A Cohort Study of Sessile Serrated Polyps and Subsequent Colorectal Neoplasia

无蒂锯齿状息肉和随后的结直肠肿瘤的队列研究

基本信息

批准号：
8452499
负责人：
POLLY A NEWCOMB
金额：
$ 66.81万
依托单位：
FRED HUTCHINSON CANCER RESEARCH CENTER
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-04-22 至 2017-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8452499
关键词：
Address Adenocarcinoma Adenomatous Polyps Affect Appearance BRAF gene Biological Markers CACNA1G gene Caliber Cancer Patient Caring Case Series Characteristics Clinical Clinical Management Clinical Trials Cohort Studies Colon Colon Carcinoma Colonoscopy Colorectal Colorectal Cancer Colorectal Neoplasms Colorectal Polyp Consensus CpG Island Methylator Phenotype DNA Data Detection Development Diagnosis Dysplasia Effectiveness Excision Exhibits Goals Guidelines Health High Prevalence Hyperplastic Polyp IGF2 gene Incidence Individual Large Intestine Carcinoma Lesion Literature Location Longitudinal Studies Malignant - descriptor Malignant Neoplasms Medical Records Medical Surveillance Methylation Molecular Mutation Neoplasms Nomenclature Outcome Pathology Pathway interactions Patients Polyps Public Health Recommendation Regimen Relative (related person)Risk Serrated Adenoma System Testing Time Tissues Tooth structure Triage United States Villous Washington Woman Work abstracting adenoma aged base case control clinical Diagnosis clinically significant cohort colonic crypt colorectal cancer screening comparison group demographics evidence based guidelines follow-up health care delivery high risk improved member men mortality neoplasm registry patient population prevent public health relevance screening tumor vigilance

项目摘要

DESCRIPTION (provided by applicant): Colorectal cancer screening guidelines currently focus on the detection and removal of advanced adenomatous polyps. However, recent evidence implicates an additional group of polyps, sessile serrated polyps (SSPs), as important precursors to colorectal cancer that may also warrant increased vigilance. SSPs were previously grouped with hyperplastic polyps (HPs), lesions routinely believed to have no malignant potential. Now, there is growing consensus that SSPs belong on the "serrated pathway" to colorectal cancer. Tumors resulting from this pathway are usually located in the proximal colon, characterized as having a CpG island methylator phenotype (CIMP), and often exhibit mutations in BRAF. The long term goal of this study is to characterize new high-risk groups to improve the effectiveness of colorectal cancer screening. In working towards this goal, we propose a study to examine the clinical significance of SSPs that addresses the following specific aims: 1) determine the risk of subsequent colorectal neoplasia associated with SSPs relative to HPs and polyp-free controls; 2) evaluate whether the risk of subsequent neoplasia associated with SSPs varies according to polyp characteristics, such as size, proximal location, and the number of SSPs; 3) determine the association between molecular characteristics of SSPs and HPs, such as BRAF-mutation and CIMP-status, and risk of subsequent colorectal neoplasia. To accomplish these aims, we propose a retrospective cohort study among 7,800 members of the integrated healthcare delivery system, Group Health (GH). Men and women, aged 24-74, who received a baseline colonoscopy from 1998-2007 and had a clinical diagnosis of HPs (N=3,900) and a comparison group of colonoscopy patients with no colorectal pathology at baseline (N=3,900) will be eligible for this study. Cohort members with clinically diagnosed HPs at baseline will undergo a standard pathology review, developed and validated in our prior studies of colorectal polyps, to confirm the diagnosis and to distinguish SSPs according to standard histological criteria. Medical records will be abstracted to gather data on baseline polyp characteristics and cohort member demographics. Linkage to the Western Washington Surveillance, Epidemiology, and End Results cancer registry and GH medical records through January 1, 2013 will be used to retrospectively ascertain incident colorectal polyps and frank colorectal carcinoma. For Aim 3, we will use a nested case-control approach among those with HPs or SSPs at baseline, collect baseline polyp tissue, and test tissue DNA for BRAF mutation using TaqMan PCR and CIMP using a colorectal cancer-specific MethyLight PCR panel (CACNA1G, IGF2, NEUROG1, RUNX3, and SOCS1). This will be the largest cohort study to evaluate outcomes associated with SSPs and the first to evaluate BRAF- mutation and CIMP-status as potential biomarkers for advanced neoplasia risk. Our study findings will have great public health importance, will provide data to inform clinical trial development, and ultimately affect the way clinicians triage individuals with serrated polyps to different colorectal cancer screening regimens.

描述（由申请人提供）：结直肠癌筛查指南目前重点关注晚期腺瘤性息肉的检测和切除。然而，最近的证据表明另一类息肉，即无蒂锯齿状息肉（SSP），是结直肠癌的重要前兆，也可能需要提高警惕。 SSP 以前被与增生性息肉 (HP) 归为一类，通常认为这些病变没有恶性潜力。现在，越来越多的人认为 SSP 属于结直肠癌的“锯齿状途径”。由该途径产生的肿瘤通常位于近端结肠，其特征为具有 CpG 岛甲基化表型 (CIMP)，并且经常表现出 BRAF 突变。这项研究的长期目标是确定新的高危人群的特征，以提高结直肠癌筛查的有效性。为了实现这一目标，我们提出了一项研究来检验 SSP 的临床意义，该研究旨在实现以下具体目标：1）确定与 HP 和无息肉对照相比，与 SSP 相关的后续结直肠肿瘤风险； 2) 评估与SSP相关的后续肿瘤形成的风险是否根据息肉特征（例如大小、近端位置和SSP的数量）而变化； 3) 确定 SSP 和 HP 的分子特征（例如 BRAF 突变和 CIMP 状态）与随后结直肠肿瘤风险之间的关联。为了实现这些目标，我们建议对综合医疗服务系统 Group Health (GH) 的 7,800 名成员进行一项回顾性队列研究。 1998-2007 年接受基线结肠镜检查并临床诊断为 HP 的男性和女性（N=3,900），年龄 24-74 岁，对照组为基线时无结直肠病理的结肠镜检查患者（N=3,900）。有资格参加这项研究。基线时临床诊断出 HP 的队列成员将接受标准病理学审查，该审查是在我们之前的结直肠息肉研究中开发和验证的，以确认诊断并根据标准组织学标准区分 SSP。将提取医疗记录以收集基线息肉数据特征和队列成员人口统计数据。截至 2013 年 1 月 1 日，与西华盛顿州监测、流行病学和最终结果癌症登记和 GH 医疗记录的联系将用于回顾性确定结直肠息肉和直肠癌的发生情况。对于目标 3，我们将在基线具有 HP 或 SSP 的患者中使用巢式病例对照方法，收集基线息肉组织，并使用 TaqMan PCR 和 CIMP 使用结直肠癌特异性 MethyLight PCR panel (CACNA1G) 测试组织 DNA 的 BRAF 突变、IGF2、NEUROG1、RUNX3 和 SOCS1）。这将是评估与 SSP 相关的结果的最大队列研究，也是第一个评估 BRAF 突变和 CIMP 状态作为晚期肿瘤风险潜在生物标志物的队列研究。我们的研究结果将对公共卫生具有重大意义，将为临床试验的开发提供数据，并最终影响临床医生将锯齿状息肉患者分类到不同结直肠癌筛查方案的方式。