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Breast cancer susceptibility associated with rs1219648 (fibroblast growth factor receptor 2) and postmenopausal hormone therapy use in a population-based United States study

Andersen, Shaneda Warren MS1,2; Trentham-Dietz, Amy PhD1,2; Figueroa, Jonine D. PhD3; Titus, Linda J. PhD4; Cai, Qiuyin MD, PhD5; Long, Jirong PhD5; Hampton, John M. MS1; Egan, Kathleen M. ScD6; Newcomb, Polly A. PhD1,7

doi: 10.1097/gme.0b013e318268ca46
Brief Report

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.

From the 1University of Wisconsin Carbone Cancer Center, Madison, WI; 2Department of Population Health Sciences, University of Wisconsin-Madison, Madison, WI; 3Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD; 4Norris Cotton Cancer Center, Dartmouth Medical School, Lebanon, NH; 5Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN; 6Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; and 7Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA.

Received May 10, 2012; revised and accepted July 9, 2012.

Funding/support: This work was supported by grants from the National Institutes of Health Cancer Institute (grants CA47147, CA47305, CA69664, and CA82004) and the Avon Foundation, and by the Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services. Genotyping assays were supported by the National Institutes of Health (grant R01CA124558) and performed at the Vanderbilt University Survey and Biospecimen Share Resource, which was supported, in part, by the Vanderbilt-Ingram Cancer Center (grant P30 CA68485).

Financial disclosure/conflicts of interest: None reported.

Address correspondence to: Shaneda Warren Andersen, MS, University of Wisconsin Carbone Cancer Center and Department of Population Health Sciences, University of Wisconsin-Madison, Room 307, 610 Walnut Street, Madison, WI 53726. E-mail:

© 2013 by The North American Menopause Society.