DNA REPAIR MEASURES AS BIOMARKERS FOR CANCER PREVENTION

这一重新提交提出了一个科学问题：发展一个连贯的 合理地适应当前的生物化学和 流行病学研究结果，以影响癌症预防工作， 普通民众。 校长之间的强烈互动 研究者、机构和她的赞助商使这成为一个理想的选择。 KO-7奖的研究和培训部分的项目。 的 该建议的主要重点是抗氧化剂和酶的作用 具有DNA修复能力，以便深入了解它们的 关系和可能的致癌机制。 自由基被认为是致癌的原因。 活性氧物种 以及其他以氧为中心的自由基可能作为肿瘤 引发剂或促进剂或两者。 初步病例对照 比较，腺苷二磷酸核糖基转移酶（ADPRT）和 DNA修复的相关酶促测量显示出强烈的关联性， 肺癌、结肠癌、结肠直肠息肉和乳腺癌 癌 两个流行病学研究建议：（1）病例对照研究和（2） 一项更大规模的前瞻性队列研究的可行性研究。 主 这两项流行病学研究的目的是检验这一假设 癌症与DNA修复能力，ADPRT， UDS、O 6-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 第二个主要目的是测试抗氧化剂与 ADPRT，UDS和O 6-MGT的措施在两种方式：（i）饮食 问卷调查和（ii）血浆分析。 最后，该提案包含 一项前瞻性队列研究的可行性研究， 这些协会前瞻性地，以测试他们的能力， 预测癌症并提供一个测试干预措施的人群 来预防癌症 可行性研究的目标是：（a） （B）制定干预措施， (c)建立系统来测量癌症发病率， 人口 所列的培训计划支持候选人在 从现场流行病学、生物化学和分子流行病学 通过量身定制的课程，研讨会，咨询和曼托计划 臀部. 在整个提案中，我们处理了审查人员的关切。 具体而言，我们已在《 第16页（科学）。 因果关系的问题得到解决 以及澄清时间承诺和理由， 取样肺组织

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.