Prospective Studies of Colorectal Adenoma

描述（由申请人提供）：本提案旨在通过将哈佛大学公共卫生学院的指导研究经验与正式课程相结合，丰富Andrew T. Chan博士在癌症预防流行病学方面的职业发展。拟议的研究旨在利用三个大型前瞻性随访队列——护士健康研究（NHS）、卫生专业人员随访研究（HPFS）和塞来昔布预防腺瘤（APC）试验的资源来改善结直肠癌的预防。分析将集中在三个有希望的预防领域，这些领域补充了现有的筛查和切除腺瘤的努力，腺瘤是绝大多数结直肠癌的前驱病变。

DESCRIPTION (provided by applicant): This proposal is designed to enrich Andrew T. Chan, MD's career development in cancer prevention epidemiology through an integration of mentored research experience with formal coursework at the Harvard School of Public Health. The proposed research aims to improve prevention of colorectal cancer using the resources of three large, prospectively followed cohorts -- the Nurses' Health Study (NHS), the Health Professionals Follow-up Study (HPFS), and the Adenoma Prevention with Celecoxib (APC) Trial. The analyses will focus on three promising areas of prevention which complement existing efforts in screening and removal of adenomas, the precursor lesions for the vast majority of colorectal cancer. First, the research plan seeks to clarify the role of aspirin, non-steroidal anti-inflammatory drugs, and cyclooxygenase-2 selective inhibitors in chemoprevention. In particular, the analyses will provide urgently needed data on the optimal dose and duration of use of such agents for the prevention of initial adenoma in an average risk population. Moreover, the role of genetic variation in metabolism of these drugs in modulating their potential benefit will be investigated. Second, the proposal will examine modifiable risk factors, which are common to coronary heart disease (CHD) and colorectal adenoma and investigate the application of current CHD biomarkers in the prediction of colorectal neoplasia. Finally, the planned research aims to clarify the role of hyperplastic polyps in risk stratification for subsequent adenoma. To pursue these aims, Dr. Chan will design prospective studies using multivariable models. The overarching methodological strength is the inclusion of three large cohorts with complementary features: the NHS and HPFS allow analysis of initial colorectal adenoma, with extended follow-up and repeated exposure measures; the APC trial permits analysis of recurrent adenoma, with uniform surveillance of subjects. This research plan will provide important information on adenoma prevention and risk assessment for improved population-based surveillance and screening. Moreover, Dr. Chan will obtain experience in several study designs -- including observational cohort, case-control, and clinical trials -- and data ranging from questionnaires, biomarkers, and genetic polymorphisms. This overall proposal will ensure that Dr. Chan will become an established independent investigator and a leader in cancer prevention.