DNA REPAIR MEASURES AS BIOMARKERS FOR CANCER PREVENTION

这一重新提交提出了一个科学问题：开发一个连贯的 一个框架，合理地适应当前的生化和 流行病学研究结果对中国癌症预防工作的影响 普通民众。校长之间的强相互作用 研究人员、研究所和她的赞助商使这成为一种理想 KO-7奖研究和培训部分项目。这个 这项提议的主要焦点是抗氧化剂和酶的作用。 具有DNA修复能力，以便洞察他们的 它们之间的关系以及可能的致癌机制。 自由基被认为与癌症的发生有关。活性氧物种 以及其他以氧为中心的自由基可能起到肿瘤的作用 发起人或发起人，或两者都有。在初步病例对照中 比较，腺苷二磷酸核糖转移酶(ADPRT)和 DNA修复的相关酶学测量显示出很强的相关性 肺癌、结肠癌、结直肠息肉和乳腺癌 癌症。 建议进行两项流行病学研究：(1)病例对照研究和(2) 更大规模的前瞻性队列研究的可行性研究。初级阶段 提出的两项流行病学研究的目的是检验这一假说 癌症与DNA修复能力，ADPRT， UDS、O6-MGT和癌症状态，同时控制抗氧化剂 微量营养素、β-胡萝卜素、α-生育酚和抗坏血酸。一个 第二个主要目的是测试抗氧化剂与 以两种方式测量ADPRT、UDS和O6-MGT：(I)通过饮食 问卷调查和(Ii)血浆测定法。最后，这项建议包含 前瞻性队列研究的可行性研究，该研究将检查 这些协会前瞻性地为了测试他们的能力 预测癌症并提供测试干预措施的人群 来预防癌症。可行性研究的目标是：(A) 确定招聘程序，(B)制定干预办法，以及 (C)建立系统，以前瞻性地衡量本地区的癌症发病率 人口。 培训计划阐述了支持候选人使 从现场流行病学、生化和分子流行病学过渡 通过量身定做的课程、研讨会、咨询和手册 时髦。 在整个提案中，我们已经解决了审查员的关切。 具体地说，我们在引言中列出了他们的批评 科学部分(第16页)。讨论了因果关系的问题。 以及澄清时间承诺和 取肺组织样本。

This resubmission sets forth a scientific problem: to develop a coherent framework into which to rationally fit both current biochemical and epidemiologic findings so as to impact on cancer prevention efforts in the general population. The strong interactions among the Principal Investigator, the Institution, and her sponsors make this an ideal project for the research and training components of the KO-7 Award. The major focus of this proposal is on the role of anti-oxidants and enzymes with DNA repair capacity, in order to gain insight into their relationships and, possibly, the mechanism of carcinogenesis. Free radicals have been imputed in carcinogenesis. Active oxygen species as well as other oxygen-centered free radicals may act as tumor initiators or promoters, or both. In preliminary case-control comparisons, adenosine diphosphate ribosyl transferase (ADPRT) and related enzymatic measures of DNA repair have shown strong associations with lung cancer as well as colon cancer, colorectal polyps, and breast cancer. Two epidemiologic studies are proposed: (1) a case-control study and (2) a feasibility study for a larger, prospective cohort study. The primary aim of the two epidemiologic studies proposed is to test the hypothesis that cancer is associated with measures of DNA repair capacity, ADPRT, UDS, O6-MGT, and cancer status, while controlling for anti-oxidant micronutrients, Beta-carotene, alpha-tocopherol, and ascorbic acid. A second major aim is to test the associations of the antioxidants to the measures of ADPRT, UDS, and O6-MGT in two ways: (i) by dietary questionnaire and (ii) by plasma assay. Finally, this proposal contains a feasibility study for a prospective cohort study which will examine these associations prospectively in order to test their ability to predict cancer and to provide a population in which to test interventions to prevent cancer. The objectives of the feasibility study are to (a) define recruitment procedures, (b) develop intervention approaches, and (c) establish systems to measure cancer incidence prospectively in this population. The training program set forth support the candidate in making the transition from field epidemiology biochemical and molecular epidemiology through an tailored program of coursework, seminars, consultation and mento hip. Throughout the proposal, we have addressed the concerns of the reviewers. Specifically, we have itemized their criticisms in the Introduction to the Scientific Section (page 16). The issue of causality is addressed as well as clarification of the time commitments and the rationale for sampling lung tissue.