Therapeutic Efficacy of Flax Seed in the Prevention of Ovarian Cancer

描述（由申请人提供）：美国每年有超过24，000名妇女被诊断患有卵巢癌，其中一半妇女死于这种疾病。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，肉类含量高，蔬菜含量低，可能与卵巢癌发病率呈正相关。欧米茄3（OM-3FA）和欧米茄6（OM-6 FA）脂肪酸的不平衡导致癌症风险过高。研究表明，摄入大量OM-3FA的人群患乳腺癌、前列腺癌和结肠癌的发病率低于摄入较少OM-3FA的人群。因此，增加OM-3FA的消耗可能是预防卵巢癌、增强癌症治疗和显著延长寿命的无毒方式。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，已显示在某些癌症中具有抗增殖和促凋亡活性。拟议的研究将测试亚麻籽丰富的饮食的有效性，并检查OM-3FA和肠雌激素的作用机制，使用蛋鸡作为卵巢癌的模型。除了衰老的母鸡，没有其他自发性上皮性卵巢癌的动物模型可以模仿人类疾病。我们推测，亚麻籽丰富的饮食将减少卵巢癌的发病率在蛋鸡。鉴定其表达受富含亚麻的饮食影响的分子靶点将提供对卵巢癌病因学的深入了解，并将为开发基于功能性食物的饮食干预以预防和治疗女性卵巢癌提供基础。提出了三个具体目的：1）确定母鸡饮食中添加亚麻籽降低卵巢癌发病率的有效剂量范围; 2）确定亚麻籽饮食对卵巢癌中涉及的炎症和前列腺素相关机制的影响; 3）确定亚麻籽饮食对卵巢癌中涉及的雌激素相关机制的影响。公众对使用OM-3FA减少癌症有相当大的兴趣，母鸡模型为研究饮食干预预防卵巢癌的有效性提供了重要机会。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限制，因为除了产蛋母鸡之外，没有其他动物会患上影响妇女的同类卵巢癌。使用母鸡作为我们的模型，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.