Objectives: Mammographic breast density (MBD) is a strong risk factor for breast cancer. It has been hypothesized that breast cancer susceptibility loci may also be associated with breast density. Recently, two genome-wide association studies identified a single-nucleotide polymorphism (SNP), rs2981582, in intron 2 of the FGFR2 gene to be associated with increased breast cancer risk. Further research revealed that intron 2 of FGFR2 contains estrogen receptor transcription factor binding sites. We examined associations of four FGFR2 SNPs (rs2981582, rs3750817, rs17542768 and rs1219643), hormone therapy (HT) use, and their interactions with MBD.
Methods: We conducted a cross-sectional analysis using a subset of the Mammograms and Masses Study population. Subjects were 370 healthy postmenopausal Caucasian women. General linear models adjusted for covariates were used to evaluate the associations.
Results: Overall, no statistically significant associations were observed between the four SNPs in FGFR2 and MBD. Duration of estrogen plus progestin use, but not duration of estrogen use, and HT status were statistically significantly associated with MBD in our study population. No statistically significant interactions between genotypes and HT use were observed.
Conclusions: Our results suggest that the effects of the four evaluated FGFR2 polymorphisms on breast cancer risk are not mediated through MBD, and that the polymorphisms do not modify the effect of HT use on MBD.
Implications for public health: Breast cancer is the most common cancer in women in the U.S. Identification of genes that influence MBD may provide insight into the biology of breast density and its effect on breast cancer, eventually leading to more effective prevention and treatment.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-04042010-093344 |
| Date | 28 June 2010 |
| Creators | Du, Yan |
| Contributors | Eleanor Feingold, PhD, Brenda Diergaarde, PhD, Joel L. Weissfeld, MD, MPH |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-04042010-093344/ |
| Rights | restricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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