SUSCEPTIBILITY TO MOLECULAR ALTERATION: EPITHELIAL CELLS

K23指导患者导向研究奖的目标是获得癌症遗传学、分子流行病学和患者导向研究方面的概念和技术技能，并随后应用这些技能来提高肺癌患者或肺癌发展风险患者的存活率。这些目标将通过包括正规教育、以患者为中心的研究和临床活动的综合计划来实现。教育计划将包括分子遗传学、临床流行病学和临床研究课程。定期参加与癌症和分子遗传学有关的国家会议和研讨会将是教育计划的重要组成部分。临床活动将集中在肺癌上。这项以患者为中心的研究项目的长期目标是确定导致女性肺癌发病率增加的环境和遗传因素。最近的统计趋势和病例对照研究表明，与接触类似烟草的男性相比，女性更容易患肺癌。这项研究项目的目标是确定DNA暴露于致癌物(DNA加合物)的生物标记物和上皮细胞影响的生物标记物(杂合性丧失和p53突变)是否与女性肺癌易感性有关。该项目的具体目的是确定女性上皮细胞DNA加合物、LOH和P53突变的程度是否与类似烟草暴露的男性不同，并确定性别、遗传多态和饮食对这些暴露生物标记和影响生物标记之间的关系的影响。这项研究将评估60名女性和60名男性中年吸烟者。生物标志物将在所有个体的肺、膀胱和口咽上皮细胞中进行评估。将描述CYP1A1和GSTM1的多态以及膳食中维生素和类胡萝卜素的摄入量。这些实验将提供关于遗传和环境因素如何参与女性肺癌易感性的重要信息。这些机制的定义可能允许前瞻性地识别患肺癌风险增加的个体。

The objectives for this K23 Mentored Patient Oriented Research Award are to acquire conceptual and technical skills in cancer genetics, molecular epidemiology, and patient oriented research and subsequently to apply these skills to improve the survival of patients with lung cancer or at risk for developing lung cancer. These goals will be achieved through a comprehensive program that includes formal education, patient oriented research and clinical activities. The educational program will include courses on molecular genetics, clinical epidemiology and clinical research. Regular participation in national meetings and symposia related to cancer and molecular genetics will be an essential part of the educational program. The clinical activities will be focused on lung cancer. The long-term objective for the patient oriented research project is to identify the environmental and genetic factors that are responsible for the increased incidence of lung cancer in women. Recent statistical trends and case-control studies suggest that women are more susceptible to lung cancer than men with similar tobacco exposure. The goal for this research project is to determine if biomarkers of DNA exposure to carcinogens (DNA adducts) and biomarkers of effect (loss of heterozygosity and p53 mutations) in epithelial cells are involved in lung cancer susceptibility in women. The specific aims of the project are to determine if the extent of epithelial cell DNA adducts, LOH, and p53 mutations in women is different than in men with similar tobacco exposure and to determine the effect of gender, genetic polymorphisms, and diet on the relationships among these biomarkers of exposure and biomarkers of effect. This study will evaluate 60 female and 60 male middle aged smokers. Biomarkers will be evaluated in epithelial cells from the lung, bladder and oropharynx from all individuals. Polymorphisms of CYP1A1 and GSTM1 and dietary intake of vitamins and carotenoids will be characterized. These experiments will provide important information on how genetic and environmental factors are involved in lung cancer susceptibility in women. The definition of these mechanisms may allow the prospective identification of individuals at increased risk for developing lung carcinoma.