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Glucose Metabolism and Breast Density: a Pathway for Breast Cancer Etiology


Breast cancer is the most common cancer in women, and a leading cause of cancer death in Europe. We propose to improve understanding of breast cancer etiology by investigating the metabolic effect of glucose and genetic variants implicated in glucose metabolism and breast mammographic density, one of the strongest known risk factors for breast cancer. There is increasing evidence that obesity and diabetes mellitus are associated with increased risk of breast carcinomas. Biological and epidemiological data provide support for a role of glucose and other factors related to glucose metabolism, such as insulin and insulin-like growth factors (IGFs), in breast cancer development. However, it is still not clear how impaired glucose metabolism exerts its influence on breast cancer risk.

Mammographic density (MD) refers to variations in the breast among women that reflect differences in tissue composition. Women who have >75% of their breast area as dense tissue have a risk of breast cancer 3-6 times great er than women of the same age with zero area representing one of the most powerful predictors of breast cancer. The proposed study aims to investigate whether glucose metabolism influences risk of breast cancer through direct effects on proliferative activity and quantity of stromal and epithelial tissue in the breast, that is reflected in mammograpic density. Thus, we postulate that genetic and metabolic factors related to glucose metabolism influence breast tissue composition through effects on the level s of exposure to growth factors such as IGF-1 that are mitogens in the breast resulting in greater quantities of stromal and epithelial tissue in the breast, increase susceptibility to carcinogens, and risk of breast cancer. The long term goal of the propos ed investigation is to understand the etiology of breast cancer, and to use this knowledge to guide the development of preventive strategies for the disease.

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