Cross cultural study of lung cancer risk and inflammatory pathway SNPs

虽然肺癌是世界上大多数人最常见的致命癌症，但其机制 烟草烟雾或其他致癌物导致肺癌的原因以及可能导致 对易感性的了解还只有一部分。然而，有几条证据表明，炎症可能会 是肺癌发生过程中潜在的关键途径。一些最新颖和最有希望的发现来自 最初的范德比尔特肺孢子(P50 CA090949)是尿液潜在用途的例证 前列腺素E2(PGE2)的代谢产物，COX-2途径的关键介质，作为一种炎症 生物标记物和前列环素合成酶基因多态性检测在疾病评估中的应用 个人患肺癌的风险。我们在这份申请中建议在一个 尿PGE_2代谢物PGE-M与前列环素关系的前瞻性研究 前列腺素I2(PGI2)代谢产物PGI-M与肺癌风险。在过去的十年里，我们已经建立了 NCI资助的两项队列研究--美国南部社区队列研究(SCCS)--的巨大资源 (R01 CA092447)和中国上海妇女健康研究(SWHS)(R01 CA70867)。 在本应用程序中，我们将利用这些宝贵的资源，并提出一个大型嵌套 病例对照研究：1)肺癌风险与尿前列腺素E_2的关系 代谢产物(PGE-M)和尿前列环素代谢产物(PGI-M)；以及2)与肺癌风险的关系 前列腺素合成相关基因(Ptgs2、PTGS1、PTGES和 PTG)和代谢(15-PGDH)。我们还将调查肺癌风险与血浆的关系。 C-反应蛋白(C-反应蛋白)，全身炎症的敏感标志，和尿白细胞营养素E4。 只有少数几项队列研究在基线时收集了血液和尿样，以全面 测量相关的生物标志物。因此，SCCS和SWHS凭借其丰富的调查数据和 生物制品，代表了一个独特的机会来前瞻性地研究本研究中提出的假设。 申请。拟议的研究具有很高的创新性和极高的成本效益。这项研究有很大的意义 有潜力产生有价值的生物标志物信息，有助于识别高危人群和 适合在早期、更可治愈的阶段进行筛查以发现这些癌症。

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.