Phase I Induction and Estrogen Metabolism in Women with and without Breast Cancer and in Response to a Dietary Intervention
Abstract
Work by our group and others provide the scientific basis of this study. 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. 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 (l6HE). Relative to 2HE, l6HE 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 CYP1B1 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 l6HE and towards 2HE. AhR activation also induces immune system factors such as interleukin-Ibeta (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).
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2000
- Accession Number
- ADA389716
Entities
People
- James R Hébert
Organizations
- University of South Carolina