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Risk of Breast Cancer Among Smokers
Attributable to a MT/ER Biomarker
Lisa M. Gallicchio, MS
School of Medicine, University of Maryland, Baltimore
Epidemiological studies have shown inconsistent results with regard to an association between smoking and breast cancer. It has been suggested, however, that studying a heterogeneous group of women may mask molecular differences that cause some women to be more susceptible to the effects of cigarettes' chemical carcinogens than others. Among these carcinogens is the heavy metal cadmium, which has been shown to exert estrogen-like effects in breast tissue by binding to the estrogen receptors (ERs). The bioavailability of cadmium of the ERs, however, likely depends on the metal-binding protein metallothionein (MT). This proposal tests the hypothesis that MT plays a major role in regulating the bioavailability of cadmium to the ER and hence controls the putative estrogenic action of this metal in the development of breast cancer among women who are exposed to elevated levels of cadmium via smoking. It is specifically hypothesized that the MT/ER ratio will be significantly higher in women smokers who have not developed breast cancer. To further clarify the role of cadmium in the development of breast cancer, comparisons of MT/ER ratios will be made for women smokers and nonsmokers who have developed cancer as well as for women smokers and nonsmokers who have not developed cancer. Cancerous and normal breast tissue, as well as smoking status information, will be obtained from the Cooperative Human Tissue Network (CHTN). Laboratory techniques (Western blot/ELISA) will be used to measure MT and ER levels in the tissue. Characterization of MT/ER ratios may help to determine individual susceptibility to breast cancer for those exposed to cadmium, either through smoking or through other sources, and help to resolve existing epidemiological inconsistencies with regard to smoking and breast cancer.
