association studies have consistently found variants in fibroblast growth factor receptor 2 (FGFR2) to be associated with breast cancer. Recent reports suggest that postmenopausal hormone therapy (HT) use may modify the association between single nucleotide polymorphisms (SNPs) in FGFR2 and breast cancer risk. We assessed the hypothesis that the association between rs1219648 (FGFR2) SNP and breast cancer risk is modified by postmenopausal HT use in a population-based case-control study.
  
  
  METHODS
  We evaluated rs1219648 SNP for an association with breast cancer risk using data obtained from 869 postmenopausal breast cancer cases diagnosed between 1995 and 2000 and from 808 postmenopausal community controls who participated in a study conducted in three US states. Detailed postmenopausal HT information was collected through a structured telephone interview, and DNA samples were collected by mail using an established mouthwash protocol. Odds ratios and 95% confidence intervals (CIs) were calculated using logistic regression models adjusted for age and state of residence.
  
  
  RESULTS
  We observed a significant association between rs1219648 and breast cancer risk (per-allele odds ratio, 1.22; 95% CI, 1.06-1.41; P = 0.007), which did not vary significantly by ever use of estrogen plus progestogen therapy (interaction P = 0.48). There was stronger evidence of an interaction between ever use of estrogen-only HT and increasing number of rs1219648 risk alleles to increase breast cancer risk (interaction P = 0.08).
  
  
  CONCLUSIONS
  Our results are consistent with a risk association with FGFR2 but provide limited support for interaction with HT use. The study raises the possibility that the FGFR2 rs1219648 variant is more strongly associated with risk in estrogen-only hormone users, although this observation needs to be examined in larger studies.
authors: University of Wisconsin Carbone Cancer Center, Madison, WI, USA. snandersen@wisc.edu
authors: Shaneda Warren
authors: SW
authors: Andersen
authors: Amy
authors: A
authors: Trentham-Dietz
authors: Jonine D
authors: JD
authors: Figueroa
authors: Linda J
authors: LJ
authors: Titus
authors: Qiuyin
authors: Q
authors: Cai
authors: Jirong
authors: J
authors: Long
authors: John M
authors: JM
authors: Hampton
authors: Kathleen M
authors: KM
authors: Egan
authors: Polly A
authors: PA
authors: Newcomb
mesh_terms: D000483:Alleles; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D004247:DNA / Q000032:analysis; D015914:Estrogen Replacement Therapy / Q000009:adverse effects / Q000379:methods; D004967:Estrogens / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017698:Postmenopause; D011372:Progestins / Q000008:administration & dosage; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics*; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
chemical_list: D004967:Estrogens; D011372:Progestins; D004247:DNA; C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2