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Diet, Activity, and Lifestyle as a Risk Factor for Colorectal Cancer

饮食、活动和生活方式是结直肠癌的危险因素

基本信息

批准号：
8120975
负责人：
Martha L SLATTERY
金额：
$ 89.95万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
1991
资助国家：
美国
起止时间：
1991-03-15 至 2013-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8120975
关键词：
1-Phosphatidylinositol 3-Kinase AKT1 gene Affect Age Androgens Anti-Inflammatory Agents Anti-inflammatory Antioxidants Area Aspirin Biological Biological Assay Body mass index Cancer Etiology Candidate Disease Gene Case-Control Studies Code Colon Colon Carcinoma Colorectal Cancer Complex Critical Pathways DNA-Binding Proteins Data Databases Development Diet Dietary Factors Dietary Fats Dietary intake Disease Pathway Drug usage Energy Intake Energy Metabolism Environment Environmental Risk Factor Epidemiologic Studies Epidemiology Estrogens Etiology FRAP1 gene Fat Body Fatty acid glycerol esters Gene Mutation Gene Targeting Genes Genetic Genetic Polymorphism Genetic Predisposition to Disease Genetic Transcription Genetic Variation Genotype Glycemic Index Grant Growth Factor Oncogenes Haplotypes Health IGF1 gene IGFBP3 gene IKBKB IL4 gene IL6 gene IL8 gene IRS1 gene IRS2 gene Ibuprofen In Vitro Inflammation Inflammation Process Inflammatory Insulin Interferon Type II Interleukin-1 Interleukin-10 Knowledge Lead Life Style MAPK8 gene Malignant Neoplasms Measures Mediator of activation protein Metabolic Metabolic Pathway Metabolism Mitogen-Activated Protein Kinases Molecular Mutation NF-kappa B Obesity PIK3CG gene PTEN gene PTGS1 gene PTGS2 gene Pathway interactions Pharmaceutical Preparations Pharmacotherapy Phenotype Phosphotransferases Physical activity Play Process Proteins Proto-Oncogene Proteins c-akt Recombinant Proteins Recommendation Rectal Cancer Regulation Relative Risks Reporter Reproduction Research Personnel Resources Risk Risk Factors Role STAT protein STAT1 gene STAT6 gene STK11 gene Sampling Signal Pathway Signal Transduction Site Somatic Mutation Statistical Methods TP53 gene TSC1 gene TSC2 gene Techniques Technology Testing Tuberous sclerosis protein complex Tumor Necrosis Factor-alpha Tumor Suppressor Proteins Untranslated Regions Validation Vascular Endothelial Growth Factors Work base cancer risk carcinogenesis cost cost effective cytokine data acquisition dietary antioxidant disorder risk energy balance epidemiologic data flexibility gene interaction human FRAP1 protein human tissue improved indexing inhibitor/antagonist insight insulin-related factor knowledge base lifestyle factors neoplastic cell novel population based prevent programs sex tumor validation studies

项目摘要

DESCRIPTION (provided by applicant): Colorectal cancer has many diet and lifestyle factors that contribute to the etiology. Data suggest that differences in etiology exist by tumor site, age, and sex, and that certain exposures modify the effects of others, indicating the importance of various diet and lifestyle factors in certain environments. Major factors that modify the effects of other risk factors are'use of aspirin and ibuprofen-type drugs. Our previous data have shown that NSAIDs interact with a variety of diet and lifestyle factors, including dietary fat, BMI, insulin- related genes, and estrogen. We hypothesize that genetic variation in an inflammation-related signaling pathway and in a pathway where inflammation, insulin and estrogen converge (designated as a metabolic signaling pathway) will most likely have implications for disease risk. We propose to study two pathways which have not previously been studied with colorectal cancer. We utilize data previously collected on 2780 incident cases of colorectal cancer and 3025 population-based controls to obtain a better understanding of the inter-relationship between inflammation, insulin, and estrogen. We examine known functional polymorphisms and evaluate haplotypes in candidate genes in an inflammation-related pathway (IL6, IL8, IL10, NFKB, TNF-A, IL4, IL1, ILIRA and IFNG) and genes located at key junctions where other cellular signaling pathways converge which we describe as a metabolic signaling pathway (SOC1, SOC2, AKT, FRAP1 (mTOR), TSC1, TSC2, P13K, LKB, AMP, PTEN, S6K.VEGF, STAT1, STAT6, JNK1, and pSSMAPK). We will test associations between genetic polymorphisms and haplotypes of these genes with colorectal cancer. We will evaluate the interaction of these genes with NSAIDs/aspirin, estrogen, BMI, dietary fat, antioxidants, and physical activity. We will evaluate associations of these polymorphisms/haplotypes with specific types of tumor mutations. We will utilize statistical methods to gain insight into how these genes relate to specific disease pathways and how genes inter-relate along these pathways. We include test of functionality for all genes and SNPs identified as being assocatied with CRC and we will validate study findings using statistical techniques that allow for test and validation. Identification of polymorphisms or haplotypes that are relevant to colorectal cancer will advance our understanding of etiology, may lead to specific health recommendations, and can identify targets for drug therapy.

描述(申请人提供)：结直肠癌有许多饮食和生活方式的因素，有助于病因。数据表明，肿瘤部位、年龄和性别在病因上存在差异，某些暴露会改变其他因素的影响，表明各种饮食和生活方式因素在特定环境中的重要性。影响其他风险因素影响的主要因素是阿司匹林和布洛芬类药物的使用.我们之前的数据表明，非甾体抗炎药与各种饮食和生活方式因素相互作用，包括饮食脂肪、BMI、胰岛素相关基因和雌激素。我们假设，炎症相关信号通路以及炎症、胰岛素和雌激素汇聚的通路(称为代谢信号通路)中的遗传变异最有可能与疾病风险有关。我们建议研究两个以前没有研究过的结直肠癌途径。我们利用之前收集的2780例结直肠癌病例和3025例人群对照的数据来更好地了解炎症、胰岛素和雌激素之间的相互关系。我们在炎症相关途径(IL6、IL8、IL10、NFKB、TNF-A、IL4、IL1、ILIRA和IFNG)和位于其他细胞信号通路汇聚的关键连接处的基因(SOC1、SOC2、AKT、FRAP1(MTOR)、TSC1、TSC2、P13K、LKB、AMP、PTEN、S6K.VEGF、STAT1、STAT6、JNK1和pSSMAPK)中检测已知的功能多态并评估候选基因的单倍型。我们将测试这些基因的遗传多态和单倍型与结直肠癌的关系。我们将评估这些基因与非甾体抗炎药/阿司匹林、雌激素、体重指数、膳食脂肪、抗氧化剂和体力活动的相互作用。我们将评估这些多态/单倍型与特定类型的肿瘤突变的相关性。我们将利用统计方法来深入了解这些基因如何与特定的疾病途径相关，以及基因如何沿着这些途径相互联系。我们包括对所有与CRC相关联的基因和SNP的功能进行测试，我们将使用允许测试和验证的统计技术来验证研究结果。识别与结直肠癌相关的多态或单倍型将促进我们对病因学的理解，可能导致特定的健康建议，并可以确定药物治疗的靶点。