Integrative Modeling of Genetic and Epigenetic Variation in Colorectal Cancer

描述（由申请人提供）： 虽然可以通过早期发现和改变风险因素来预防，但结直肠癌（CRC）仍然是一个主要的公共卫生问题。早期表观遗传改变和低叶酸饮食的消费已被证明会导致CRC，可能是由于异常的DNA甲基化。然而，DNA甲基化的倾向及其与基因-饮食相互作用的关系尚未在前瞻性收集饮食信息的研究中进行评估。该提案的总体目标是在注释良好的前瞻性护士健康研究和健康专业人员随访研究中描述782例CRC病例中基因遗传变异和异常DNA甲基化之间的关联。特定的目的是很好地评价局部DNA序列背景可能影响局部甲基化倾向的假设。这些数据将增强我们对结直肠癌病因学中表观遗传事件相关性的理解。

DESCRIPTION (provided by applicant): Although preventable through early detection and modification of risk factors, colorectal cancer (CRC) remains a major public health concern. Early epigenetic alterations and consumption of a low-folate diet have been shown to lead to CRC, possibly due to aberrant DNA methylation. However, the propensity for DNA methylation and its association with gene-diet interactions have not been assessed in a study with prospectively collected dietary information. The overall goal of this proposal is to characterize the association between genetic variation and aberrant DNA methylation of genes in 782 CRC cases in the well-annotated prospective Nurses' Health Study and Health Professionals Follow-up Study. The specific aims are well-powered to evaluate the hypothesis that local DNA sequence context may affect local methylation propensity. These data will enhance our understanding of the association of epigenetic events in colorectal cancer etiology.