结直肠癌是最常见的消化系统恶性肿瘤之一,绝大多数的结直肠癌起源于腺瘤，且具有较长的癌前病变过程。编码lncRNA的DNA序列上某些位点的甲基化水平（简称lncRNA甲基化）可能通过影响lncRNA的表达水平和生物学功能，从而与结直肠腺瘤及结直肠癌的发生发展相关联。本项目在业已建立的结直肠腺瘤研究队列和结直肠癌预后随访队列的基础上，拟采用最新的生物信息学方法，在基因组水平分析lncRNA甲基化位点的分布特征，筛选出与结直肠腺瘤及结直肠癌发生发展潜在相关的lncRNA CpG位点；通过“病例-病例-对照”研究设计方法探讨lncRNA甲基化与结直肠腺瘤及结直肠癌发病之间的关系；并在组织学水平探讨相关lncRNA甲基化水平与lncRNA表达水平之间的关系，以期阐明lncRNA甲基化与结直肠腺瘤及结直肠癌发生发展之间的关联，为建立包含分子事件和环境暴露的多因素结直肠癌发病风险评估模型奠定科学基础。

Colorectal cancer (CRC) is a leading cause of cancer deaths worldwide. The conventional model of CRC formation describes a stepwise normal-adenoma-cancer progression and considers colorectal adenoma (CA) as the principal preneoplastic lesions leading to CRC. DNA methylation of lncRNAs may play an important role in the development of CA/CRC by affecting the expression and biological function of lncRNAs. Therefore, in the current application, we propose to explore the associations between methylation of lncRNAs and CA/CRC development on the basis of Colorectal Adenoma Cohort and Colorectal Cancer Prognosis Follow-up Cohort through three main steps: bioinformatic search, the case-case-control study, and the histological analysis. In the bioinformatic search part, we plan to construct a genome-wide lncRNA CpG database containing all the CpG site that are located within lncRNAs using the most updated lncRNA databases, and select CpG site that are potentially related with CA/CRC on the basis of lncRNA expression profiling databases and lncRNA function prediction databases. Then we will perform a case-case-control study to explore the associations between these lncRNA methylation and CA/CRC risk. Furthermore, we will perform the histological analysis of selected lncRNAs by genotyping assay and qRT-PCR analysis.