GENETIC SUSCEPTIBILITY TO LUNG CANCER

越来越明显的是，肺癌的病因 涉及环境和遗传因素的组合，以及 个体的遗传易感性可能会有很大的差异 烟草等致癌物质。这个项目的主要目标是 确定遗传倾向于非常高风险的个人。 为此，我们将建立一个以人群为基础的肺癌登记系统 由大约200万人组成。我们将收集人口统计数据， 家族史，以及肺癌患者和家庭的吸烟数据 会员。血液样本的采集和储存将与 孢子病理学资源核心(核心B)。我们将实行种族隔离 对这些家系的分析以符合遗传和环境假设 确定了表征肺的家族聚集性的最佳模型 癌症(目标1)。在这样做的过程中，我们还将确定特定的家庭 这将为后续的遗传连锁和候选基因提供有用的信息 学习。先证者的临床特征可能与 家庭成员患癌症风险的增加将得到确定。敏感度 外周血淋巴细胞DNA对诱变剂诱导的染色单体断裂的影响 将在无家人的肺癌患者中进行评估 肺癌病史(目标2)。此外，我们还将比较模式 家族性肺癌患者等位基因缺失的研究 肺癌的病史，并将确定不同的模式 等位基因丢失发生在家族性肿瘤中(目标3)。项目的这一部分 将与项目#3、早期分子标记紧密结合 肺癌检测与3p隐性核型鉴定工程1 肺癌中的癌基因。此外，该项目可以密切互动 与开发项目1一起确定潜在的模式 肺癌易感人群对尼古丁依赖的遗传易感性 家人。 除了解决具体目标外，最重要的是 此提案的翻译应用将被标识为 一群没有症状的人，因为一种基因 易感性，可能是肺癌未来发展的候选因素 化学预防试验，项目4的目标，或开发 早期发现战略，项目3的一个目标。

It is becoming increasingly evident that the etiology of lung cancer involves a combination of both environmental and hereditary factors and that individuals may vary substantially in their genetic susceptibility to carcinogens such as tobacco. The primary goal of this project is to identify individuals genetically predisposed to be at very high risk. To do so we will establish a population-based lung cancer registry consisting of approximately 2 million. We will collect demographic, family history, and smoking data on lung cancer patients and family members. Blood samples will be collected and stored in conjunction with the SPORE Pathology Resource Core (Core B). We will perform segregation analysis on these families to fit genetic and environmental hypotheses and determine the best model characterizing familial aggregation of lung cancer (Aim 1). In doing so, we will also identify specific kindreds which will be useful for subsequent genetic linkage and candidate gene studies. Proband clinical characteristics which may be associated with increased cancer risk to family members will be determined. Sensitivity of peripheral blood lymphocyte DNA to mutagen-induced chromatid breaks will be assessed in lung cancer patients with an without a family history of lung cancer (Aim 2). In addition, we will compare patterns of allele loss in lung cancers from lung cancer patients with a family history of lung cancer and will determine if different patterns of allele loss occur in familial tumors (Aim 3). This part of the project will be closely integrated with Project #3, Molecular Markers for Early Lung Cancer Detection and Project 1, Identification of 3p Recessive Oncogenes in Lung Cancer. Moreover, this project could interact closely with Developmental Project 1 in determining patterns of potential inherited predisposition to nicotine dependency within lung cancer prone families. In addition to addressing the Specific Aims, one of the most important translational applications of this proposal will be the identification of a cohort of asymptomatic individuals who, because of a genetic predisposition, may be candidates for future development of lung cancer chemoprevention trials, a goal of Project #4, or the development of early detection strategies, a goal of Project #3.