Insulin Resistance and Colon Cancer in Blacks and Whites

描述(由申请者提供)：该项目的长期目标是明确胰岛素抵抗、遗传和环境风险因素在结肠癌病因中的相互作用，并为申请者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。申请者Keku博士是北卡罗来纳大学的助理教授。她的导师是罗伯特·米利根博士和凯·隆德博士。米利根博士是一位著名的分子流行病学家。他是卡罗莱纳州乳腺癌研究的首席研究员，也是一个国际合作的成员，该合作研究了阳光和遗传因素在恶性黑色素瘤病因中的相互作用。伦德博士是分子生物学和生理学教授，也是与胃肠道疾病相关的胰岛素样生长因子系统的专家。他们建议利用北卡罗来纳大学公共卫生学院和医学院细胞和分子生理学系的资源，为Keku博士提供分子流行病学和生物信息学方面的指导职业培训。 作为有指导的职业发展培训的一部分，这项研究是对非裔美国人和白人的胰岛素抵抗(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一个严重的公共卫生问题。本研究的具体目的是：1)在患有和不患有结肠癌的非裔美国人和白人受试者中，研究胰岛素/胰岛素样生长因子轴与结肠癌的关系。2)探讨胰岛素/胰岛素样生长因子轴基因多态性与结肠癌及其相关危险因素的关系。3)探讨非裔美国人和白人结肠癌患者胰岛素/胰岛素样生长因子-轴与胰岛素抵抗相关因素之间的关系。这项拟议的研究将利用基于人群的结肠癌病例对照研究(NCI R01CA66635)中可用的样本和测量数据。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、血糖和C-肽水平，并进行基因分型。实验室化验的结果将与生活方式/饮食信息合并，并进行关联分析。这项拟议的项目将促进非洲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.