Molecular epidemiology of lung cancer

描述(申请人提供)：Anil Vachani，医学博士，宾夕法尼亚大学医学院肺、过敏和重症监护科成员，生物统计和流行病学系教员。该奖项的职业发展部分包括宾夕法尼亚大学癌症流行病学主任蒂莫西·雷贝克博士的指导工作，以及分子流行病学方面的高级课程。还将获得进行精心设计的分子流行病学研究所需的实验室技术方面的额外培训。这一授课和应用指导计划将扩展Vachani博士的培训，将直接适用于及时完成他的研究提案，并将为他成为肺癌分子流行病学的独立研究员提供必要的基础。这项拟议研究的目的是评估候选基因多态在决定肺癌患者预后中的作用。肺癌是世界范围内主要癌症发病率和死亡率的最常见原因。目前，预测手术切除肿瘤患者预后的能力是有限的。虽然手术治疗可能是治愈的，但包括与免疫系统相关的机制在内的许多变量可能会影响肺癌切除患者的复发风险和生存。瓦查尼博士项目背后的假设是，较高水平的免疫耐受性和逃逸在非小细胞肺癌的预后中起着关键作用。更具体地说，我们将测试免疫抑制基因的遗传变异与非小细胞肺癌患者肿瘤特征和预后的关系。还将评估基因-基因相互作用和更高阶的相互作用。该项目的结果可能为肺癌进展中涉及的免疫机制提供有价值的见解，并允许识别可能受益于辅助治疗的患者，特别是新的免疫治疗策略。

DESCRIPTION (provided by applicant): Anil Vachani, M.D. is a member of the Pulmonary, Allergy, and Critical Care Division at the University of Pennsylvania School of Medicine and is a faculty-fellow in the Department of Biostatistics and Epidemiology. The career development component of the award proposed herein includes a preceptorship with Dr. Timothy Rebbeck, Director of Cancer Epidemology at Penn, and advanced coursework in molecular epidemiology. Additional training will be obtained in laboratory techniques necessary for the conduct of well designed molecular epidemiologic studies. This program of didactic and applied instruction will extend Dr. Vachani's training, will be directly applicable to timely completion of his research proposal, and will provide him with the necessary foundation to become an independent investigator in the molecular epidemiology of lung cancer. The goal of the proposed research is to evaluate the role of candidate genetic polymorphisms in the determination of outcomes among patients with lung cancer. Lung cancer is the most common worldwide cause of major cancer incidence and mortality. At present, the ability to predict outcome in patients with surgically resected tumors is limited. Although surgical therapy may be curative, a number of variables including mechanisms related to the immune system may influence the risk of recurrence and survival in patients with resected lung cancer. The hypothesis underlying Dr. Vachani's project is that higher levels of immune tolerance and escape play a key role in the outcome of NSCLC. More specifically, we will test the association of genetic variation in immunosuppressive genes with tumor characteristics and outcomes in patients with NSCLC. Gene-gene interactions and higher order interactions will also be evaluated. Results from this project may provide valuable insight into immune mechanisms involved in lung cancer progression and allow for the identification of patients that may benefit from adjuvant therapy, particularly novel immunotherapeutic strategies.