COLON NEOPLASIA STUDIES--GENETIC/ENVIRONMENTAL RESOURCE

结肠肿瘤研究——遗传/环境资源

• 批准号: 3200987
• 负责人: JOHN D POTTER
• 金额: $ 23.25万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-06-01 至 1995-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3200987
• 关键词: acetylation; body physical activity; caloric dietary content; colon neoplasms; dietary calcium; dietary constituent; dietary fiber; dietary lipid; dietary proteins; environment related neoplasm /cancer; family genetics; gel electrophoresis; gene expression; gene interaction; genotype; human genetic material tag; human subject; nutrition related neoplasm /cancer; nutrition related tag; phenotype; questionnaires; reproduction; southern blotting

The investigators are currently undertaking two NCI-funded case-control studies of colon cancer (2400 cases and 24 control) and adenomatous polyps of the large bowel (600 cases and 1800 controls), investigating the role of diet, physical activity, reproduction, and family history. The two studies were designed to answer similar questions using similar instruments. It is increasingly clear that, in addition to the environmental factors, genetic susceptibility is important in the etiology of these disorders. Since the original submission of CA48998, much progress has been made in Utah and elsewhere in identifying genes associated with colon cancer. The FAP gene is located on 5q21 and the search for it has now been narrowed to a small region, less than 400 kilobases. It is expected that this gene (whether or not it is the recently identified MCC gene) will be cloned and sequenced before the completion of data collection, allowing genotyping of the case-control study subjects. Further, it is appropriate to consider at least one other marker for restriction fragment length polymorphism (RFLP) analysis, namely fast-acetylator genotype, for which there is evidence, albeit inconsistent, of an association with colon cancer. Three polymorphisms have now been identified. Southern Blot analysis allows direct determination of acetylator-genotype. Other candidate markers will be identified over the next few years. The specific aims of this proposal are: 1. To collect blood from participants in the 2 population-based studies of colon cancer (R01 CA48998) and adenomatous polyps (P01 CA50305; 2. To analyze DNA from all participants to explore the role of acetylator status and the FAP gene in the etiology of colon neoplasia; and 3. To explore the evidence for confounding and interaction between the genotypes and diet, particularly intake of meat, fat, protein, but also of total calories, calcium, micronutrients, and fiber, and physical activity, reproduction, and family history, in the etiology of colon neoplasia. 4. To store white blood cells and DNA for future analysis of specific genes as they become available from the work at Utah or elsewhere. The combined environment/diet/gene dataset will provide the first and perhaps the most comprehensive opportunity to determine the way in which genes and environment interact in the etiology of colon cancer and its precursor lesion.

调查人员目前正在进行两项由 NCI 资助的病例控制 结肠癌（2400 例病例和 24 例对照）和腺瘤研究 大肠息肉（600 例病例和 1800 例对照），正在调查 饮食、体力活动、生殖和家族史的作用。 这两项研究旨在使用类似的方法回答类似的问题 仪器。越来越明显的是，除了 环境因素、遗传易感性很重要 这些疾病的病因学。自最初提交 CA48998 以来， 犹他州和其他地方在识别基因方面取得了很大进展 与结肠癌有关。 FAP基因位于5q21， 搜索现已缩小到一个小区域，不到 400 个 千碱基。预计该基因（无论是否是 最近发现的 MCC 基因）将在 完成数据收集，可以对病例对照进行基因分型 研究科目。此外，适当考虑至少一项 其他限制性片段长度多态性 (RFLP) 标记 分析，即快速乙酰化基因型，有证据表明， 尽管不一致，但与结肠癌有关。三 现已鉴定出多态性。 Southern Blot 分析允许 直接测定乙酰基基因型。其他候选标记 将在未来几年内确定。 该提案的具体目标是： 1. 从两项基于人群的研究中收集参与者的血液 结肠癌（R01 CA48998）和腺瘤性息肉（P01 CA50305； 2. 分析所有参与者的DNA，探讨 乙酰化状态和结肠肿瘤病因中的 FAP 基因； 和 3. 探索不同因素之间混杂和相互作用的证据 基因型和饮食，特别是肉类、脂肪、蛋白质的摄入量，而且 总热量、钙、微量营养素和纤维以及体能 结肠病因中的活动、生殖和家族史 瘤形成。 4. 储存白细胞和DNA以供将来分析特定的 从犹他州或其他地方的工作中获得的基因。 组合的环境/饮食/基因数据集将提供第一个和 也许是确定如何实现这一目标的最全面的机会 基因和环境在结肠癌及其病因学中相互作用 前驱病变。