Insulin, the IGF Axis, and Colorectal Neoplasia

描述（由申请人提供）：癌症预防，控制和 人口科学职业发展奖将提供一个优秀的 我有机会获得和完善必要的技能， 高质量的人群胃肠道癌预防研究 水平 我提出的研究计划包括严格评估一个及时的 与结直肠癌预防直接相关的中心假设。 使用一系列不同的一般，分子和遗传流行病学 我打算探讨有关的未解决或未经审查的问题， 高胰岛素血症单独或与 胰岛素样生长因子（IGF）轴蛋白，与 结直肠癌发生 细胞培养实验的现有数据， 动物模型系统和人类观察研究支持这一假设， 然而，许多重要问题仍有待解决。 背景下 指导研究，我计划进行（1）类型2的历史队列研究 糖尿病（DM）和结直肠腺癌风险，（2）病例对照 2型糖尿病与结直肠腺瘤风险研究（3）巢式病例对照 血清胰岛素/胰岛素样生长因子轴蛋白水平与结直肠癌关系的研究 腺癌风险，（4）IGF轴mRNA表达水平的初步研究， 肿瘤性与非肿瘤性结直肠粘膜，和（5）一个前瞻性的 有或无胰岛素样生长因子轴基因多态性受试者的队列研究 结直肠肿瘤 这些研究应该提供有意义的科学 数据，同时让我广泛接触和相当多的 使用几种重要的研究工具。 进一步增强 我的职业发展，我计划获得相关领域的教学培训， 胃肠癌预防研究（包括负责任的行为 研究）。 此外，我打算担任一名癌症教师， 马约研究生院的流行病学课程。 我赞助的资源 机构是优秀的，将促进成功，高效 完成我的总体目标。 在实现这些目标后，我 我有信心，我将准备好继续我的职业生涯，作为一个成功的 致力于学术研究的独立调查员。

DESCRIPTION (provided by applicant): The Cancer Prevention, Control, and Population Sciences Career Development Award will provide an excellent opportunity for me to acquire and refine the skills necessary to conduct high-quality gastrointestinal cancer prevention research at a population level. My proposed research plan involves the rigorous evaluation of a timely central hypothesis with direct relevance to colorectal cancer prevention. Using a series of different general, molecular, and genetic epidemiologic approaches, I intend to explore unresolved or unexamined issues related to the possibility that hyperinsulinemia, either alone or in combination with insulin-like growth factor (IGF) axis proteins, is causally linked to colorectal carcinogenesis. Existing data from cell culture experiments, animal model systems, and human observational studies support this hypothesis, yet many essential questions remain to be addressed. In the context of mentored research, I plan to perform (1) a historical cohort study of type 2 diabetes mellitus (DM) and colorectal adenocarcinoma risk, (2) a case-control study of type 2 DM and colorectal adenoma risk, (3) a nested case-control study of serum insulin/IGF axis protein concentrations and colorectal adenocarcinoma risk, (4) a pilot study of IGF axis mRNA expression levels in neoplastic versus non-neoplastic colorectal mucosa, and (5) a prospective cohort study of IGF axis gene polymorphisms among subjects with or without colorectal neoplasia. These studies should provide meaningful scientific data, while simultaneously affording me a broad exposure to and considerable experience with several important investigational tools. To further enhance my career development, I plan to obtain didactic training in areas relevant to gastrointestinal cancer prevention research (including the responsible conduct of research). Additionally, I intend to serve as an instructor for a cancer epidemiology course at Mayo Graduate School. The resources of my sponsoring institution are excellent and will facilitate the successful, efficient completion of my overall objectives. Following achievement of these goals, I am confident that I will be ready to continue my career as a successful independent investigator committed to academic research.