A Mediterranean Diet in for Colon Cancer Prevention

描述(申请人提供)：地中海饮食预防结肠癌：流行病学和动物研究表明，传统克里坦-地中海饮食的主要成分在预防结直肠癌方面有很大希望，同时改善整体健康。与美国饮食相比，地中海饮食中n-6脂肪酸、多不饱和脂肪和红肉的含量较低，而植物性食物和单不饱和脂肪的摄入量较高。这一建议背后的假设是，坚持地中海式饮食将导致人类结肠粘膜中n-6脂肪酸的减少，n-3和n-9脂肪酸的增加。这一点，再加上饮食中其他方面，如水果和蔬菜中植物化学物质的摄入量增加，预计将调节正常大肠粘膜中的二十烷类代谢，使其处于抗癌状态，从而降低结肠增殖。我们将招募120名患有结直肠癌风险增加的研究参与者。受试者将随机接受改良的地中海饮食或2010年健康人群饮食，为期6个月。地中海饮食将被设计为减少多不饱和脂肪的摄入量，增加单不饱和脂肪、水果和蔬菜的摄入量。预计这些饮食变化不仅会减少促炎介质和增加抗炎介质，还会改变环氧合酶和脂氧合酶产生的二十烷类化合物的类型。我们对这种新的交换清单饮食的试点测试表明，受试者可以做出非常大的饮食变化。对干预前后的饮食摄取数据、血液样本和乙状结肠镜检查的正常粘膜组织进行分析，并比较两组患者饮食前和干预后的变化。特定的终点是血液和粘膜中的脂肪酸和类胡萝卜素，粘膜中炎症介质的类型和水平，以及粘膜中的增殖。我们预计，与地中海饮食相比，2010年健康人饮食将产生最小的变化。增加我们对饮食变化对人类粘膜影响的了解，是评估饮食在预防结直肠癌方面的潜力的基础。这些数据还将验证使用这些生物标记物筛选其他以饮食和/或药物为基础的干预措施，目的是减缓或逆转癌症发生。如果结肠直肠癌风险的粘膜生物标记物(前列腺素E2、其他二十烷类化合物、增殖)显示出有益的效果，这些数据可能被用来证明对疾病终点和更详细的饮食研究进行更大规模的前瞻性干预是合理的。

DESCRIPTION (provided by applicant): A Mediterranean Diet for Colon Cancer Prevention: Epidemiological and animal studies indicate that the major components of the traditional Cretan-Mediterranean diet have great promise for the prevention of colorectal cancer while improving overall health. Relative to the American diet, the Mediterranean diet is lower in n-6 fatty acids, polyunsaturated fats, and red meat while intakes of plant-based foods and monounsaturated fats are higher. The hypothesis behind this proposal is that adherence to a Mediterranean type of diet will result in a decrease in n-6 fatty acids and increased n-3 and n-9 fatty acids in human colonic mucosa. This, together with other aspects of the diet such as increased intakes of phytochemicals in fruits and vegetables, is expected to modulate eicosanoid metabolism in normal colorectal mucosa to its anticarcinogenic state resulting in lower colonic proliferation. We will recruit 120 study participants who are at increased risk of colorectal cancer. Subjects will be randomized to a modified Mediterranean diet or a Healthy People 2010 diet for 6 months. The Mediterranean diet will be designed to decrease polyunsaturated fat intake and to increase intakes of monounsaturated fats, fruits and vegetables. These dietary changes are expected to not only decrease pro-inflammatory mediators and increase anti-inflammatory mediators, but to also change the types of eicosanoids that are produced from cyclooxygenases and lipoxygenases. Our pilot testing of this novel exchange list diet indicates that subjects can make very large dietary changes. Dietary intake data, blood samples and biopsies of normal mucosa from flexible sigmoidoscopy will be analyzed before and after intervention, and changes from baseline will be compared in the 2 diet arms. The specific endpoints are fatty acids and carotenoids in blood and mucosa, the types and levels of inflammatory mediators in the mucosa, and proliferation in the mucosa. We expect that the Healthy People 2010 diet will result in minimal changes relative to the Mediterranean diet. Increasing our understanding of the effects of dietary changes on human mucosa is fundamental to evaluating the potential of diet in colorectal cancer prevention. Such data would also validate the use of these biomarkers as screen for other dietary and/or pharmaceutical-based interventions aimed at slowing or reversing carcinogenesis. If beneficial effects can be demonstrated in mucosal biomarkers of colorectal cancer risk (prostaglandin E2, other eicosanoids, proliferation), such data may be used to justify a larger, prospective intervention with disease endpoints and more detailed dietary studies.