The incidence of breast and endometrial cancers varies almost three-fold between non-Hispanic white populations and Native American and Hispanic populations living in the 4-Corners area of the United States (Arizona, New Mexico, Colorado, and Utah). Interestingly, although American Indian and Hispanic women have higher prevalences of many risk factors for breast and endometrial cancer identified in non-Hispanic white women (e.g., obesity, low levels of vigorous physical activity, low intakes of fruits and vegetables, high rates of insulin resistance) they have lower cancer incidence rates. In this study the investigators focus on the metabolic factors of obesity/weight changes and indicators of insulin status as they relate to breast and endometrial cancers. Obesity is associated both with estrogen and insulin by two interrelated disease pathways. Insulin may influence cancer risk directly through its effects on insulin-like growth factor (IGF) and its binding proteins (IGFBPs) and well as indirectly through its effect on estrogen levels. The investigators propose focusing on the insulin pathway because of the high levels of insulin pathway dysfunction in this population. A multi-center case-control study is proposed that targets women living in the 4-Corners area; the study will consist of a 2.5 hour in-person interview and a blood draw. Over a three-year case ascertainment period, the study will enroll 3000 breast cancer cases, 450 endometrial cancer cases and 3000 controls, half of whom will be Hispanic/Native American and half of whom will be non-Hispanic white women between the ages of 25 and 79. Molecular variants of genes that influence obesity and insulin (androgen receptor gene (AR), vitamin D receptor gene(VDR), insulin receptor (ADRB3)) will be examined both independently and in conjunction with metabolic factors to determine differences in genetic susceptibility in the population. Because of the diverse population (Hispanics, Native American, and non-Hispanic white women), the investigators propose to evaluate ethnic background and genetic admixture in relationship to gene markers, environmental factors, and breast and endometrial cancer risk. Genetic admixture (Ameridian to European genetic mixture) is a novel and innovative way to study the continuum of ethnic diversity. C-peptide, glycosylated hemoglobin, IGF-1, and IGFBP3 will be evaluated with respect to breast and endometrial cancer in a subset of women.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA078552-02
Application #
6173857
Study Section
Special Emphasis Panel (ZRG1-EDC-1 (01))
Program Officer
Patel, Appasaheb1 R
Project Start
1999-09-30
Project End
2004-07-31
Budget Start
2000-08-01
Budget End
2001-07-31
Support Year
2
Fiscal Year
2000
Total Cost
$444,660
Indirect Cost
Name
University of Colorado Denver
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045
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Connor, Avonne E; Visvanathan, Kala; Baumgartner, Kathy B et al. (2016) Ethnic differences in the relationships between diabetes, early age adiposity and mortality among breast cancer survivors: the Breast Cancer Health Disparities Study. Breast Cancer Res Treat 157:167-78
Slattery, Martha L; Lundgreen, Abbie; Hines, Lisa et al. (2015) Energy homeostasis genes and breast cancer risk: The influence of ancestry, body size, and menopausal status, the breast cancer health disparities study. Cancer Epidemiol 39:1113-22
John, Esther M; Sangaramoorthy, Meera; Hines, Lisa M et al. (2015) Body size throughout adult life influences postmenopausal breast cancer risk among hispanic women: the breast cancer health disparities study. Cancer Epidemiol Biomarkers Prev 24:128-37
Slattery, Martha L; Lundgreen, Abbie; John, Esther M et al. (2015) MAPK genes interact with diet and lifestyle factors to alter risk of breast cancer: the Breast Cancer Health Disparities Study. Nutr Cancer 67:292-304

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