Colon Cancer Pathways: Hyperplastic Polyps and Adenomas

结肠癌途径：增生性息肉和腺瘤

• 批准号: 6723317
• 负责人: POLLY A NEWCOMB
• 金额: $ 52.73万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-17 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6723317
• 关键词: CpG islands; DNA methylation; adenomatous polyps; cancer risk; carbopolycyclic compound; chemical stability; clinical research; colon polyp; environment related neoplasm /cancer; epoxide hydrolase; genetic polymorphism; genetic screening; genetic susceptibility; human genetic material tag; human subject; hyperplasia; interview; neoplasm /cancer genetics; nucleic acid repetitive sequence; preneoplastic state

DESCRIPTION (provided by applicant): According to current clinical practice guidelines, hyperplastic polyps are benign lesions that can be safely ignored. However, recent evidence suggests that hyperplastic polyps, a common finding in nearly 30% of adults, may indeed be pre-neoplastic lesions. While only a minority of hyperplastic polyps progress to malignancy, the characteristics of those at-risk lesions are not fully known. In molecular terms, the presence of microsatellite instability (MSI) and/or CpG island methylation (CIMP) may be the hallmark of hyperplastic polyps that give rise to sporadic colorectal carcinomas. In this emerging paradigm, there is a great need to confirm these findings on a well-characterized sample, and more importantly, to understand the environmental and genetic characteristics that are associated with hyperplastic polyps, particularly in comparison to the better understood adenomas. To investigate the relationship between risk factors, epigenetic characteristics, and polyps, we propose to conduct a population based case-control study of hyperplastic polyps, adenomatous polyps, and normal controls. Individuals with a new diagnosis of polyps (hyperplastic polyps n=700, adenomas n=700) will be identified by a centralized review of the pathology files of Group Health Cooperative (GHC) of Puget Sound a large health maintenance organization. Similarly aged individuals with normal screening colonoscopies (n=700) will be identified from procedure files. All subjects will complete a standardized interview and provide a buccal sample. The diagnostic materials of all cases will be reviewed, DNA extracted from lesional blocks, and MSI and CIMP status will be assessed using standard panels of markers. Polymorphisms in epoxide hydrolase (mEH), which are involved in the detoxification of polyaromatic hydrocarbons in smoke and cooked meat, will be evaluated for their modifying effect on environmental exposures. This study will provide the largest study of risk factors for hyperplastic polyps, their genetic characterization, and comparisons to adenomas and normals. In this study neoplastic pathways will be classified on the basis of genetic instability, DNA methylation phenotype, and epidemiologic risk factors. The results of this study will have implications for understanding the biology and prevention of colorectal cancer.

描述（由申请人提供）：根据当前的临床实践指南，增生性息肉是良性病变，可以安全地忽略。然而，最近的证据表明，增生性息肉（常见于近 30% 的成年人）可能确实是肿瘤前病变。虽然只有少数增生性息肉进展为恶性肿瘤，但这些高危病变的特征尚不完全清楚。从分子角度来看，微卫星不稳定性 (MSI) 和/或 CpG 岛甲基化 (CIMP) 的存在可能是导致散发性结直肠癌的增生性息肉的标志。在这个新兴的范式中，非常需要在充分表征的样本上证实这些发现，更重要的是，了解与增生性息肉相关的环境和遗传特征，特别是与更好理解的腺瘤相比。为了研究危险因素、表观遗传特征和息肉之间的关系，我们建议对增生性息肉、腺瘤性息肉和正常对照进行基于人群的病例对照研究。新诊断息肉（增生性息肉 n = 700，腺瘤 n = 700）的个体将通过对大型健康维护组织普吉特湾团体健康合作社（GHC）的病理档案进行集中审查来确定。具有正常筛查结肠镜检查的相似年龄个体（n=700）将从程序文件中被识别。所有受试者将完成标准化访谈并提供口腔样本。将审查所有病例的诊断材料，从病变块中提取 DNA，并使用标准标记组评估 MSI 和 CIMP 状态。环氧化物水解酶（mEH）的多态性参与烟和熟肉中多环芳烃的解毒，将评估其对环境暴露的改变作用。这项研究将对增生性息肉的危险因素、其遗传特征以及与腺瘤和正常人的比较进行最大规模的研究。在这项研究中，肿瘤途径将根据遗传不稳定性、DNA 甲基化表型和流行病学危险因素进行分类。这项研究的结果将对了解结直肠癌的生物学和预防产生影响。