Therapeutic Efficacy of Flax Seed in the Prevention of Ovarian Cancer

描述（由申请人提供）：在美国，每年有超过24,000名女性被诊断患有卵巢癌，其中一半的女性死于这种疾病。尽管在筛查和治疗方面取得了进展，但缺乏对潜在病因的了解限制了预防策略。典型的西方饮食，多吃肉，少吃蔬菜，可能与卵巢癌的发病率呈正相关。omega -3 （OM-3FA）和omega -6 （OM-6FA）脂肪酸的不平衡会增加患癌症的风险。研究表明，与摄入较少OM-3FA的人群相比，摄入大量OM-3FA的人群患乳腺癌、前列腺癌和结肠癌的几率更低。因此，增加OM-3FA的摄入量可能是一种无毒的方法来预防卵巢癌，增加癌症治疗和显着延长寿命。亚麻籽是膳食纤维、OM-3FA α -亚麻酸（ALA）以及木脂素的极好来源，木脂素是有效的抗雌激素，在某些癌症中具有抗增殖和促凋亡活性。本研究将以蛋鸡卵巢癌模型为研究对象，检验亚麻籽饲粮的有效性，并探讨OM-3FA和肠道雌激素的作用机制。除了衰老的母鸡，没有其他动物模型的自发性上皮性卵巢癌模仿人类疾病。我们假设富含亚麻籽的饲粮可以降低蛋鸡卵巢癌的发病率。确定受亚麻膳食影响的分子靶点，将有助于深入了解卵巢癌的病因，并为开发以功能性食品为基础的饮食干预，预防和治疗女性卵巢癌提供基础。提出三个具体目标：1)确定在蛋鸡饲粮中添加亚麻籽降低卵巢癌发病率的有效剂量范围；2)确定亚麻籽日粮对卵巢癌炎症及前列腺素相关机制的影响；3)确定亚麻籽日粮对卵巢癌雌激素相关机制的影响。公众对使用OM-3FA减少癌症的兴趣相当大，母鸡模型为研究饮食干预在预防卵巢癌中的功效提供了重要机会。相关性：卵巢癌是一种高度致命的疾病，由于缺乏合适的动物模型，对卵巢癌的研究受到了限制，因为除了蛋鸡之外，没有其他动物患与妇女相同类型的卵巢癌。以母鸡为模型，我们将研究使用omega-3/亚麻籽饮食作为预防卵巢癌的一种方法。

DESCRIPTION (provided by applicant): More than 24,000 women in the United States are diagnosed with ovarian cancer every year, and half of these women die from their disease. Despite advances in screening and treatment, the lack of understanding of the underlying etiology has limited prevention strategies. A typical Western diet, which is high in meats and low in vegetables, may be positively associated with ovarian cancer incidence. An imbalance of omega 3 (OM-3FA) and omega 6 (OM-6FA) fatty acids contributes to excess cancer risk. Studies indicate that populations that consume high amounts of OM-3FA have lower incidences of breast, prostate and colon cancers than do those that consume less OM-3FA. Thus increasing the consumption of OM-3FA may be a nontoxic way to prevent ovarian cancer, augment cancer therapy and to significantly increase life span. Flax seed is an excellent source of dietary fiber, the OM-3FA alpha-linolenic acid (ALA), as well as lignans, which are potent anti- estrogens that have been shown to have anti-proliferative and pro-apoptotic activities in certain cancers. The proposed studies will test the effectiveness of a flax seed enriched diet, and examine the mechanism of action of OM-3FA and enteroestrogens using the laying hen as a model of ovarian carcinoma. With the exception of the aging hen, there are no other animal models of spontaneous epithelial ovarian cancer that mimic the human disease. We hypothesize that a flax seed enriched diet will reduce the incidence of ovarian carcinoma in the laying hen. Identification of molecular targets whose expression is affected by flax enriched diet will provide insight into the etiology of ovarian cancer and will provide the foundation for developing functional food based dietary intervention for the prevention and treatment of ovarian cancer in women. Three Specific Aims are proposed: 1) Determine the effective dose range of flax seed added to the hen diet that reduces the incidence of ovarian cancer; 2) Determine the effect of flax seed diet on inflammation and prostaglandin- associated mechanisms involved in ovarian cancer; 3) Determine the effect of flax seed diet on estrogen- associated mechanism involved in ovarian cancer. There is considerable public interest in the use of OM-3FA to reduce cancer and the hen model provides an important opportunity to investigate the efficacy of dietary intervention in the prevention of ovarian cancer. Relevance: Research into ovarian cancer, a highly lethal disease, has been limited by the lack of suitable animal models, because, with the exception of the laying hen, no other animals are inflicted with the same type of ovarian cancer that affects women. Using the hen as our model we will investigate the use of omega-3/flax seed diet as a way to prevent ovarian cancer.