SNPs in Lung Cancer Risk and Therapeutic Response

SNP 与肺癌风险和治疗反应的关系

• 批准号: 6764123
• 负责人: Effie W Petersdorf
• 金额: $ 17.3万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6764123
• 关键词: biomarker; cancer risk; clinical research; genetic markers; genetic polymorphism; genetic screening; genotype; human subject; lung neoplasms; polymerase chain reaction; single nucleotide polymorphism; technology /technique development

DESCRIPTION (provided by applicant): Lung cancer is the greatest single cause of cancer mortality worldwide. Although environmental risk factors have been well defined, smoking prevalence has not declined. Available screening tests for early detection of lung cancer have not lowered overall morbidity and mortality from lung cancer. With the completion of the prototype sequence by the Human Genome Project, information on single nucleotide polymorphisms (SNPs) encoded in cytokine genes has become available. In particular, cytokine gene polymorphisms (CGPs) have recently been shown to be promising predictive markers in several solid tumor model systems and in stem cell transplantation. In the lung cancer model, we hypothesize that CGPs interact with inflammatory stimuli, including tobacco or asbestos exposure, to promote progression to lung cancer. If CGPs modulate risk of lung cancer, then screening tools can be developed to assess cancer risk and to detect high-risk patients. If CGPs correlate with outcome of lung cancer therapy, then the use of CGPs to predict response to therapy and guide clinical interventions may be feasible. These hypotheses are eminently testable in large clinical populations of cancer patients and controls for whom extensive clinical and phenotype data is available. To this end, we propose to collaborate with the CARET trial repository (NIH grant CA63673) to access blood samples from lung cancer patients and cancer-free individuals. Our application is an R21 exploratory project in response to PA-01-015 in which we will develop PCR arrays and retrospectively characterize 1,212 study individuals for a panel of 20 CGPs (Specific Aim 1). We will determine whether certain SNPs correlate with the presence of lung cancer (Specific Aim 2), and whether certain SNPs are associated with survival among lung cancer patients (Specific Aim 3). The information will be highly relevant to the design of larger confirmatory clinical studies in the future. Furthermore, the array methodology can be directly and immediately translated to high-throughput population-based testing. If CGPs can be identified as predictive risk markers or prognostic markers in lung cancer, then screening methods can be developed to screen for high-risk individuals before the development of lung cancer; furthermore, if SNPs correlate with clinical response, then use of SNPs genotyping to guide therapeutic interventions can be incorporated into the management care plan of the patient.

描述（由申请人提供）：肺癌是全球癌症死亡率的最大原因。尽管环境风险因素已经很好地定义，但吸烟率尚未下降。可用的筛查测试可早期检测到肺癌的疾病，尚未降低肺癌的总体发病率和死亡率。随着人类基因组项目的原型序列完成，有关细胞因子基因中编码的单核苷酸多态性（SNP）的信息已获得。特别是，最近已证明细胞因子基因多态性（CGP）在几种实体瘤模型系统和干细胞移植中是有希望的预测标记。在肺癌模型中，我们假设CGP与包括烟草或石棉暴露在内的炎症刺激相互作用，以促进肺癌的发展。如果CGP调节肺癌的风险，则可以开发筛查工具来评估癌症风险并检测高危患者。如果CGP与肺癌治疗的结果相关，则使用CGP来预测对治疗的反应和指导临床干预措施。这些假设在大量的癌症患者和对照组中可以很好地检验，并为其提供广泛的临床和表型数据。为此，我们建议与Caret试验存储库（NIH Grant CA63673）合作，以获取来自肺癌患者和无癌个体的血液样本。我们的应用程序是R21探索性项目，响应PA-01-015，我们将开发PCR阵列，并回顾性地表征了20 CGP的1,212个研究个体（特定的AIM 1）。我们将确定某些SNP是否与肺癌的存在相关（特定AIM 2），以及某些SNP是否与肺癌患者的生存有关（特定AIM 3）。该信息将来将与更大的确认性临床研究的设计高度相关。此外，阵列方法可以直接并立即转化为基于人群的高通量测试。如果可以将CGP鉴定为肺癌中的预测风险标记或预后标记，则可以在肺癌发展之前开发筛查方法来筛查高危个体。此外，如果SNP与临床反应相关，则可以将SNP基因分型用于指导治疗干预措施，并将其纳入患者的管理护理计划中。