Metabolic and Epidemiologic Evaluation of Choline and Betaine Intake

描述(由申请人提供)： 胆碱和甜菜碱是参与甲基代谢的营养物质，对DNA合成和甲基化至关重要。胆碱也是膜磷脂、磷脂酰胆碱和鞘磷脂的前体。动物研究表明，胆碱缺乏是在没有其他致癌物的情况下发生肝细胞癌的充分条件。没有胆碱和低蛋氨酸的缺乏甲基的饮食会促进化学诱导的动物癌症发生。与甲基代谢有关的饮食因素，包括叶酸、酒精和蛋氨酸，已经与人类几个器官的癌症有关。然而，胆碱和甜菜碱摄入量与人类癌症的关系尚不清楚。一些动物研究表明，胆碱缺乏后胆碱的补充实际上会促进癌症的发生。因此，胆碱与癌症之间的联系可能更为复杂，可能涉及甲基代谢以外的其他机制。由于缺乏食物成分数据，对胆碱和甜菜碱在人类健康中的作用的了解一直受到阻碍。最近，我们获得了我们的食物频率问卷测量的食物的胆碱和甜菜碱组成数据，发现在女性和男性中，较高的胆碱和甜菜碱摄入量与较低的空腹血浆同型半胱氨酸水平相关，在女性中，较高的胆碱摄入量与结直肠腺瘤的风险增加相关。在这项拟议的工作中，我们希望进一步扩大我们对饮食中胆碱和甜菜碱在甲基代谢和结肠癌发生中的生物学作用的认识。首先，使用弗雷明翰后代研究的数据，我们建议检查胆碱和甜菜碱摄入量与血浆甲硫氨酸后同型半胱氨酸水平的关系，同型半胱氨酸是甲基组代谢的中间产物，也是身体甲基组可利用性的潜在指标。评估蛋氨酸负荷后的同型半胱氨酸水平，而不是禁食水平，将提供有用的数据，模拟饭后的生物条件。我们预计将包括总共2732名具有饮食和血液数据的参与者。其次，我们将在健康专业人员后续研究中检查胆碱和甜菜碱摄入量与结直肠腺瘤和结直肠癌风险的关系，这是一项针对男性的大型前瞻性研究。我们预计有4143例腺瘤和1305例癌症。我们将利用现有的高质量和大容量数据集。由于我们从之前的资助中获得了胆碱研究方面的经验和知识，我们将能够以极具时间和成本效益的方式开展拟议的工作。拟议拨款的结果将补充我们之前在胆碱和甜菜碱方面的工作，并加强我们对这些营养物质在人类癌症发生中的作用的理解，因为这一领域的研究在很大程度上是未知的。

DESCRIPTION (provided by applicant): Choline and betaine are nutrients involved in methyl-group metabolism, which is critical for DNA synthesis and methylation. Choline is also a precursor of membrane phospholipids, phosphatidylcholine and sphingomyelin. Animal studies have demonstrated that choline deficiency is a condition sufficient for the development of hepatocellular carcinoma in the absence of other carcinogens. A methyl-group-deficient diet with no choline and low methionine promotes chemically induced carcinogenesis in animals. Dietary factors related to methyl- group metabolism, including folate, alcohol, and methionine have been associated with cancers of several organs in human. However, the relation between choline and betaine intake and human cancers is unknown. Some animal studies have shown that repletion of choline following choline deficiency actually promote carcinogenesis. Thus, the association between choline and cancer may be more complicated and may involve other mechanisms other than methyl-group metabolism. Understanding the role of choline and betaine in human health has been hampered by lack of food composition data. Recently, we obtained choline and betaine composition data for foods measured by our food frequency questionnaire and found that higher choline and betaine intake was associated with lower fasting plasma homocysteine levels in women and men and higher choline intake was associated with an elevated risk of colorectal adenoma in women. In this proposed work, we would like to further expand our knowledge on the biological role of dietary choline and betaine in methyl-group metabolism and colonic carcinogenesis. First, using data from the Framingham Offspring Study, we propose to examine the relation between choline and betaine intake and plasma levels of postmethionine-loading homocysteine, an intermediate product in methyl-group metabolism and a potential indicator of body's methyl-group availability. Evaluation of postmethionine-loading levels rather than fasting levels of homocysteine will provide useful data, simulating biological conditions after a meal. We expect to include a total of 2,732 participants with diet and blood data. Second, we will examine choline and betaine intake in relation to the risks of colorectal adenoma and colorectal cancer in the Health Professionals Follow-up Study, a large prospective study of men. We expect to have 4,143 adenoma and 1,305 cancer cases. We will take advantage of existing high-quality and large size datasets. Because we attained experience and knowledge in choline research from our previous grant, we will be able to carry out the proposed work in an extremely time- and cost-effective manner. The findings from the proposed grant will complement our previous work on choline and betaine and enhance our understanding of the role of these nutrients in carcinogenesis in human as this area of research is largely unexplored.