STUDIES OF PERSONS AT HIGH RISK OF CANCER

对癌症高危人群的研究

• 批准号: 3963384
• 负责人: M A TUCKER
• 金额: --
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3963384
• 关键词: DNA repair; adult human (21+); autoimmune disorder; bone marrow exam; cancer information system; cancer registry /resource; cancer risk; chemical related neoplasm /cancer; child (0-11); computer assisted diagnosis; cytogenetics; drug adverse effect; early diagnosis; environment related neoplasm /cancer; hairy cell leukemia; histocompatibility antigens; human T cell leukemia; human subject; hybridomas; immunogenetics; leukemia; leukocyte antigen typing; longitudinal human study; neoplasm /cancer diagnosis; neoplasm /cancer education; neoplasm /cancer epidemiology; neoplasm /cancer genetics; neoplasm /cancer immunology; nevus; occupational hazard; oncogenic virus; online computer; patient /disease registry; pediatric neoplasm /cancer; preneoplastic state; questionnaires; radiation related neoplasm /cancer; sarcoma; serology /serodiagnosis; skin neoplasms; tissue /cell culture; viral leukemogenesis

The purpose of this project is to (a) conduct and coordinate interdisciplinary studies on members of cancer-prone families and other high-risk populations to clarify the role of genetic mechanisms and host-environmental interactions in human carcinogenesis; and (b) assess, quantify, and elucidate the determinants of the cancer risks associated with therapeutic exposure to cytotoxic drugs. Project staff also conduct or collaborate with other EEB investigators in epidemiologic case-control studies of specific cancers or cohort studies of specific exposures that are particularly relevant to this project. A series of project resources has been developed in support of our research, including: (1) a computerized registry of cancer-prone families; (2) a biospecimen repository which processes, stores and distributes biological samples from persons at high risk of cancer; (3) a fibroblast repository/tissue culture facility; and (4) a series of contract-supported laboratories which provide immunologic, cytogenetic, and DNA repair assay capabilities. Persons at high risk of cancer are evaluated clinically and donate biological samples. Clinical, epidemiologic, genetic, and laboratory studies are combined to elucidate mechanisms of cancer susceptibility. The familial melanoma project is a prototype of this approach, in which clinical (dysplastic nevi), genetic (autosomal dominant transmission of a gene possibly linked to the RJ locus) and biologic (enhanced sensitivity to the cytotoxic and mutagenic effects of UV radiation) risk factors have been identified. The therapeutic administration of cytotoxic drugs, many of which are carcinogenic in laboratory animals, provides an opportunity to explore the cancer patients treated with specific cytotoxic drugs are conducted. The leukemogenicity of specific alkylating agents has been documented, differences in leukemogenic potential among various agents identified, and evidence for an increasing risk of leukemia with increasing drug dose obtained.

该项目的目的是 (a) 进行和协调 对易患癌症的家庭成员和其他人进行跨学科研究 高危人群阐明遗传机制的作用和 人类致癌过程中宿主与环境的相互作用； (b) 评估， 量化并阐明相关癌症风险的决定因素 治疗性暴露于细胞毒性药物。 项目人员还进行 或与其他 EEB 研究人员合作进行流行病学病例对照 对特定癌症的研究或对特定暴露的队列研究 与该项目特别相关。 系列项目资源 已开发用于支持我们的研究，包括：（1） 易患癌症家庭的计算机化登记； (2) 生物样本 处理、储存和分发生物样本的储存库 癌症高危人群； (3) 成纤维细胞储存库/组织培养 设施; (4)一系列合同支持的实验室，提供 免疫学、细胞遗传学和 DNA 修复检测能力。 人员位于 对癌症高风险进行临床评估并捐赠生物 样品。 临床、流行病学、遗传学和实验室研究 结合起来阐明癌症易感性机制。 家族的 黑色素瘤项目是这种方法的原型，其中临床 （发育不良痣），遗传（基因的常染色体显性遗传） 可能与 RJ 位点有关）和生物制剂（增强对 紫外线辐射的细胞毒性和致突变作用）危险因素已被 确定。 细胞毒性药物的治疗性给药，许多 对实验动物具有致癌性，提供了机会 探索接受特定细胞毒性药物治疗的癌症患者 实施。 特定烷化剂的致白血病性已被证实 据记录，不同药物之间的致白血病潜力存在差异 已确定，并且有证据表明，随着年龄的增长，患白血病的风险也会增加 获得的药物剂量。