GENETIC SUSCEPTIBILITY TO LUNG CANCER

肺癌的病因学越来越明显， 涉及环境和遗传因素的结合， 个体的遗传易感性可能会有很大的差异， 致癌物质，如烟草。 该项目的主要目标是 确定在遗传上有极高风险倾向的个体。 为此，我们将建立一个以人口为基础的肺癌登记处 约有200万人。 我们将收集人口统计数据， 肺癌患者和家庭的家族史和吸烟数据 成员血液样本的采集和储存将与 SPORE病理学资源核心（核心B）。我们将执行隔离 对这些家庭进行分析，以符合遗传和环境假设 并确定表征肺的家族聚集性的最佳模型 癌症（目标1）。在此过程中，我们还将确定特定的kinematic 这将有助于后续的遗传连锁和候选基因 问题研究 可能与以下疾病相关的先证者临床特征 将确定家庭成员患癌症的风险增加。 灵敏度 外周血淋巴细胞DNA对诱变剂诱导的染色单体断裂的影响 将在没有家庭的肺癌患者中进行评估 肺癌病史（目标2）。 此外，我们将比较模式 来自有家族史的肺癌患者的肺癌等位基因丢失 肺癌的历史，并将确定是否有不同的模式， 等位基因丢失发生在家族性肿瘤中（Aim 3）。这部分项目 将与项目#3紧密结合，早期分子标记 肺癌检测和项目1，3p隐性基因的鉴定 肺癌中的癌基因 此外，该项目可以密切互动， 与发展项目1在确定模式的潜力 肺癌易感人群中尼古丁依赖的遗传易感性 家庭 除了具体目标外，最重要的目标之一是 这一建议的翻译应用将是识别 一群无症状的个体，由于遗传原因， 易感性，可能是未来肺癌发展的候选人 化学预防试验，项目#4的目标，或开发 早期检测策略，项目#3的目标。

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.