All ETDs from UAB

Advisory Committee Chair

Tim R Nagy

Advisory Committee Members

Stephen Barnes

James M Shikany

Helen Krontiras

Edmond K Kabagambe

Document Type

Dissertation

Date of Award

2012

Degree Name by School

Doctor of Philosophy (PhD) School of Health Professions

Abstract

The incidence of breast cancer is lower in Asia as compared to Western countries. However, the breast cancer risk among Asian immigrants living in Western countries reaches nearly as high as the Western country, suggesting environmental factors (e.g. diet and lifestyle) may be important for this geographical disparity. One dietary change of Asian immigrants is a reduction in soy consumption. Soy is rich in isoflavones, which compete with estrogen for receptor (ER) binding, and may protect against breast cancer. S-(-)equol, a metabolite of the soy isoflavone daidzein (DZ) has a higher bioavailability and greater affinity for ER than DZ. The first aim of this dissertation work was to systematically review the literature on the effects of soy isoflavones on breast cancer risk, with particular reference to the daidzein metabolite S-(-)equol. A second aim was to determine the prevalence of S-(-)equol producing status among postmenopausal women undergoing a physician recommended breast biopsy, and its association with biopsy outcome. Our third aim was to systemically review the published pre-clinical and clinical studies for role of phytoestrogens on cancer therapy. Results indicate that age at exposure, length and level of soy exposure are important factors for their effect on cancer prevention, and are different among Asians versus Westerners. The daily isoflavone intake levels among Asians have been reported around 100 mg/day compared to ~1 mg/day among Westerners. Asians who are exposed to soy early in life corresponding to nearly 60% reduction in breast cancer risk. Our data indicated a lower prevalence of S-(-)equol producers than previous reports of ~30% in general Western population. In this low soy consuming population (median 220 µg/day) no associations were observed between S-(-)equol producing status and ductal hyperplasia (OR 0.84; 95% CI 0.20 - 3.41), breast cancer (OR 0.57; 95% CI 0.61 - 2.0), or breast pathology (OR 0.68; 95% CI 0.23 - 1.99). Lack of side effects from phase I and II clinical trials of phytoestrogens in cancer therapy points toward their safety, and emerging evidence of role of soy in reduced recurrence and mortality are quite remarkable and opens opportunities for future research in this area.

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