MOLECULAR EPIDEMIOLOGY OF LUNG CANCER

肺癌的分子流行病学

• 批准号: 7472529
• 负责人: CHU CHEN
• 金额: $ 51.49万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-10 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7472529
• 关键词: Accounting; Age; All-Trans-Retinol; American Cancer Society; Antioxidants; Aromatic Polycyclic Hydrocarbons; Asbestos; Ascorbic Acid; Base Excision Repairs; Behavioral; Bioinformatics; Blood specimen; Brassicaceae; Cancer Etiology; Carcinogens; Carotene; Carotenoids; Cessation of life; Cost Analysis; DNA; DNA Adduction; DNA Adducts; DNA Damage; DNA Repair; DNA Repair Enzymes; DNA Repair Gene; DNA Repair Pathway; DNA Resequencing; DNA glycosylase; DNA-Directed DNA Polymerase; Databases; Development; Diagnosis; Diet; Dietary Factors; Dietary History; Dietary intake; Disease; ERCC2 gene; ERCC3 gene; ERCC5 gene; Enrollment; Enzymes; Epidemiologist; Etiology; Excision; Food; Freezing; Frequencies; Fruit; Generations; Genes; Genetic; Genetic Polymorphism; Genetic Variation; Genome; Genotype; Haplotypes; Histologic; Histology; Individual; Intake; Intervention; Investigation; Lead; Ligase; Light; Lung; Malignant Neoplasms; Malignant neoplasm of lung; Molecular; Molecular Epidemiology; Nested Case-Control Study; Nitrosamines; Nucleotide Excision Repair; Numbers; Nutrient; Oxidative Stress; POLB gene; Participant; Pathway interactions; Persons; Play; Population Study; Predisposition; Prevalence; Proteins; Questionnaires; Race; Randomized; Reactive Oxygen Species; Records; Research; Research Personnel; Resources; Risk; Risk Factors; Role; Rosacea; Rosaceae; Sampling; Scaffolding Protein; Screening procedure; Single Nucleotide Polymorphism; Smoke; Smoker; Smoking; Smoking History; Smoking Status; Subgroup; Surgical incisions; Testing; Tobacco; Tobacco smoke; Tobacco-Associated Carcinogen; United States; Variant; Vegetables; Vitamin A; Vitamin E; Whole Blood; Woman; XRCC1 gene; adduct; base; cancer risk; case control; cruciferous vegetable; efficacy trial; endonuclease; enzyme activity; follow-up; fruits and vegetables; helicase; human APEX1 protein; insight; lung cancer prevention; lung carcinogenesis; member; men; nuclease; programs; repaired; sex; statistics; tobacco exposure; tool; tumor

DESCRIPTION (provided by applicant): Tobacco smoke is the major cause of lung cancer, the most common type of fatal cancer worldwide. A possible means by which tobacco smoke exerts its carcinogenic effect is the DNA damage produced by the generation of reactive oxygen species and the formation of DNA adducts. Since the majority of persons who smoke tobacco do not develop lung cancer, it is possible that those who do develop this disease have a relatively poor capacity to repair the DNA damage that results from smoking. In a nested case-control study, we plan to determine whether polymorphisms of enzymes involved in the repair of smoking-induced DNA damage, namely those from the base excision (BER) and nucleotide excision repair (NER) pathways, are associated with risk of lung cancer. We propose to genotype the functional single nucleotide polymorphisms (SNPs) as well as tagging SNPs of 25 DNA repair genes (a total of 331 polymorphisms), that have been resequenced by the Seattle Variation Discovery Resource for the Environmental Genome Project. The lung cancer cases (n = 900) and controls (n = 1800) for the proposed study will come from the participants in the Carotene and Retinol Efficacy Trial (CARET) of lung cancer prevention. Genotyping of cases and controls will utilize DNA extracted from frozen whole blood samples. Detailed quantitative information on smoking and dietary history (using a food frequency questionnaire), obtained prior to the diagnosis of lung cancer, is available through CARET records. Cases and controls will be compared with respect to the prevalence of putative "high risk" genotypes, alone and in combination with other putative "high risk" genotypes within each pathway and in the two pathways combined. Analyses will also examine whether inferred haplotypes and their combinations are associated with risk. We will assess whether associations differ by histologic subtypes and sex. Results will be interpreted with multiple comparisons taken into account. The proposed study has sufficient statistical power to identify interactions between some of the high-risk genotypes/haplotypes, and to investigate whether the risk associated with a particular genotype/haplotype varies by other risk factors, such as smoking intensity and recency, and dietary factors, such as intake of antioxidant-rich fruits and vegetables (e.g. Rosaceae fruits and Cruciferae vegetables), and food-derived nutrients (e.g. carotenoids, vitamin C, and vitamin E).

描述（由申请人提供）：烟草烟雾是肺癌的主要原因，肺癌是全世界最常见的致命癌症类型。烟草烟雾发挥其致癌作用的一个可能途径是活性氧的产生和DNA加合物的形成所造成的DNA损伤。由于大多数吸烟者不会患上肺癌，因此患上这种疾病的人修复吸烟造成的 DNA 损伤的能力可能相对较差。在一项巢式病例对照研究中，我们计划确定参与修复吸烟引起的 DNA 损伤的酶的多态性，即来自碱基切除 (BER) 和核苷酸切除修复 (NER) 途径的酶的多态性是否与以下风险相关：肺癌。我们建议对功能性单核苷酸多态性 (SNP) 以及 25 个 DNA 修复基因（总共 331 个多态性）的标记 SNP 进行基因分型，这些基因已由西雅图环境基因组项目变异发现资源重新测序。拟议研究的肺癌病例 (n = 900) 和对照 (n = 1800) 将来自预防肺癌的胡萝卜素和视黄醇功效试验 (CARET) 的参与者。病例和对照的基因分型将利用从冷冻全血样本中提取的 DNA。在诊断肺癌之前获得的有关吸烟和饮食史（使用食物频率调查问卷）的详细定量信息可通过 CARET 记录获得。将比较病例和对照的假定“高风险”基因型的患病率，单独的以及与每个途径内和两个途径组合中的其他假定“高风险”基因型组合的患病率。分析还将检查推断的单倍型及其组合是否与风险相关。我们将评估关联是否因组织学亚型和性别而异。将通过多重比较来解释结果。拟议的研究具有足够的统计能力来识别一些高风险基因型/单倍型之间的相互作用，并调查与特定基因型/单倍型相关的风险是否因其他风险因素而变化，例如吸烟强度和新近度以及饮食因素，例如摄入富含抗氧化剂的水果和蔬菜（例如蔷薇科水果和十字花科蔬菜），以及食物来源的营养素（例如类胡萝卜素、维生素C和维生素E）。