Molecular Epidemiology of Colorectal Cancer

描述(申请人提供)：每年大约有140,000名美国人罹患结直肠癌，大约50,000人死于这种疾病。因此，预防结直肠癌将拯救许多美国人。结直肠肿瘤的起源是多因素的，外源性/环境因素可能导致(或阻止)特定的遗传和表观遗传学改变。更好地了解可改变的危险因素对结直肠癌发生的影响有助于优化预防策略。此外，外源性因素和肿瘤遗传学之间似乎有重要的相互作用，影响结直肠癌根治性切除后患者的生存。了解这些潜在的相互作用可能有助于提高患者的存活率。我们将利用两个大型前瞻性队列，护士健康研究(NHS)和卫生专业人员后续研究(HPFS)，这两个研究提供了30年期间的饮食和生活方式数据，长期生存数据，以及结直肠癌和腺瘤的石蜡包埋组织。这项建议的具体目的是：(1)研究一碳营养和酒精对结直肠癌遗传和表观遗传学改变的影响，以及这些营养因素和肿瘤遗传学/表观遗传学对患者生存的影响；(2)研究能量平衡对结直肠癌分子改变和患者生存的影响；(3)研究阿司匹林对结直肠癌发生和患者生存的影响。这些项目的完成将提高我们对外源性可修饰因子对结直肠肿瘤分子变化的影响的理解，以及这些外源性因素与肿瘤中可能影响根治性切除后患者生存的分子变化的潜在相互作用。具体目标的实现有助于优化预防策略，提高患者存活率。最后，这些项目将使我在数据库分析和流行病学研究方面获得宝贵的经验。我将在提议授予的头三年内完成哈佛公共卫生学院流行病学理学硕士学位的课程。这些项目将在查尔斯·福克斯博士的指导下进行，福克斯博士是临床肿瘤学和流行病学方面的知名研究员。在这些项目完成后，我将获得成为癌症流行病学独立研究员的经验。

DESCRIPTION (provided by applicant): Approximately 140,000 Americans develop colorectal cancer and approximately 50,000 individuals die from the disease every year. Thus, prevention of colorectal cancer will save many Americans. Colorectal neoplasia is multifactorial in origin, and exogenous / environmental factors may cause (or prevent) specific genetic and epigenetic alterations in colorectal neoplasia. A better understanding of effects of modifiable risk factors on colorectal carcinogenesis can help optimize preventive strategies. Moreover, there appear to be important interactions between exogenous factors and tumor genetics that influence the survival of patients following a curative resection of colorectal cancer. Understanding of these potential interactions may help improve patient survival. We will utilize two large prospective cohorts, the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS), which provide diet and lifestyle data over a 30-year period, long-term survival data, and paraffin-embedded tissue of colorectal cancers and adenomas. The specific aims of this proposal are: (1) to examine effects of one-carbon nutrients and alcohol on genetic and epigenetic alterations in colorectal neoplasia, and effects of these nutritional factors and tumor genetics / epigenetics on patient survival; (2) to examine effects of energy balance on molecular alterations of colorectal neoplasia and survival of patients; and (3) to examine effects of aspirin on colorectal carcinogenesis and survival of patients. Completion of these projects will improve our understanding of effects of exogenous modifiable factors on molecular alterations of colorectal neoplasia, and potential interactions of these exogenous factors and molecular alterations in tumor that may influence survival of patients after a curative resection. Accomplishment of the specific aims can help optimize preventive strategies and improve patient survival. Finally, these projects will allow me to gain invaluable experience in database analysis and epidemiologic research. I will complete courses for a Master of Science degree in Epidemiology at the Harvard School of Public Health during the first three years of the proposed award. The projects will be performed under the mentorship of Dr. Charles Fuchs, a well-established researcher in clinical oncology and epidemiology. At the completion of the projects, I will have gained the experience to become an independent researcher in cancer epidemiology.