Molecular Epidemiology and Molecular Carcinogenesis of H

H 的分子流行病学和分子致癌作用

• 批准号: 7038535
• 负责人: CURTIS HARRIS
• 金额: --
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7038535
• 关键词: cancer risk; carcinogenesis; carcinogens; chronic disease /disorder; clinical research; colon neoplasms; environment related neoplasm /cancer; environmental exposure; gene environment interaction; gene mutation; genetic susceptibility; health disparity; human genetic material tag; human population genetics; human subject; inflammation; lung neoplasms; neoplasm /cancer epidemiology; neoplasm /cancer genetics; racial /ethnic difference; tobacco abuse

Gene-environment interaction is a seminal concept in molecular epidemiology of human cancer. Our case-control (using hospital- and population-based controls) studies focus on lung cancer, a tobacco-related cancer, and colon cancer, one of the cancer types associated with chronic inflammation. These studies require the integration of an increasing understanding of genetic variation in cancer susceptibility, analysis of carcinogen exposure, rapidly developing technologies, bioinformatics, social-ethical concerns, and epidemiological study-design methods. We have discovered that a deficient G2/M cell cycle checkpoint that responded to DNA damage, a phenotypic trait, is associated with a higher lung cancer risk in African-Americans than in Caucasians. Genotypic polymorphisms of certain inflammatory cytokine genes, e.g., IL-1? and IL-10, were also associated with lung cancer. We are continuing our longstanding studies of human lung carcinogenesis. The molecular profile of adenocarcinoma identified smoking- versus nonsmoking-associated cancers and short-term versus long-term survivors. Our studies of neuroendocrine lung cancer revealed their specific molecular signatures, e.g., carboxypeptidase E was a significant predictor of good prognosis, whereas increased expression of ?-glutamyl hydrolase predicted poor prognosis. We will continue to focus on tobacco-related cancer, inflammation and cancer, and cancer-related health disparities.

基因-环境相互作用是人类肿瘤分子流行病学中的一个重要概念。我们的病例对照（使用基于医院和人群的对照）研究集中在肺癌（一种与烟草相关的癌症）和结肠癌（一种与慢性炎症相关的癌症类型）。这些研究需要整合对癌症易感性遗传变异的日益理解、致癌物暴露分析、快速发展的技术、生物信息学、社会伦理问题和流行病学研究设计方法。我们已经发现，对DNA损伤（一种表型性状）做出反应的G2/M细胞周期检查点缺陷与非洲裔美国人比白人更高的肺癌风险相关。某些炎性细胞因子基因的基因型多态性，例如，IL-1？和IL-10也与肺癌有关。我们正在继续我们长期以来对人类肺癌的研究。腺癌的分子特征确定了吸烟与不吸烟相关的癌症以及短期与长期生存者。我们对神经内分泌肺癌的研究揭示了它们的特异性分子特征，例如，羧肽酶E是良好预后的重要预测因子，而？谷氨酰水解酶预测预后不良。我们将继续关注与烟草有关的癌症、炎症和癌症以及与癌症有关的健康差距。