GENETIC SUSCEPTIBILITY TO LUNG CANCER

为了达到国家癌症研究所降低癌症死亡率的目标 到2000年时达到50%， 预防肺癌，美国癌症死亡率的主要原因 在男性和女性中。初级预防战略包括： 传统上是以人口为基础的努力，以减少吸烟。 然而，即使在长期暴露于环境中的人中， 由于长期吸烟，患肺癌的机会相对较低。 初步研究表明，这种风险分布不均匀， 家庭中的某些个体患肺癌的风险更高 发展这种家族聚集性表明， 易感性可能是致癌的一个因素。更有效的 预防策略可以设计，如果这些人可以 鉴定 以前的研究已经确定了一些基因，可能会影响 对肺癌的易感性。这些基因座被认为介导肺癌 通过解毒（或未能解毒）常见的 环境因素，如香烟烟雾。这个的主要目标 一项研究将肺癌易感性与DNA变异联系起来， 解毒基因座的两个超家族，P450和GST家族。联合 对这些基因变异的评估将允许精确的 确定每个基因座对肺癌的相对贡献 风险基因图谱将用于寻找相关的 病原学位点的变化（特征在于 应用）和家族史的差异。这些配置文件还将 用于研究遗传构成的反馈是否会影响 对风险的认识和对公共卫生建议的遵守情况， 高危人群。

To reach the National Cancer Institute's goal of reducing cancer mortality 50% by the year 2000, significant progress will have to be made in the prevention of lung cancer, the leading cause of U.S. cancer mortality among both men and women. The primary prevention strategy has traditionally been a population based effort to reduce cigarette smoking. However, even among individuals with chronic environmental exposures, such as long term cigarette smoking, the risk of lung cancer is relatively low. Preliminary studies suggest that this risk is unevenly distributed, with certain individuals in families having much greater risks of lung cancer development. Such clustering in families suggests that genetic susceptibility may be a factor in carcinogenesis. A more effective prevention strategy could be designed if these individuals could be identified. Previous studies have identified a number of genes that may influence susceptibility to lung cancer. These loci are felt to mediate lung cancer risk through the detoxification of (or failure to detoxify) common environmental agents such as cigarette smoke. The primary goal of this study is to relate lung cancer susceptibility to DNA based variation among two superfamilies of detoxification loci, the P450 and GST families. Joint evaluation of variation of these genes will permit the precise determination of the relative contribution of each locus to lung cancer risk. The genetic profiles will then be used to look for associated changes in etiologic loci (characterized in other components of the application) and differences in family history. The profiles will also be used to investigate whether feedback on genetic constitution influences perception of risk and adherence to public health recommendations among high risk individuals.