SUSCEPTIBILITY TO MOLECULAR ALTERATION--EPITHELIAL CELLS

对分子改变的敏感性——上皮细胞

• 批准号: 6031932
• 负责人: Charles A. Powell
• 金额: $ 11.81万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-26 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6031932
• 关键词: adduct; biomarker; cancer risk; carcinogenesis; carcinogens; carotenoids; clinical research; diet; disease /disorder etiology; epithelium; female; gender difference; gene environment interaction; genetic markers; genetic polymorphism; genetic susceptibility; human subject; loss of heterozygosity; lung neoplasms; nutrition related tag; p53 gene /protein; tobacco abuse; vitamins; women's health

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.

该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有患肺癌风险的患者的生存率。这些目标将通过一个全面的计划来实现，包括正规教育，以患者为导向的研究和临床活动。 该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。以患者为导向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，妇女比类似烟草暴露的男子更容易患肺癌。 该研究项目的目标是确定DNA暴露于致癌物的生物标志物（DNA加合物）和上皮细胞中的效应生物标志物（杂合性丢失和p53突变）是否与女性肺癌易感性有关。 该项目的具体目标是确定女性上皮细胞DNA加合物、洛缺失和p53突变的程度是否与男性相似的烟草暴露不同，并确定性别、遗传多态性和饮食对这些暴露生物标志物和效应生物标志物之间关系的影响。 本研究将评估60名女性和60名男性中年吸烟者。 将在所有个体的肺、膀胱和口咽上皮细胞中评价生物标志物。 CYP1A1和GSTM 1的多态性以及维生素和类胡萝卜素的饮食摄入将被表征。 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识别个体发展为肺癌的风险增加。