Oxidative Stress, DNA Repair & Colorectal Adenoma Risk

氧化应激、DNA 修复

• 批准号: 7618721
• 负责人: Michael Goodman
• 金额: $ 28.62万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7618721
• 关键词: Address; Adenomatous Polyps; Affect; Antioxidants; Arachidonic Acids; Attention; Base Excision Repairs; Biological; Biological Markers; Blood; Blood specimen; Body fat; C-reactive protein; Carotene; Carotenoids; Case-Control Studies; Chronic; Collection; Colon Carcinoma; Colonoscopy; Colorectal Adenoma; Colorectal Cancer; Colorectal Neoplasms; DNA Repair; DNA Repair Enzymes; DNA Repair Gene; Data; Data Collection; Diet; Diet Habits; Disease; ERCC5 gene; Endogenous Factors; Epidemiologic Studies; Equilibrium; Event; Excision; Family history of; Ferritin; Food; Frequencies; Future; GSTM1 gene; GSTT1 gene; Genes; Genetic; Genetic Polymorphism; Genetic Variation; Genotype; Goals; Haplotypes; Human; Inflammation; Inflammatory Response; Intake; Interview; Iron; Isomerism; Isoprostanes; Laboratories; Leukocytes; Life Style; Lipid Peroxidation; Lipids; Logistic Regressions; Lutein; Mails; Manganese Superoxide Dismutase; Measures; Meat; Mediating; Medical Records; Minnesota; Modeling; Modification; North Carolina; Nuclear; OGG1 gene; Oxidative Stress; Oxidative Stress Pathway; PTGS2 gene; Parents; Participant; Pathogenesis; Pathology; Patients; Pharmaceutical Preparations; Phenotype; Physical activity; Plasma; Play; Polyps; Process; Property; Protocols documentation; Questionnaires; Reactive Oxygen Species; Recording of previous events; Regulation; Research Design; Risk; Role; Sample Size; Sampling; Serum; Single Nucleotide Polymorphism; Testing; Tocopherols; Work; XRCC1 gene; adenoma; alpha Tocopherol; base; case control; cyclooxygenase 1; dietary carcinogenesis; human APEX1 protein; lifestyle factors; lycopene; oxidative DNA damage; oxidative damage; reproductive

DESCRIPTION (provided by applicant): The objective of the proposed study is to examine the association between colorectal adenoma and determinants of oxidative stress including dietary habits, serum ferritin (marker of iron intake), biomarkers of oxidative damage, serum antioxidant levels, as well as genetic variation in antioxidant, arachidonic acid- metabolizing (inflammation-related) and DNA repair enzymes. The proposed scope of work (referred to as the 'New Study') is limited to laboratory and statistical analyses using biological samples and questionnaire data from a two previously conducted, and methodologically very similar, colonoscopy-based case-control studies of sporadic colorectal adenoma (Parent studies): one conducted in North Carolina and another conducted in Minnesota. None of the analyses proposed for the New Study were part of the Parent Studies design and scope. Cases included in the Parent Studies were pathology-confirmed, incident adenomatous polyp patients, and controls were patients with no previous history of adenomatous polyps who underwent colonoscopy and were found to be free of adenomatous polyps. The final sample size included 778 cases and 920 controls. All participants completed mailed questionnaires, which included information on family history of polyps or colon cancer, dietary information (through use of a Willett Food Frequency Questionnaire), physical activity, reproductive variables, body fat distribution, and their reason(s) for and the sequence of events leading to colonoscopy. Blood was drawn, processed by various protocols, and stored as Buffy coats, nuclear pellets, serum, and plasma at -86¿C. The laboratory analysis for the New Study will include measuring biomarkers of oxidative DNA damage (8-OHdG) and lipid peroxidation (isoprostanes), levels of lipid-soluble carotenoids and tocopherols (antioxidants) and serum ferritin (marker of potentially pro- oxidant iron intake), and genotyping for polymorphisms of five antioxidant genes (GSTT1, GSTM1, MnSOD, EC-SOD, and GPX1) and five arachidonic acid-metabolizing genes (COX-2, LOX-5, LOX-12, LOX15 and PPAR-y). We will also evaluate the SNPs of the main genes involved in DNA base excision repair including OGG1, APE1, XRCC1, ERCC5 and several others. The resulting data will be analyzed using multivariate unconditional logistic regression models. Particular attention will be paid to identification of potential gene- gene, gene-lifestyle, and gene-phenotype interactions.

描述（由申请人提供）：拟议研究的目的是检查结直肠腺瘤与氧化应激决定因素之间的关联，包括饮食习惯、血清铁蛋白（铁摄入标志物）、氧化损伤生物标志物、血清抗氧化剂水平以及作为抗氧化剂、花生四烯酸代谢（炎症相关）和 DNA 修复酶的遗传变异，拟议的工作范围（称为“新研究”）是。仅限于使用生物样本和问卷数据进行实验室和统计分析，这些数据来自先前进行的两项在方法上非常相似的基于结肠镜检查的散发性结直肠腺瘤病例对照研究（家长研究）：一项在北卡罗来纳州进行，另一项在明尼苏达州进行。新研究的拟议分析均不属于母体研究设计和范围的一部分，母体研究中包含的病例是经病理证实的腺瘤性息肉患者，对照组是既往没有腺瘤病史的患者。最终样本量包括 778 例病例和 920 名对照，所有参与者均填写了邮寄问卷，其中包括有关息肉或结肠癌家族史的信息、饮食信息（通过使用问卷调查）。威利特食物频率问卷）、体力活动、生殖变量、身体脂肪分布及其原因和导致结肠镜检查的事件顺序被抽取，通过各种方案进行处理，并存储为。 -86° 的血沉棕黄层、核颗粒、血清和血浆C. 新研究的实验室分析将包括测量氧化 DNA 损伤 (8-OHdG) 和脂质过氧化（异前列腺素）的生物标志物、脂溶性类胡萝卜素和生育酚（抗氧化剂）以及血清铁蛋白（潜在促氧化剂的标志物）的水平。铁摄入量），以及五种抗氧化基因（GSTT1、GSTM1、MnSOD、 EC-SOD和GPX1）和五个花生四烯酸代谢基因（COX-2、LOX-5、LOX-12、LOX15和PPAR-y）我们还将评估参与DNA碱基切除修复的主要基因的SNP。包括 OGG1、APE1、XRCC1、ERCC5 等 将使用多元无条件逻辑回归模型对所得数据进行分析。潜在的基因-基因、基因-生活方式和基因-表型相互作用。

项目成果

DNA base excision repair genetic risk scores, oxidative balance, and incident, sporadic colorectal adenoma.

DNA 碱基切除修复遗传风险评分、氧化平衡和事件、散发性结直肠腺瘤。

• DOI: 10.1002/mc.22620
• 发表时间: 2017
• 期刊: Molecular carcinogenesis
• 影响因子: 4.6
• 作者: Wang,Tengteng;Goodman,Michael;Sun,YanV;Thyagarajan,Bharat;Gross,Myron;Bostick,RoberdM
• 通讯作者: Bostick,RoberdM