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Phase I Induction and Estrogen Metabolism in Women With and Without Breast Cancer and in Response to a Dietary Intervention

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Annual rept. 30 Sep 2001-29 Sep 2002

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Work by our group and others provide the scientific basis of this study 1-11. Cross-national studies of breast cancer rates and studies of migrants indicate that environmental factors are responsible for large population-level differences in breast cancer rates and rates of change over time. In a study of 46 countries, we found that over 90 of breast cancer mortality could be accounted for mainly by dietary factors 12. On a per-calorie basis, the strongest effect in the data was the protective effect of cabbage. There is some evidence that vegetables in the Brassica genus, like cabbage and broccoli, modify estrogen metabolism by causing 17beta- Estradiol E2 to be metabolized to 2-hydroxyestrone 2HE rather than 16alpha-hydroxyestrone 16HE. Relative to 2HE, 16HE appears more likely to cause cancer and breast cancer patients have a lower ratio of these metabolites than do disease-free controls. It has further been shown that the P450 enzyme CYP 1Beta1 is present in tumor but not normal breast tissue. The indole glucosinolates IGSL, which are contained in high concentrations in Brassica vegetables, induce a number of protein products that can shift E2 metabolism away from 16HE and towards 2HE. AhR activation also induces immune system factors such as interleukin- 1beta IL-1beta and other proteins, such as plasminogen activator inhibitor-2 PAI-2, a protease inhibitor that has been associated with inhibition of tumor invasiveness metastasis.

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  • Medicine and Medical Research
  • Food, Food Service and Nutrition

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