There is considerable evidence that excess adiposity is a risk factor for post-menopausal breast cancer, however the exact mechanism for this association is not known. While it has been hypothesized that the increase is the result of endogenous production of estrogen in adipose tissue, our understanding of the complex mechanism for this association is quite limited. Since the estrogen receptor plays a key role in mediating the biological impact of estrogen, inherited variants in the estrogen receptor-alpha {ESR1) gene are important candidates to study the association of estrogen, adiposity, and breast cancer risk. We propose a genetic/genomic epidemiology approach to test the central hypothesis that breast cancer risk is modulated by underlying single nucleotide and copy number variation in the ESR1 gene, and that excess adiposity modifies the association. We will conduct a genetic association study to evaluate the association of ESR1 genetic variation (single nucleotide and copy number variation) and breast cancer risk, and analyze the potential modifying effect of adiposity. We will also examine the association of ESR1 variants and adiposity with tumor characteristics, and investigate whether adiposity is related to differences in ESR1 copy number between germline DNA and breast cancer tumor DNA samples. The main objectives of the Career Development Award include gaining experience in the genetic epidemiology of breast cancer, becoming an expert in the characteristics and measurement of copy number variation in the genome and how to integrate the study of this newly recognized type of genetic variation into epidemiologic studies, while simultaneously conducting specific hypothesis-driven analyses.
The specific aims will be accomplished using an existing case-control study of breast cancer in Western New York. The applicant, who is a trained epidemiologist, will utilize the skills attained during her postdoctoral training in genetic epidemiology to become an expert in cancer biology with a focus on the contributions of estrogen and adiposity, evaluation of different types of genomic variation and the relation with cancer and will obtain further training in cancer genetics/genomics.

Public Health Relevance

The increasing prevalence of adiposity in the U.S. and the consistent relationship of adiposity and post- menopausal breast cancer warrant further study of how adiposity, estrogen, and breast cancer are related. The proposal is significant because we will shed light on the complex interaction of estrogen, adiposity, and breast cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Academic/Teacher Award (ATA) (K07)
Project #
5K07CA136969-04
Application #
8314136
Study Section
Subcommittee G - Education (NCI)
Program Officer
Perkins, Susan N
Project Start
2009-09-17
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
4
Fiscal Year
2012
Total Cost
$166,515
Indirect Cost
$12,334
Name
State University of New York at Buffalo
Department
Public Health & Prev Medicine
Type
Schools of Allied Health Profes
DUNS #
038633251
City
Buffalo
State
NY
Country
United States
Zip Code
14260
Ochs-Balcom, Heather M; Sun, Xiangqing; Chen, Yanwen et al. (2015) Putative linkage signals identified for breast cancer in African American families. Cancer Epidemiol Biomarkers Prev 24:442-7
Ochs-Balcom, Heather M; Jandorf, Lina; Wang, Youjin et al. (2015) "It takes a village": multilevel approaches to recruit African Americans and their families for genetic research. J Community Genet 6:39-45
Ochs-Balcom, Heather M; Vaughn, Caila B; Nie, Jing et al. (2014) Racial differences in the association of insulin-like growth factor pathway and colorectal adenoma risk. Cancer Causes Control 25:161-70
Monda, Keri L; Chen, Gary K; Taylor, Kira C et al. (2013) A meta-analysis identifies new loci associated with body mass index in individuals of African ancestry. Nat Genet 45:690-6
Ricks-Santi, Luisel J; Nie, Jing; Marian, Catalin et al. (2013) BRCA1 polymorphisms and breast cancer epidemiology in the Western New York exposures and breast cancer (WEB) study. Genet Epidemiol 37:504-11
Qi, Lihong; Nassir, Rami; Kosoy, Roman et al. (2013) Relationship between hysterectomy and admixture in African American women. Am J Obstet Gynecol 208:279.e1-7
Vaughn, Caila B; Ochs-Balcom, Heather M; Nie, Jing et al. (2013) No Association between Circulating Levels and Genetic Variants of IL-6 and TNF-* and Colon Adenoma. Gastroenterology Res 6:
Rohan, Thomas E; Heo, Moonseong; Choi, Lydia et al. (2013) Body fat and breast cancer risk in postmenopausal women: a longitudinal study. J Cancer Epidemiol 2013:754815
Ochs-Balcom, Heather M; Preus, Leah; Wactawski-Wende, Jean et al. (2013) Association of DXA-derived bone mineral density and fat mass with African ancestry. J Clin Endocrinol Metab 98:E713-7
Guo, Yiran; Lanktree, Matthew B; Taylor, Kira C et al. (2013) Gene-centric meta-analyses of 108 912 individuals confirm known body mass index loci and reveal three novel signals. Hum Mol Genet 22:184-201

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