Infection and Inflammation in Adult Gliomas

职位描述(申请人提供)：我的职业目标是成为分子流行病学领域的一名独立和成熟的研究员，拥有与癌症病因和预防相关的病毒和炎症因子方面的专业知识。这个目标建立在我之前的流行病学方法和病毒学培训的基础上，但需要进一步的免疫学和生物统计学培训。在这次培训结束后，我将拥有专业知识和初步数据，以便为我在癌症流行病学和预防方面的独立研究提供资金。我已经制定了一个全面的教育和指导计划。我的教育计划将在免疫学和分子流行病学的生物统计学方法领域提供密集的指导。我已经挑选了四位导师，他们将监督我的培训和研究的具体部分。Melissa Bondy博士将在分子和遗传流行病学以及癌症预防方面指导我，并将指导我的职业发展；Thomas Albrecht博士将在免疫学和病毒学方面提供指导；Charles Cobbs博士将提供脑部解剖学、生理学和神经肿瘤学方面的专业知识；Kim-Ann Do博士将监督生物统计学方法的开发和应用，尤其是与流行病学研究中微阵列使用相关的方法。我的研究计划将重点检查病毒和免疫因素对胶质瘤风险和患者预后的影响。我建议在梅丽莎·邦迪博士的指导下，利用现有病例对照研究(R01CA070917)的流行病学和遗传标记数据和临床标本。这项研究目前包括1200多例，主要是高加索人，胶质瘤病例和对照，在性别、年龄和种族上匹配。我的研究目标是检查病毒、免疫学和遗传因素对成人胶质瘤风险和患者预后的影响。本研究的具体目的是：1.评估脑胶质瘤患者和正常对照个体对巨细胞病毒感染和免疫功能的影响。这将为父母赠款现有的关于感染和免疫功能的遗传和流行病学数据增加重要的分子数据。这对于验证自我报告的流行病学数据很重要。2.利用流行病学和遗传学资料以及感染和免疫功能的标志物，对脑胶质瘤的风险进行病例对照分析。我将使用多元Logistic回归的方法来模拟神经胶质瘤风险作为遗传、分子和流行病学变量的函数。在现有样本量的情况下，我将适当地纳入基因-环境和基因-基因相互作用。3.确定感染和免疫反应的标志物是否与脑胶质瘤患者的临床结局和总生存期有关。我将使用COX比例风险回归来建模与治疗结果和患者总存活率相关的因素。

DESCRIPTION (provided by applicant): My career goal is to become an independent and established researcher in molecular epidemiology with expertise in viral and inflammatory factors related to cancer etiology and prevention. This goal builds upon my previous training in epidemiologic methods and virology, but requires further training in immunology and biostatistics. At the end of this training period, I will have the expertise and preliminary data to submit for funding of my independent research in cancer epidemiology and prevention. I have developed a comprehensive education and mentoring plan. My education plan will provide intensive instruction in the areas of immunology, and biostatistical methods for molecular epidemiology. I have chosen four mentors who will supervise specific portions of my training and research. Dr. Melissa Bondy will mentor me in molecular and genetic epidemiology and cancer prevention and will guide my career development; Dr. Thomas Albrecht provide guidance in immunology and virology; Dr. Charles Cobbs will provide expertise in brain anatomy, physiology, and neuro-oncology; and Dr. Kim-Ann Do will supervise the development and application of biostatistical methods, especially as they related to the use of microarrays in epidemiologic research. My research proposal will focus on examining viral and immunologic factors in glioma risk and patient outcome. I propose to capitalize on the availability of epidemiologic and genetic marker data and clinical specimens from an existing case-control study (R01CA070917) under the direction of Dr. Melissa Bondy. This study currently includes over 1200, mostly Caucasian, glioma cases and controls, matched on sex, age, and ethnicity. My research goal is to examine viral, immunologic, and genetic factors in adult glioma risk and patient outcome. The specific aims are: 1. To assess markers of individual variation to HCMV infection and immune function in glioma cases and controls. This will add important molecular data to the existing genetic and epidemiologic data on infection and immune function from the parent grant. This is important in validating the self-reported epidemiologic data. 2. To perform a case-control analysis of glioma risk utilizing epidemiologic and genetic data and markers of infection and immune function. I will employ the methods of multiple logistic regression to model glioma risk as a function of genetic, molecular, and epidemiologic variables. I will incorporate gene-environment and gene-gene interactions as appropriate given the sample size available. 3. To Determine if markers of infection and immune response are associated with clinical outcome and overall survival in glioma patients. I will employ Cox proportional hazards regression to model factors associated with treatment outcome and overall patient survival.