Molecular Epidemiology of Colorectal Cancer

描述（由申请人提供）：大约140,000美国人患结直肠癌，每年大约50,000人死于该疾病。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）结直肠肿瘤中特定的遗传和表观遗传改变。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存在重要的相互作用，影响结肠直肠癌根治性切除术后患者的生存。了解这些潜在的相互作用可能有助于提高患者的生存率。我们将使用两个大型前瞻性队列，护士健康研究（NHS）和卫生专业人员随访研究（HPFS），提供30年期间的饮食和生活方式数据，长期生存数据和结直肠癌和腺瘤石蜡包埋组织。本提案的具体目的是：(1)研究一碳营养素和酒精对结直肠肿瘤遗传和表观遗传改变的影响，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)探讨能量平衡对结直肠肿瘤分子改变及患者生存的影响；(3)探讨阿司匹林对结直肠癌发生及患者生存的影响。这些项目的完成将提高我们对外源性可改变因素对结直肠癌分子改变的影响的理解，以及这些外源性因素和肿瘤分子改变之间可能影响根治性切除后患者生存的潜在相互作用。具体目标的实现有助于优化预防策略，提高患者生存率。最后，这些项目将使我获得宝贵的数据库分析和流行病学研究经验。我将在拟议奖项的前三年完成哈佛大学公共卫生学院流行病学硕士学位的课程。这些项目将在Charles Fuchs博士的指导下进行，Charles Fuchs博士是临床肿瘤学和流行病学领域的知名研究员。在项目完成后，我将获得成为一名独立的癌症流行病学研究人员的经验。

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.