Methylation patterns in colorectal cancer

描述(申请人提供)：在这里，我建议使用结直肠癌分子流行病学(MECC)研究，这是一项基于以色列北部结直肠癌的大型人群病例对照研究，以调查结直肠癌的甲基化状态。这一建议的总体假设是，甲基化状态代表了一组不同的CRC，可以独立地预测CRC的总体存活率。具体地说，目标是： 1.通过比较现有肿瘤和来自MECC病例的正常样本(约1450个配对样本)上的甲基化小组，测量散发性结直肠癌中高甲基化基因的发生率； 2.确定超甲基化模式是否代表CRC的不同亚群； 3.评估高甲基化是结直肠癌的独立预后因素： A.使用以色列国家登记册和生命统计数据比较受试者的存活率； B.在存在其他经典报道的预后因素的情况下测量存活率。 这项研究解决的问题是，甲基化状态是否定义了普通人群中具有不同遗传、表观遗传和临床病理特征的肿瘤的子集。

DESCRIPTION (provided by applicant): Here, I propose to use the Molecular Epidemiology of Colorectal Cancer (MECC) study, a large population-based case-control study of colorectal cancer in northern Israel, to investigate methylation status in colorectal cancer. The overall hypothesis of this proposal is that methylation status represents a distinct group of CRCs that may independently predict overall survival from CRC. Specifically, the goals are to: 1. Measure the prevalence of hypermethyled genes in sporadic CRC by comparing the methylation panel on available tumor and normal samples (approximately 1450 paired samples) from MECC cases; 2. Determine if patterns of hypermethylation represent distinct subgroups of CRC; 3. Evaluate hypermethylation as an independent prognostic factor in CRC: a. Using Israeli national registries and vital statistics compare survival in subjects; b. Measure survival in the presence of other classically reported prognostic factors. This research addresses the question of whether methylation status defines a subset of tumors with distinct genetic, epigenetic and clinicopathologic characteristics in the general population.