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CASE CONTROL STUDY OF ORAL AND PHARYNGEAL CANCER IN PUERTO RICO

波多黎各口腔癌和咽癌的病例对照研究

基本信息

批准号：
6161840
负责人：
D M WINN
金额：
--
依托单位：
NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

项目摘要

Historically, Puerto Rico has experienced high rates of oral and pharynx cancers. The principle purpose of this study is to identify sociodemographic, behavioral, nutritional, dental, and occupational risk factors for oral and pharynx cancers in Puerto Rico. In addition, the study will evaluate the role of human papilloma virus, carcinogen- metabolizing alleles, and biomarkers for malignancy and malignant transformation using biological specimens from cases and controls. This study has a population-based case-control design with more than 500 cases ascertained from the cancer registry in Puerto Rico. The more than 600 control subjects are identified using two sampling frames providing good coverage and representation of the general population: a geographic area frame and Medicare rosters. Case and control subjects are interviewed in their homes using a standardized questionnaire which obtains data on a wide range of risk factors. Biological specimens are being obtained from selected study subjects. Specimens include a blood sample, a buccal cell scraping, a urine sample, and pathologic slides. With collaboration of several academic and commercial laboratories and experts, NIDR and NCI have been evaluating methods for collecting buccal scrapings and laboratory methods for evaluating the presence of human papillomavirus in buccal cell scrapings. Data will be analyzed to determine differences between cases and controls in the extent and distribution of potential behavioral risk factors, the presence and levels of viruses, molecular markers for malignancy and carcinogen-metabolizing alleles. This study will provide insights into the etiology of oral and pharyngeal cancer, and the reasons for the high incidence rates of these cancers in Puerto Rico. This year, laboratory analysis were begun to assess the following: human papilloma virus, p53, suppressor gene mutations, CYP1A1 gene (aryl hydrocarbon hydroxylase activity), GSTM1 (glutathione S-transferase-M1), GSTT1 (glutathione S-transferase theta 1), NAT1 (arylamine N- acetyltransferase-1), NAT2, NAT1 (arylamine N-acetyltransferase-2), AhR (aryl hydrocarbon receptor). Analyses estimating the risk associated with tobacco, alcohol, diet, oral and medical characteristics are nearing completion. Alcohol dehydrogenase type 3 genotype was determined in a subset of cases and controls. Analysis of the genotype and behavioral data jointly established that a higher rate of increase in the risk of oral and pharyngeal cancer per additional alcoholic drink per week was found among persons with the ADH type 3 genotype. This finding implicates ethanol's metabolite, acetaldehyde, in the etiology of oral and pharyngeal cancer. It suggests that both behavioral and genotypic characteristics need to be addressed in prevention efforts.

从历史上看，波多黎各的口腔和咽部感染率很高癌症。本研究的主要目的是确定社会人口、行为、营养、牙科和职业风险波多黎各口腔癌和咽癌的因素。此外，研究将评估人乳头瘤病毒、致癌物质的作用代谢等位基因以及恶性肿瘤和恶性肿瘤的生物标志物使用来自病例和对照的生物标本进行转化。这研究采用基于人群的病例对照设计，涉及 500 多个病例从波多黎各的癌症登记处确定。超过600个使用两个抽样框架来识别控制对象，提供良好的一般人口的覆盖范围和代表性：地理区域框架和医疗保险名册。病例和对照对象接受采访使用标准化问卷调查他们的家，该问卷获取有关广泛的风险因素。生物标本取自选定的研究科目。样本包括血液样本、口腔细胞刮片、尿液样本和病理切片。与合作多个学术和商业实验室和专家、NIDR 和 NCI 一直在评估收集颊刮屑的方法评估人乳头瘤病毒存在的实验室方法口腔细胞刮屑。将分析数据以确定差异病例和对照之间潜在的程度和分布行为风险因素、病毒的存在和水平、分子恶性肿瘤和致癌物代谢等位基因的标记。这项研究将提供对口腔癌和咽癌病因学的见解，以及波多黎各这些癌症发病率高的原因。今年，实验室分析开始评估以下内容：人类乳头状瘤病毒，p53，抑制基因突变，CYP1A1基因（芳基烃羟化酶活性）、GSTM1（谷胱甘肽 S-转移酶-M1）、 GSTT1（谷胱甘肽 S-转移酶 theta 1）、NAT1（芳胺 N- 乙酰转移酶-1)、NAT2、NAT1（芳胺 N-乙酰转移酶-2）、AhR （芳烃受体）。分析估计相关风险烟、酒、饮食、口腔和医学特征接近完成。乙醇脱氢酶 3 型基因型测定案例和对照的子集。基因型和行为分析数据共同表明，风险增加率更高每周每多喝一杯酒精饮料，患口腔癌和咽癌的几率为发现于具有 ADH 3 型基因型的人中。这一发现暗示乙醇的代谢物乙醛在口腔和咽部病因学中的作用癌症。这表明行为和基因型特征需要在预防工作中加以解决。