SCREENING MARKERS FOR COLORECTAL CANCER

目前的结直肠癌筛查模式并不普遍 可接受的，并且由于成本和低特异性的原因，不太可能 广泛应用。为了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， 它将整合多种细胞和分子途径， 肿瘤形成这个项目和整个P01的重点是氧化 损伤和凋亡。此外，一些独特的途径， 结直肠癌发生将被评估为早期治疗的可能靶点。 侦查工作。将进行人类和动物研究。到 识别区分患有腺瘤、增生性 我们从健康对照组的息肉、溃疡性结肠炎和腺癌中， 建议收集各种生物材料（血液、结肠 活检、原发病变、直肠刷检、粪便）和风险因素 普吉特湾患者团体健康合作社的信息（n=800） 进行临床结肠镜检查。从个人的标本， 将对每种诊断类别进行评估：特定标志物 氧化损伤;凋亡蛋白（bcl-2，bcl-x， bax）;谷胱甘肽和GST表达;雌激素高甲基化 受体基因;细胞增殖异常（Ki-67）;以及 细胞间相互作用（连接蛋白和E-钙粘蛋白）。分析将探索 这组生物学指标中每一个的灵敏度和特异性 代表致癌物几种途径的相关标志物， 目标是建立一套标志， 识别携带肿瘤和肿瘤前的个体 病变最后，我们计划使用以下方法评估筛查的有效性： 这些标志物在一个前瞻性的筛选试验，我们将计划为 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.