A pilot study of statin therapy and risk of malignant glioma

他汀类药物治疗与恶性神经胶质瘤风险的初步研究

基本信息

批准号：
7915577
负责人：
Rose Kamyee Lai
金额：
$ 13.55万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-12 至 2013-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7915577
关键词：
Academic Medical Centers Adult Aftercare Anti-Inflammatory Agents Anti-inflammatory Area Brain Neoplasms Categories Cessation of life Chemoprevention Chemopreventive Agent Collaborations Diagnosis Disease Disease remission Dose Drug Exposure Drug usage Epidemiologic Studies Epidemiologist Epidemiology Etiology Event Explosion Frequencies Funding Genes Genetic Genetic Predisposition to Disease Genotype Glioblastoma Glioma Goals Guanosine Triphosphate Phosphohydrolases Hand Haplotypes Hospitals Hydroxymethylglutaryl-CoA reductase Incidence Individual Investigation Letters Life Local Therapy Malignant - descriptor Malignant Glioma Malignant Neoplasms Malignant neoplasm of brain Mentors Molecular Biology Molecular Genetics Multicenter Studies New Jersey New York Newly Diagnosed Non-Steroidal Anti-Inflammatory Agents Pathogenesis Pathway interactions Patients Persons Pharmaceutical Preparations Pharmacogenetics Pilot Projects Predisposition Presbyterian Church Prevention Preventive Property Recruitment Activity Research Research Training Risk Single Nucleotide Polymorphism Testing Therapeutic Training United States National Institutes of Health Work base cancer chemoprevention cardiovascular disorder prevention career case control chemotherapy clinical epidemiology cost effectiveness dosage drug candidate experience genetic epidemiology genetic profiling genetic risk factor high risk improved interest lectures meetings neoplasm registry neuro-oncology novel novel therapeutic intervention population based premature response rho tumor

项目摘要

DESCRIPTION (provided by applicant): Our understanding of the causation of brain tumors has been advancing slowly, because there are so few epidemiologists interested in the investigation of these diseases. My training in both clinical epidemiology and neuro-oncology has prepared me well for a career in brain tumor epidemiology. My immediate goals are to obtain further research training in brain tumor epidemiology, genetic epidemiology, cancer chemoprevention and population-based research through one-on-one mentoring, didactic lectures, seminars, meetings and hand-on experiences. In the next 5 years, I will seek opportunities to build a network of collaborators and to conduct pilot association studies to evaluate susceptibility factors in brain tumors. Initially, my research will take place at the New York Presbyterian Hospital, but after I establish a working relationship with the New Jersey Cancer Registry and the Brain Tumor Epidemiology Consortium, I will apply for funding to initiate population-based investigations and to collaborate with other epidemiologists in multicenter studies. My long term goal is to independently obtain NIH funding to examine the genetic susceptibility of brain tumors and to expand the potential of chemoprevention in these devastating diseases. Scientific Plan: I will recruit 200 cases and 400 frequency-matched controls at New York Presbyterian Hospital to evaluate the association between statin therapy and risk of malignant glioma. Based on these drugs' inhibition of the HMG-CoA reductase pathway, their immunomodulatory, anti-inflammatory and potentially anti-angiogenic effects, there may be an inverse association between the use of statins and risk of malignant glioma. In order to identify a genetic subset of individuals most likely to benefit from statins, I will also evaluate haplotype-tagged single nucleotide polymorphisms (htSNPs) of genes in the HMG-CoA reductase pathway, Rho and Ras GTPases as modifying factors for statins therapy. This strategy will allow the selection of those individuals with the right genetic profiles as drug candidates. Relevance: This will be one of the first studies that evaluates a chemopreventive approach in malignant glioma, and as such, will help to open up a new therapeutic approach in these diseases. Using an individual's genetic makeup to predict response to treatment may improve the cost effectiveness of using these drugs.

描述（申请人提供）：我们对脑肿瘤病因的认识进展缓慢，因为对研究这些疾病感兴趣的流行病学家太少了。我在临床流行病学和神经肿瘤学方面的培训为我在脑肿瘤流行病学领域的职业生涯做好了充分的准备。我的近期目标是通过一对一指导、教学讲座、研讨会、会议和实践经验，获得脑肿瘤流行病学、遗传流行病学、癌症化学预防和基于人群的研究方面的进一步研究培训。在接下来的5年里，我将寻求机会建立合作者网络并进行试点关联研究以评估脑肿瘤的易感因素。最初，我的研究将在纽约长老会医院进行，但在我与新泽西州癌症登记处和脑肿瘤流行病学联盟建立工作关系后，我将申请资金来启动基于人群的调查并与其他机构合作流行病学家进行多中心研究。我的长期目标是独立获得美国国立卫生研究院的资助，以检查脑肿瘤的遗传易感性，并扩大化学预防这些破坏性疾病的潜力。科学计划：我将在纽约长老会医院招募 200 个病例和 400 个频率匹配对照，以评估他汀类药物治疗与恶性胶质瘤风险之间的关联。基于这些药物对 HMG-CoA 还原酶途径的抑制、免疫调节、抗炎和潜在的抗血管生成作用，他汀类药物的使用与恶性神经胶质瘤的风险之间可能存在负相关。为了确定最有可能从他汀类药物中受益的个体遗传子集，我还将评估 HMG-CoA 还原酶途径、Rho 和 Ras GTPases 中基因的单倍型标记单核苷酸多态性 (htSNP) 作为他汀类药物治疗的修饰因素。这一策略将允许选择那些具有正确基因谱的个体作为候选药物。相关性：这将是评估恶性癌症化学预防方法的首批研究之一。神经胶质瘤，因此，将有助于开辟这些疾病的新治疗方法。使用个体的基因组成来预测对治疗的反应可能会提高使用这些药物的成本效益。