SCREENING MARKERS FOR COLORECTAL CANCER

目前的结直肠癌筛查方式并不是普遍存在的 可接受的，而且由于成本和低特异性的原因，不太可能 应用广泛。以满足进一步筛查的迫切需要 策略，我们建议评估一种基于生物学的筛选方法 这将结合多种细胞和分子途径来 肿瘤。这个项目和整个P01的重点是氧化 损伤和细胞凋亡。此外，有几条路径是 结直肠癌变将被评估为早期的可能目标 侦测工作。将进行人体和动物研究。至 确定区分腺瘤、增生性腺瘤患者的标志物 来自健康对照组的息肉、溃疡性结肠炎和腺癌 建议收集各种生物材料(血液、结肠 活检、原发病变、直肠刷检、大便)和危险因素 普吉特湾患者群体卫生合作情况(n=800) 接受临床指示的结肠镜检查。来自中国的个人标本 将对每个诊断类别进行评估：特定标记 氧化损伤；凋亡蛋白的异常(bcl2，bclx， BAX)；谷胱甘肽和谷胱甘肽转移酶的表达；雌激素的高甲基化 受体基因；细胞增殖异常(Ki-67)；以及 细胞-细胞间的相互作用(连接蛋白和E-钙粘蛋白)。分析将探索 这组生物中的每一组的敏感性和特异性 代表致癌物质的几条途径的相关标记，以及 目标是建立一个标记集合，以促进 肿瘤及癌前病变携带者的识别 损伤。最终，我们计划评估筛查的效果，使用 这些标记在一项前瞻性筛查试验中，我们将为 P01更新。

Current colorectal cancer screening modalities are not universally acceptable, and, for reasons of cost and low specificity, unlikely to be widely applied. To address the exigent need for further screening strategies, we propose to evaluate a biologically based screening approach that will incorporate a variety of cellular and molecular pathways to neoplasia. The focus of this project-and the entire P01- is on oxidative damage and apoptosis. Additionally, several pathways that are unique to colorectal carcinogenesis will be evaluated as possible targets for early detection efforts. Both human and animal studies will be conducted. To identify markers that discriminate patients with adenomas, hyperplastic polyps, ulcerative colitis, and adenocarcinomas from healthy controls, we propose to collect a variety of biologic materials (blood, colonic biopsies, primary lesions, rectal brushings, stool) and risk factor information on Group Health Cooperative of Puget Sound patients (n=800) undergoing clinically indicated colonoscopy. Specimens from individuals in each of the diagnostic categories will be evaluated for: specific markers of oxidative damage; aberrations in apoptosis proteins (bcl-2, bcl-x, bax); glutathione and GST expression; hypermethylation of the estrogen receptor gene; abnormalities in cell proliferation (Ki-67); and aspects of cell-cell interaction (connexins and E-cadherin). Analyses will explore the sensitivity and specificity of each of this group of biologically relevant markers that represent several pathways to carcinogens, with the goal of establishing an ensemble of markers that can facilitate the identification of individuals carrying neoplastic and pre-neoplastic lesions. Ultimately, we plan to evaluate the efficacy of screening using these markers in a prospective screening trial, which we will plan for the P01 renewal.