CROSS CULTURAL STUDY OF LUNG CANCER RISK AND INFLAMMATORY PATHWAY SNPS

肺癌风险和炎症途径 SNPS 的跨文化研究

• 批准号: 7620879
• 负责人: QIUYIN CAI
• 金额: $ 32.18万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7620879
• 关键词: Affect; Arachidonate 5-Lipoxygenase; Biological Markers; Blood; C-reactive protein; Cancer Detection; Carcinogens; Chinese People; Cohort Studies; Communities; Complement component C1s; Data; Dinoprostone; Doctor of Philosophy; Enzymes; Epidemiologic Studies; Epoprostenol; Equilibrium; Etiology; Evaluation; Funding; Genes; Genetic Markers; Genetic Polymorphism; Genotype; Haplotypes; Individual; Inflammation; Inflammatory; Leukotriene B4; Leukotriene C4; Leukotriene D4; Leukotriene E4; Leukotrienes; Lung; Malignant Neoplasms; Malignant neoplasm of lung; Measures; Mediator of activation protein; Metabolism; Nested Case-Control Study; Non-Steroidal Anti-Inflammatory Agents; PTGS1 gene; PTGS2 gene; Parents; Pathway interactions; Persons; Plasma; Polymorphism Analysis; Population; Predisposition; Principal Investigator; Production; Prospective Studies; Prostacyclin synthase; Prostaglandin Production; Prostaglandin-Endoperoxide Synthase; Prostaglandins; Prostaglandins E; Prostaglandins I; Protein C; Reproduction spores; Resources; Risk; Sampling; Screening procedure; Staging; Surveys; TNFRSF5 gene; Testing; Tobacco smoke; Urine; Variant; Women' s Health; arachidonate; cancer genetics; cancer risk; case control; cost; cyclooxygenase 1; cyclooxygenase 2; cysteinyl-leukotriene; cytokine; follow-up; innovation; lung carcinogenesis; novel; programs; urinary

While lung cancer is the most common fatal cancer in most populations of the world, the mechanisms by which tobacco smoke or other carcinogens cause lung cancer and the genetic factors that might enhance susceptibility are only partly understood. Several lines of evidence suggest, however, that inflammation may be a potential key pathway in lung carcinogenesis. Some of the most novel and promising findings from the Initial Vanderbilt Lung SPORE (P50 CA090949) were the demonstration of the potential utility of urinary metabolites of prostaglandin E2 (PGE2), a key mediator of the COX-2 pathway, as an inflammation biomarker and the detection of polymorphisms in the prostacyclin synthase (PTGIS) gene in assessing individual risk for lung cancer. We propose in this application to follow up these promising clues in a prospective study by examining the relations of the urinary PGE2 metabolite PGE-M and the prostacyclin (PGI2) metabolite PGI-M with the risk of lung cancer. Over the past ten years, we have established tremendous resources in two NCI-funded cohort studies, the US Southern Community Cohort Study (SCCS) (R01 CA092447) and the Chinese Shanghai Women's Health Study (SWHS) (R01 CA70867). In this application, we will take advantage of these valuable resources and propose a large nested case-control study to investigate: 1) the association of lung cancer risk and the urinary prostaglandin E2 metabolite (PGE-M) and urinary prostacyclin metabolite (PGI-M); and 2) the association of lung cancer risk with genetic polymorphisms of the genes involved in prostaglandin synthesis (PTGS2, PTGS1, PTGES, and PTGIS) and metabolism (15-PGDH). We will also investigate the association of lung cancer risk with plasma C-reactive protein (CRP), a sensitive marker of systemic inflammation, and the urinary leukotriences E4. Only a few cohort studies have collected both blood and urine samples at baseline to comprehensively measure relevant biomarkers. Therefore, the SCCS and SWHS, with their wealth of survey data and biospecimens, represent a unique opportunity to prospectively investigate the hypotheses proposed in this application. The proposed study is highly innovative and extremely cost-efficient. The study has great potentials to generate valuable biomarker information useful for identifying persons at high risk and amenable for screening for the detection of these cancers at an early, more curable stage.

虽然肺癌是世界上大多数人群中最常见的致命癌 烟草烟雾或其他致癌物引起肺癌以及可能增强的遗传因素 易感性仅部分理解。但是，有几条证据表明炎症可能 成为肺癌发生的潜在关键途径。一些最新颖，最有前途的发现 最初的范德比尔特肺孢子（P50 CA090949）是尿的潜在效用的证明 前列腺素E2的代谢物（PGE2），COX-2途径的关键介体，作为炎症 在评估前列环素合酶（PTGIS）基因中的生物标志物和多态性检测 肺癌的个人风险。我们在此应用中建议跟进这些有前途的线索 前瞻性研究通过检查尿液PGE2代谢物PGE-M和前列环蛋白的关系 （PGI2）具有肺癌风险的代谢产物PGI-M。在过去的十年中，我们建立了 美国南方社区队列研究（SCCS），两项NCI资助的队列研究中的巨大资源 （R01 CA092447）和中国上海妇女健康研究（SWHS）（R01 CA70867）。 在此应用程序中，我们将利用这些宝贵的资源，并提出一个大嵌套 病例对照研究要研究：1）肺癌风险与尿液前列腺素E2的关联 代谢产物（PGE-M）和前列环素代谢物（PGI-M）； 2）肺癌风险的关联 与参与前列腺素合成的基因的遗传多态性（PTGS2，PTGS1，PTGES和 PTGIS）和代谢（15-PGDH）。我们还将调查肺癌风险与血浆的关联 C反应蛋白（CRP），一种敏感的全身性炎症标志物和尿和白细胞E4。 只有少数队列研究在基线时同时收集了血液和尿液样本 测量相关的生物标志物。因此，SCC和SWHS凭借其丰富的调查数据以及 生物测量是一个独特的机会，可以预期研究此处提出的假设 应用。拟议的研究具有很高的创新性，并且具有极高的成本效益。这项研究很棒 产生有价值的生物标志物信息的潜力，可用于识别高风险和 可以在早期，更可治愈的阶段筛查这些癌症的检测。