Methylation patterns in colorectal cancer

描述（由申请人提供）：在此，我建议使用结直肠癌分子流行病学（MECC）研究，这是一项在以色列北方开展的基于大规模人群的结直肠癌病例对照研究，旨在研究结直肠癌的甲基化状态。该建议的总体假设是，甲基化状态代表了一组不同的CRC，可以独立预测CRC的总生存率。具体而言，目标是： 1.通过比较来自MECC病例的可用肿瘤和正常样本（约1450对样本）的甲基化组，测量散发性CRC中高甲基化基因的患病率; 2.确定高甲基化模式是否代表CRC的不同亚组; 3.评估高甲基化作为CRC的独立预后因素： a.使用以色列国家登记处和生命统计数据比较受试者的生存率; B.在存在其他经典报道的预后因素的情况下测量生存率。 这项研究解决了甲基化状态是否定义了一般人群中具有不同遗传，表观遗传和临床病理特征的肿瘤子集的问题。

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.