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 #
5K07CA136969-03
Application #
8127754
Study Section
Subcommittee G - Education (NCI)
Program Officer
Perkins, Susan N
Project Start
2009-09-17
Project End
2014-08-31
Budget Start
2011-09-01
Budget End
2012-08-31
Support Year
3
Fiscal Year
2011
Total Cost
$162,751
Indirect Cost
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
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Soucise, Allison; Vaughn, Caila; Thompson, Cheryl L et al. (2017) Sleep quality, duration, and breast cancer aggressiveness. Breast Cancer Res Treat 164:169-178
Ochs-Balcom, Heather M; Marian, Catalin; Nie, Jing et al. (2015) Adiposity is associated with p53 gene mutations in breast cancer. Breast Cancer Res Treat 153:635-45
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
Neuhouser, Marian L; Aragaki, Aaron K; Prentice, Ross L et al. (2015) Overweight, Obesity, and Postmenopausal Invasive Breast Cancer Risk: A Secondary Analysis of the Women's Health Initiative Randomized Clinical Trials. JAMA Oncol 1:611-21
Parekh, Niyati; Guffanti, Guia; Lin, Yong et al. (2015) Insulin receptor variants and obesity-related cancers in the Framingham Heart Study. Cancer Causes Control 26:1189-95
Ochs-Balcom, Heather M; Phillips, Lynette S; Nichols, Hazel B et al. (2015) Building a funded research program in cancer health disparities: considerations for young investigators. Cancer Epidemiol Biomarkers Prev 24:882-5
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; 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
Coram, Marc A; Duan, Qing; Hoffmann, Thomas J et al. (2013) Genome-wide characterization of shared and distinct genetic components that influence blood lipid levels in ethnically diverse human populations. Am J Hum Genet 92:904-16

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