Genetic and Epigenetic Markers for Colorectal Adenoma Recurrence

大多数结直肠癌是由腺瘤性息肉引起的，很大一部分腺瘤患者在最初的息肉切除术后发展为新的（异时性）腺瘤。关于腺瘤患者切除初始腺瘤后的适当监测间隔存在相当大的争议。我们建议进行一项随访研究，以评估遗传易感性风险变异和肿瘤标志物与异时性腺瘤风险的关系。拟议的研究将在大约1500名诊断为多发性腺瘤或病理进展性腺瘤的患者中进行。这些患者已经在我们之前的研究中被招募。除了临床和流行病学数据，我们已经从大部分研究参与者那里获得了种系DNA样本、新鲜冷冻息肉组织和福尔马林固定石蜡包埋（FFPE）。在本研究中，我们提出：

Most colorectal cancers arise from adenomatous polyps, and a large proportion of adenoma patients develop new (metachronous) adenomas after their initial polypectomy. There is considerable controversy regarding an appropriate surveillance interval for adenoma patients after removal of their initial adenomas. We propose to conduct a follow-up study to evaluate both genetic susceptibility risk variants and tumor markers in relation to the risk of metachronous adenomas. The proposed study will be conducted in approximately 1,500 patients diagnosed with either multiple adenomas or a pathologically advanced adenoma. These patients have already been recruited in our previous studies. In addition to clinical and epidemiologic data, we have already obtained germline DNA samples, fresh-frozen polyp tissues, and formalin-fixed, paraffin-embedded (FFPE) from a large proportion of study participants. In this study, we propose to: 1) follow up with study participants to collect information related to follow-up exams and adenoma recurrence and to obtain FFPE blocks of initial adenomas from the remaining patients whose samples have not yet been collected 2) evaluate the association of genetic and epigenetic tumor markers with recurrent adenomas 3) evaluate the association of adenoma recurrence with GWAS-identified genetic variants 4) establish a risk-assessment model and evaluate the utility of genetic susceptibility and tumor markers alone and in combination with known predictors (such as pathologic features of initial adenomas) in predicting the risk of adenoma recurrence. This proposed study will provide critical information that is valuable to identify high-risk adenoma patients for intensive follow-up programs and chemoprevention.