Insulin Resistance and Colon Cancer in Blacks and Whites

描述（由申请人提供）：本项目的长期目标是确定结肠癌病因学中胰岛素抵抗、遗传和环境风险因素之间的相互作用，并为申请人提供分子流行病学和生物信息学方面的进一步职业发展培训。 Keku博士，申请人，是一个助理教授在斯坦福大学。 她的导师是罗伯特·密立根博士和凯·隆德博士。 密立根博士是一位知名的分子流行病学家。 他是卡罗莱纳乳腺癌研究的首席研究员，也是国际合作的一部分，研究阳光和遗传因素在恶性黑色素瘤病因学中的相互作用。 隆德博士是分子生物学和生理学教授，也是IGF系统与GI疾病相关的专家。 他们建议为Keku博士提供分子流行病学和生物信息学方面的指导性职业培训，利用公共卫生学院和医学院细胞和分子生理学系的资源。 作为指导职业发展培训的一部分，这项研究是一项关于非裔美国人和白人胰岛素抵抗（胰岛素/IGF）和结肠癌的病例对照研究。 结肠癌是美国最常见的胃肠道恶性肿瘤。 非裔美国人结肠癌发病率和死亡率的上升构成了严重的公共卫生问题。 本研究的具体目的是：1）在非裔美国人和白色受试者中检查胰岛素/IGF轴与结肠癌的关系。 2)评估胰岛素/IGF轴基因多态性的作用及其与结肠癌和相关危险因素的关系。 3)研究非裔美国人和白色结肠癌患者和非结肠癌患者胰岛素/IGF轴与胰岛素抵抗相关因素之间的关系。 拟定研究将利用来自基于人群的结肠癌病例对照研究（NCI R 01 CA 66635）的可用标本和测量值。 我们将使用血浆和DNA标本分别测定胰岛素、IGF-I、IGF-II、IGFBP-1、IGFBP-3、葡萄糖和C肽水平，并进行基因分型试验。 实验室检测结果将与生活方式/饮食信息合并，并分析相关性。 拟议的项目将促进非裔美国人和白人对胰岛素抵抗在结肠癌中的作用的理解。

DESCRIPTION (provided by applicant): The long-term goals of this project are to define the interactions between insulin resistance, genetic and environmental risk factors in the etiology of colon cancer and to achieve further career development training for the applicant in molecular epidemiology and bioinformatics. Dr. Keku, the applicant, is an Assistant Professor at UNC. Her mentors are Drs. Robert Millikan and Kay Lund. Dr. Millikan is an established molecular epidemiologist. He is the Principal Investigator of the Carolina Breast Cancer Study and also part of an international collaboration investigating the interactions between sunlight and genetic factors in the etiology of malignant melanoma. Dr. Lund is a Professor of Molecular Biology and Physiology and an expert on the IGF system as it relates to GI disease. They propose a mentored career training for Dr. Keku in molecular epidemiology and bioinformatics utilizing the resources at the UNC School of Public Health and the Department of Cell and Molecular Physiology in the School of Medicine. The study proposed as part of the mentored career development training is a case-control study of insulin resistance (insulin/IGF) and colon cancer in African Americans and whites. Colon cancer is the most common gastrointestinal malignancy in the United States. The rise in the incidence and mortality of colon cancer in African Americans poses a serious public health problem. The specific aims of this study are: 1)To examine the association between insulin/IGF axis and colon cancer in African American and white subjects with and without colon cancer. 2) To evaluate the role of genetic polymorphisms in the insulin/IGF axis and their relationship to colon cancer and associated risk factors. 3) To examine the association between the insulin/IGF-axis and factors related to insulin resistance in African American and white subjects with and without colon cancer. The proposed study will utilize available specimens and measurements from a population based case-control study of colon cancer (NCI R01 CA66635). We will use plasma and DNA specimens to determine insulin, IGF-I, IGF-II, IGFBP-1, IGFBP-3, glucose and C-peptide levels and for genotyping assays respectively. The results of the laboratory assays will be merged with lifestyle/dietary information and analyzed for associations. The proposed project will advance the understanding of the role of insulin resistance in colon cancer among African Americans and whites.