Molecular Epidemiology and Molecular Carcinogenesis of H

基因-环境相互作用是人类癌症分子流行病学中的一个开创性概念。我们的病例对照研究(使用基于医院和人群的对照)集中在肺癌，一种与烟草相关的癌症，以及结肠癌，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的遗传变异的日益加深的了解、致癌物暴露的分析、快速发展的技术、生物信息学、社会伦理关注和流行病学研究设计方法。我们发现，对DNA损伤做出反应的G2/M细胞周期检查点缺陷，这是一种表型特征，与非裔美国人比高加索人更高的肺癌风险有关。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，GSTT1缺失多态、Asp72Pro TP53多态或Asp302His CASP8多态与结肠癌风险呈正相关。在与Alavanja的合作下，我们扩大了我们之前对不吸烟女性肺癌的分子流行病学研究。除了GSTM1缺失多态会增加二手烟诱发肺癌的风险外，GSTM1缺失还会增加这些女性患环境氡诱发肺癌的风险。我们正在继续我们对人类肺癌发生的长期研究。腺癌的分子图谱确定了吸烟与非吸烟相关的癌症，以及短期与长期存活者。我们还发现了microRNAs的分子图谱，这是一种非蛋白编码基因，用于识别肺癌、其不同的组织类型和预后。这些发现正在扩展到其他类型的癌症，包括结肠癌和食道癌，以及人类癌症的动物模型。

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.