Oxidative Stress, DNA Repair & Colorectal Adenoma Risk

氧化应激、DNA 修复

• 批准号: 7259145
• 负责人: Michael Goodman
• 金额: $ 29.59万
• 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/7259145
• 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; Score; Serum; Single Nucleotide Polymorphism; Superoxide Dismutase; Testing; Tocopherols; Work; XRCC1 gene; adenoma; alpha Tocopherol; base; case control; cyclooxygenase 1; dietary carcinogenesis; glutathione S-transferase M1; human APEX1 protein; lycopene; oxidative DNA 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（由适用提供）：拟议的研究的目的是检查有色腺瘤和确定氧化应激之间的关联，包括饮食习惯，血清铁蛋白（铁的摄入量标志），氧化损伤的生物标志物，血清抗氧化剂水平的生物标志物，抗氧化剂的遗传性抗氧化剂含量和芳族酸 - 含量 - 芳族酸性含量（降低）。提出的工作范围（称为“新研究”）仅限于实验室和统计分析，使用先前进行的两个和方法上非常相似的，基于结肠镜检查的病例对照研究的生物样品和问卷数据，对零星腺瘤的病例对照研究（父母研究）（父母研究）：在北卡罗来纳州进行了一次进行的指导。对新研究提出的分析都不是父母研究设计和范围的一部分。父母研究中包括的病例是病理确认的，入射的腺瘤性息肉患者，对照组是没有先前接受结肠镜检查的腺瘤息肉病史的患者，被发现没有腺瘤息肉。最终样本量包括778例和920个对照。所有参与者都填写了邮寄问卷，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Willett食品频率问卷），体育活动，生殖变量，体内脂肪分布及其原因以及导致结肠镜检查的事件的序列。抽血，通过各种方案处理，并以-86€C。作为Buffy毛皮，核颗粒，血清和血浆。铁蛋白（潜在的促氧化铁摄入量的标记）和五种抗氧化基因（GSTT1，GSTM1，MNSOD，EC-SOD和GPX1）和五种芳基二酮二酮酸 - 代谢基因（COX-5，LOX-5，LOX-5，LOX-5，LOX，LOX，LOX，LOX，LOX15）和PPAR-15和PPAR-PAR-YX15和PPAR-YX-5--------------------------抗氧化基因（GSTT1，GSTM1，MNSOD，EC-SOD和GPX1）的基因分型。我们还将评估参与DNA碱基惊喜维修的主要基因的SNP，包括OGG1，APE1，XRCC1，ERCC5等。将使用多元无条件逻辑回归模型分析所得数据。特别注意鉴定潜在基因，基因生物和基因 - 表型相互作用。