Genetic and Epigenetic Markers for Colorectal Adenoma Recurrence

大多数结直肠癌起源于腺瘤性息肉，大部分腺瘤患者在初次息肉切除术后发展为新的（异时性）腺瘤。关于腺瘤患者在切除初始腺瘤后的适当监测间隔时间存在相当大的争议。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。该研究将在大约1,500名诊断为多发性腺瘤或病理学晚期腺瘤的患者中进行。这些患者已经在我们以前的研究中招募。除了临床和流行病学数据，我们已经从大部分研究参与者中获得了生殖系DNA样本，新鲜冷冻的息肉组织和福尔马林固定，石蜡包埋（FFPE）。在这项研究中，我们建议： 1)对研究参与者进行随访，以收集与随访检查和腺瘤复发相关的信息，并从尚未收集样本的其余患者中获得初始腺瘤的FFPE组织块 2)评估遗传和表观遗传肿瘤标志物与复发性腺瘤的相关性 3)评估腺瘤复发与GWAS鉴定的遗传变异的相关性 4)建立风险评估模型，评估遗传易感性和肿瘤标志物单独以及与已知预测因子（如初始腺瘤的病理特征）联合预测腺瘤复发风险的效用。 这项拟议的研究将提供重要的信息，这是有价值的，以确定高风险腺瘤患者进行密集的后续计划和化学预防。

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.