CANCER OF THE HEAD & NECK--EPIDEMIOLOGY AND BIOCHEMISTRY

人类癌症的诱发和发展过程 复杂的流行病学数据表明，许多人参与了 各种因素。肿瘤发生前数年的病毒感染 可能是几个诱发因素之一。细胞癌基因激活， 仅次于基因改变的另一个因素被认为是重要的 在人类的恶性肿瘤中。这项研究提案的具体目的是 检验病毒感染与增加的风险有关的假设 头颈部癌(S)与发现的关系 激活的癌基因和这些相同的癌症。 调查将采取病例对照研究的形式。这项研究 人口将包括来自中国医生的大约1200名患者 隆氏医院耳鼻咽喉、外科、内科和牙科 岛犹太人-希尔赛德医疗中心。病例(600例)将是 新诊断和治疗的疾病：口腔鳞状细胞癌 腔、口咽、鼻咽、下咽、喉、腺和鳞 食道细胞癌，头颈部淋巴瘤，或 恶性唾液腺肿瘤。对照(600人)将为患者 对同一部位的良性疾病进行外科治疗。 既往感染的发生将通过以下方式确定：病史、血清学 以及对存在病毒的组织进行生化分析 Southern杂交、DNA/RNA斑点杂交和原位杂交检测基因组和RNA转录本 与分子克隆的病毒DNA探针杂交，以及病毒衣壳和 冰冻切片免疫过氧化物酶抗体染色检测核抗原 和印痕涂片。如果新的人乳头瘤病毒相关序列 一旦确认，我们将尝试克隆病毒DNA分子。他的存在 激活的癌基因将通过RNA斑点印迹进行生化研究， 分子克隆癌基因的Northern杂交和原位杂交 探测器。该项目的两个部分-寻找病毒和致癌基因 参与将同时进行。 如果得到资助，这将是第一次大规模的病例控制流行病学研究 头颈部癌的生化水平及临床应用研究 提供客观证据，帮助评估病毒是否 病因学和/或已知的癌基因参与其中。从更广泛的意义上讲，这 信息将有助于我们对相互作用的理解 人类病毒、癌基因和癌症之间的关系。

The process of induction and progression of human cancer is exceedingly complex and epidemiologic data suggest the involvement of a multitude of factors. Viral infection years prior to the development of the neoplasm may be one of several precipitating factors. Cellular oncogene activation, secondary to genetic alteration, is another factor believed to be important in human malignancies. The specific aims of this research proposal are to test the hypothesis that viral infection is related to an increased risk of cancer(s) of the head and neck, and to discover the relationship between activated oncogenes and these same cancers. The investigation will take the form of a case-control study. The study population will consist of approximately 1200 patients from physicians in the Departments of Otolaryngology, Surgery, Medicine and Dentistry at Long Island Jewish-Hillside Medical Center. Cases (600) will be patients who are newly diagnosed and treated for: squamous cell carcinomas of the oral cavity, oropharynx, nasopharynx, hypopharynx, larynx, adeno and squamous cell carcinomas of the esophagus, lymphomas of the head and neck, or malignant salivary gland tumors. Controls (600) will be patients surgically treated for benign diseases of the same sites. The occurrence of past infection will be ascertained by: history, serology and biochemical analysis of tissues obtained for the presence of the viral genome and RNA transcripts by Southern blots, DNA/RNA dot blot and in situ hybridizations to molecularly cloned viral DNA probes, and viral capsid and nuclear antigens by immunoperoxidase antibody staining of frozen sections and impression smears. If novel human papillomavirus-related sequences are identified, we will attempt to clone the viral DNA molecule. The presence of activated oncogenes will be studied biochemically by RNA dot blot, Northern blot and in situ hybridizations to molecularly cloned oncogene probes. The two sections of the project - looking for viral and oncogene involvement will be done concurrently. If funded, this would be the first large-scale case-control epidemiologic study of cancers of the head and neck at the biochemical level and would provide objective evidence which should help in evaluating whether a viral etiology and/or known oncogenes are involved. In a broader sense, this information will contribute to our understanding of the interactions between human viruses and oncogenes and cancer.