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Common variation in the fibroblast growth factor receptor 2 (FGFR2) gene, hormone therapy use, and mammographic breast density

Du, Yan (2010) Common variation in the fibroblast growth factor receptor 2 (FGFR2) gene, hormone therapy use, and mammographic breast density. Master's Thesis, University of Pittsburgh. (Unpublished)

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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.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairDiergaarde, Brendadiergaardeb@upmc.eduBBD3
Committee MemberFeingold, Eleanorfeingold@pitt.eduFEINGOLD
Committee MemberWeissfeld, Joel
Date: 28 June 2010
Date Type: Completion
Defense Date: 29 March 2010
Approval Date: 28 June 2010
Submission Date: 4 April 2010
Access Restriction: 5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Human Genetics
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: FGFR2; mammographic breast density; polymorphisms
Other ID:, etd-04042010-093344
Date Deposited: 10 Nov 2011 19:34
Last Modified: 19 Dec 2016 14:35


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