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: 7337863
• 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/7337863
• 关键词: Molecular; Epidemiology; Carcinogenesis

Gene-environment interaction is a seminal concept in the 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. We have developed a novel bioinformatic approach to identify SNP-SNP interactions and generate hypotheses. For example, the GSTT1-null polymorphism, the Asp72Pro TP53 polymorphism or the Asp302His CASP8 polymorphism was positively correlated with colon cancer risk. In collaboration with Alavanja, we have extended our previous molecular epidemiological studies of lung cancer in never-smoking women. In addition to the GSTM1-null polymorphism increasing the risk of secondhand smoke-induced lung cancer, GSTM1 null also increases the risk of environmental radon-induced lung cancer in these women. 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. We have also discovered molecular profiles of microRNAs, nonprotein coding genes that identify lung cancer, its different histological types and prognosis. These findings are being extended to other cancer types including colon and esophageal cancer, and to animal models of human cancer.

基因-环境相互作用是人类癌症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高加索人更高的肺癌风险相关。我们开发了一种新的生物信息学方法来识别SNP-SNP相互作用并产生假设。例如，GSTT 1-null多态性、Asp 72 Pro TP 53多态性或Asp 302 His CASP 8多态性与结肠癌风险正相关。在与Alavanja的合作中，我们扩展了我们以前对从不吸烟女性肺癌的分子流行病学研究。除了GSTM 1缺失多态性增加二手烟诱发肺癌的风险外，GSTM 1缺失也增加了这些女性环境氡诱发肺癌的风险。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。我们还发现了microRNA的分子谱，microRNA是识别肺癌、其不同组织学类型和预后的非蛋白质编码基因。这些发现正在扩展到其他癌症类型，包括结肠癌和食道癌，以及人类癌症的动物模型。