GENETIC SUSCEPTIBILITY TO LUNG CANCER

肺癌的遗传易感性

• 批准号: 2654288
• 负责人: David C Christiani
• 金额: $ 57.3万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-10 至 2002-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2654288
• 关键词: cancer risk; clinical research; cytochrome P450; disease /disorder etiology; genetic markers; genetic polymorphism; glutathione transferase; human genetic material tag; human subject; lung neoplasms; neoplasm /cancer epidemiology; neoplasm /cancer genetics; nutrition related neoplasm /cancer; nutrition related tag; occupational disease /disorder

DESCRIPTION: (Adapted from Applicant's Abstract). The leading risk factor for lung cancer in the U.S. is cigarette smoking. The incidence of lung cancer remains alarmingly high and, despite the use of modern diagnostic and treatment modalities, the overall cure rate is low. Thus, preventive efforts, based upon the understanding of risk factors may be of paramount importance in controlling this deadly disease. A minority of smokers develops lung cancer, suggesting variability in disease susceptibility. Smoking itself may contribute to a causal complex along with other contributing factors such as genetic predisposition. Moreover, only a small proportion of all cancers is explained by simple monogenic inheritance. Several polymorphisms in the genes responsible for either activation or deactivation of carcinogens have been reported to be associated with lung cancer risk. To date, however, no studies have had sufficient statistical power to examine a number of complex gene-environment interactions in lung cancer (e.g., dietary and occupational contributions or gene-gene interactions). A large molecular epidemiologic study is proposed to examine six polymorphic traits in metabolism and lung cancer risk and how this risk may be modified by dietary or occupational exposures. The application posits that the combination of traits which enhance activation of carcinogenic metabolites and decrease detoxification of reactive products will confer excess risk in current and former smokers. Furthermore, it suggests that this risk will be modified by diet and occupational exposures. It is intended that a better understanding of these risks and their modification could lead to more effective preventive strategies.

描述：（改编自申请人摘要）。 主要风险因素 在美国，吸烟是导致肺癌的主要原因。 肺的发病率 癌症仍然高得惊人，尽管使用现代诊断和 治疗方式，总体治愈率低。 因此，预防 基于对风险因素的理解， 控制这种致命疾病的重要性。 少数吸烟者 发展成肺癌，表明疾病易感性的变异性。 吸烟本身可能与其他因素一起构成一种因果复合体沿着 影响因素，如遗传易感性。 此外，只有一个小 所有癌症的比例是由简单的单基因遗传。 负责激活或激活的基因中的几种多态性 据报道，致癌物的失活与肺 癌症风险。 然而，到目前为止，还没有任何研究有足够的统计数据。 检查肺中许多复杂的基因-环境相互作用的能力 癌症（例如，饮食和职业贡献或基因-基因 互动）。 一个大的分子流行病学研究，建议检查六个多态性 代谢和肺癌风险的特征以及如何改变这种风险 通过饮食或职业暴露。 该申请假定， 增强致癌代谢物活化的性状组合 和减少反应产物的解毒将赋予过度的风险， 现在和以前的吸烟者。 此外，它表明，这种风险将是 通过饮食和职业暴露而改变。 目的是为了更好地 了解这些风险及其修改可能会导致更多 有效的预防策略。