Dr. Martha L. Slattery, Ph.D.

Professor, Division of Clinical Epidemiology

Title: FOUR-CORNERS BREAST AND ENDOMETRIAL CANCER STUDY - NIH National Cancer Institute

The incidence of breast cancer 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 cancer identified in non-Hispanic white women (i.e. 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 we focus on the metabolic factors of obesity/weight changes and indicators of insulin status as they relate to breast cancer. 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 it binding proteins (IGFBPs) and well as indirectly through its effect on estrogen levels. We focus 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 2½ hour in-person interview and a blood draw. Over a three-year case ascertainment period, we will enroll 3000 breast 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 and have been shown to have functional significance [androgen receptor gene (AR), vitamin D receptor gene (VDR), insulin receptor substrate factor-1 gene (IRS-1), IGF-1, sex hormone binding globulin (SHBG), and beta-3-adrenergic 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), we will evaluate ethnic background and genetic admixture in relationship to gene markers, environmental factors, and breast cancer risk. Genetic admixture (Amerindian to European genetic mixture) is a novel and innovative way to study the continuum of ethnic diversity that will be used as an independent risk factors, a stratification variable and a confounding variable. C-peptide, glycosylated hemoglobin, IGF-1, and IGFBP3 will be evaluated in a subset of women.

Principal Investigator:

• Martha L. Slattery, Ph.D.
Marty.Slattery@hsc.utah.edu

Co-Investigators:

      • Carol Sweeney, Ph.D.
         Carol.Sweeney@hsc.utah.edu
      • Roger Wolff, Ph.D.
         Roger.Wolff@hsc.utah.edu

Biostatistician:

• Jennifer Herrick
Jennifer.Herrick@hsc.utah.edu

Administration:

      • Tricia Sweeney
         Tricia.Sweeney@hsc.utah.edu
      • Nefi Aquilar
         Nefi.Aguilar@hsc.utah.edu