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.
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.
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
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.