Abstract IA25: Nutritional intervention for prevention of ovarian cancer in a natural model: The laying hen.

Ovarian cancer is a lethal disease with poor prognosis due to the late stage at which it is usually detected. Research has been hampered by lack of suitable animal models. With the exception of the laying hen, no other accessible animal model recapitulates the human disease hens get ovarian cancer spontaneously, present with same gross and histological pathology, and provide feasible model for conducting large scale dietary interventions. Moreover, each of the histological subtypes of ovarian cancer seen in the human disease are observed in the hen with varying frequency. We have shown that the up-regulation of E-cadherin (CDH1) is an early defining step in ovarian cancer hens, analogous to the human disease. Rigidity of the tissue, discerned by touch, and positive E-cadherin staining, assist in the diagnosis of early ovarian cancer from hens with no apparent pathology. Flaxseed is the richest vegetable source of the potent anti-inflammatory omega-3 polyunsaturated fats (OM3) in the germ and the phytoestrogen lignan secoisolariciresinol diglucoside (SDG) in the hull. Cancer-prone old laying hens were fed a diet enriched with flaxseed for one year and we observed a significant reduction in ovarian cancer severity, but not a reduction in ovarian cancer incidence. However, a significant decrease in the incidence of ovarian cancer, as well as severity, was seen when hens were provided flaxseed throughout their whole egg laying life. These long term feeding studies which are initiated when hens are at different ages have helped us to define the window of therapeutic intervention which enables significant amelioration and prevention of ovarian cancer. We hypothesize that the two biologically active constituents of flaxseed work in concert to reduce the incidence and severity of ovarian cancer resulting in suppression and prevention of this deadly disease. Feeding hens specific diets enriched with the individual components of flaxseed (OM3, SDG) vs. OMG6 (corn oil) provides insight into their separable actions. OM3 enriched diets reduce systemic oxidative stress while OM6 caused an increase in systemic oxidative stress. The reduction in cancer severity and incidence was correlated to a reduction in cyclooxygenase (COX) enzymes and prostaglandin E2 (PGE2). The phytoestrogen lignan SDG reduced pro-proliferative estrogen signaling and estrogen mediated genotoxicity, contributing to the preventative effects. Alteration in the pattern of estrogen metabolites provides a read-out of the therapeutic effectiveness and may provide the basis for development of a biomarker for early disease. Research on dietary intervention not only provides development of therapeutic modalities, but provides new insights into basic biology of ovarian cancer. These studies provide the foundation for a new flax meal-based clinical trial on progression-free remission in ovarian cancer. {NIH/NCCAM AT005295 and NIH/NCI CA162511} Citation Format: Dale Buck Hales. Nutritional intervention for prevention of ovarian cancer in a natural model: The laying hen. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr IA25.