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

• 批准号: 8655145
• 负责人: POLLY A NEWCOMB
• 金额: $ 64.74万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 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/8655145
• 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

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侧重于检测和去除晚期腺瘤息肉。但是，最近的证据表明，另外一组息肉，无链锯齿状的息肉（SSP）是结直肠癌的重要前体，也可能需要提高警惕性。先前将SSP与增生息肉（HPS）分组，通常认为病变没有恶性潜力。现在，越来越多的共识表明，SSP属于结直肠癌的“锯齿状途径”。该途径产生的肿瘤通常位于近端结肠中，其特征是具有CpG岛甲基表型（CIMP），并且经常在BRAF中表现出突变。这项研究的长期目标是表征新的高风险群体，以提高结直肠癌筛查的有效性。在朝着这一目标努力的过程中，我们提出了一项研究，以研究SSP的临床意义，以解决以下特定目的：1）确定与HPS相对于HPS和无息肉对照的SSP相关的随后结直肠瘤的风险； 2）评估随后与SSP相关的随后肿瘤的风险根据息肉特征而变化，例如大小，近端位置和SSP的数量； 3）确定SSP和HP的分子特征（例如BRAF-MON和CIMP状态）之间的关联，以及随后的结直肠瘤形成的风险。为了实现这些目标，我们提出了一项回顾性队列研究，其中7800名综合医疗保健提供系统（GH）的成员。男女24-74岁，从1998 - 2007年开始接受基线结肠镜检查，并接受了HPS的临床诊断（n = 3,900），并且比较基线时没有结直肠病理的结肠镜检查患者（n = 3,900）将有资格进行这项研究。在基线时具有临床诊断HPS的队列成员将在我们先前对结直息息肉的研究中进行标准病理审查，并在我们先前的研究中进行验证，以确认诊断并根据标准的组织学标准区分SSP。医疗记录将被提取以收集基线息肉的数据 特征和队列成员人口统计。与西部华盛顿西部的监视，流行病学和最终结果癌症注册表和GH病历至2013年1月1日将用于回顾性确定事件的结肠直肠息肉和弗兰克的结直肠癌。对于AIM 3，我们将在基线时使用HPS或SSP的患者中使用嵌套的病例对照方法，收集基线息肉组织，并使用Taqman PCR和CIMP使用结直肠癌特异性Methight PCR PCR面板（CACNA1G，IGF2，IGF2，NEUROG1，NEUROG1，RUNX3，RUNX3和SOCS1）来测试BRAF突变。这将是评估与SSP相关的结果的最大人群研究，并首先评估Braftation和CIMP-STATUS作为晚期肿瘤风险的潜在生物标志物。我们的研究结果将具有极大的公共健康重要性，将提供数据以为临床试验开发提供信息，并最终影响临床医生对不同结直肠癌筛查方案的脊髓息肉的分类者的方式。