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Cancer Control Research

Abstract

DESCRIPTION (provided by applicant): Breast cancer is the most common female malignancy in the United States and among patients with stage 1 and II disease, the 10-year risk of recurrence is estimated at 20-40%. Although prognostic/predictive tumors markers for breast cancer recurrence have been extensively studied, limitations in our understanding of the environmental and host genetic factors that predict for breast cancer survivorship contribute to many women receiving unnecessary aggressive therapy. Obesity is a risk factor for poorer breast cancer outcome and though the mechanism is unclear, it is believed that a large component of the risk is mediated by an "obesity- induced" insulin resistance state. Insulin resistance may also influence breast cancer prognosis independent of obesity. Indeed there is epidemiological evidence linking hyperinsulinemia/insulin resistance to an increased risk of recurrence and breast cancer mortality after adjustment for BMI. In the absence of biological measures of metabolic changes related to insulin resistance, we hypothesize that single-nucleotide polymorphisms (SNPs) of candidate genes that are associated with insulin resistance could be important genetic markers contributing to aggressive tumor characteristics at diagnosis and poorer breast cancer outcome. The application utilizes the resources of the unique data and tissue repository, the "Early Stage Breast Cancer Repository" (ESBCR), an NCI funded retrospective cohort study of 2,000 women with stage I and II breast cancer treated at M. D. Anderson Cancer Center (MDACC) between 1985 and 2000. The specific aims are 1: To investigate the correlation between SNPs of candidate genes involved in insulin resistance (insulin, insulin growth factor 1, insulin receptor substrate, insulin growth factor binding protein-3, leptin, tumor necrosis factor-alpha, adiponectin and interluekin-6) and breast cancer characteristics (tumor size, grade, lymph-node metastasis, estrogen/progesterone receptor and HER-2/neu status); 2: To investigate the association between the candidate genes and risk of breast cancer recurrence and breast cancer specific death adjusting for known clinical and tumor prognostic factors. The results of this study will help us to better predict women who have a high chance of having a recurrence of their breast cancer. This information will be useful in identifying women who may benefit from interventions to decrease insulin resistance as part of their breast cancer care.