EPSTEIN-BARR VIRUS IN HODGKIN'S DISEASE

这项小额赠款项目将扩大一项正在进行的、由国家癌症研究所资助的流行病学研究， 旧金山湾区何杰金氏病病例对照研究 通过收集和整合关于EB病毒（EBV）的数据， 病例受试者的肿瘤细胞。EB病毒最近被牵连作为一个 在大约一半的HD肿瘤中，因此，HD可能是 可细分为EBV阳性和EBV阴性，将EBV数据添加到 正在进行研究将加强对生殖健康的初步调查， 通过提供更精确的疾病终点，即，HD 按EBV状态定义的亚组。小额赠款项目的目标是： 1)收集正在进行的病例受试者的存档肿瘤标本， 研究，应用标准分子病毒学技术鉴定EBV HD肿瘤细胞中的潜在基因产物，并将每个病例受试者分类为 EBV阳性或EBV阴性; 2）确定是否存在生殖风险，例如， 生育的保护作用，对于EBV阳性和EBV阴性的妇女不同， 阴性HD; 3）描述EBV阳性和EBV- 按年龄、种族和组织学亚型列出的阴性HD，并探索 与各种其他因素相关的两个病毒定义的亚组 正在测量，包括增加HD的社会阶层特征 风险这项正在进行的研究最终将涉及315名女性HD患者和315名女性HD患者。 在面对面访谈中的人口控制， 生殖、生殖使用、社会阶层、家庭、医疗和其他 生活方式的话题HD的诊断和组织学分型仍在研究中， 审查准确性。到目前为止，96%的受邀请案例主题已被 受访 对于小额赠款项目，我们将要求受访者的肿瘤 病理学家的组织标本;在一项试点研究中，我们获得了 约85%的受试者的样本。获取肿瘤样本需要时间- 有限，因为它是基于受试者签署的同意释放 正在进行的研究的病理材料，很快就会完成。 标本将邮寄给我们的合作研究者，他将测试切片， 聚合酶链反应原位检测EB病毒潜伏基因产物 杂交和免疫过氧化物酶技术来检测LMP-1， 阳性和阴性对照。该杂交方法灵敏度高， 一致，快速，不产生细胞或其他疱疹病毒交叉- 杂交方法数据分析将表征EBV阳性和EBV阴性。 目前正在调查的变量的负HD，使用描述性 统计多元统计方法将估计和比较 EBV阳性和EBV阴性HD与以下疾病相关的比值比： 生殖和其他风险因素，调整后的怀疑 混杂因素。 作为最早将联合收割机分子病毒学 和广泛的个人风险因素数据，在一个以人口为基础的系列HD 例，这个小额赠款项目将提供初步的流行病学 通过多种方法评价EBV阳性和EBV阴性HD， 假设和确定的特征会增加这种风险 淋巴瘤

This Small Grant project will expand an ongoing, NCI-funded, epidemiologic case-control study of Hodgkin's disease (HD) in San Francisco-Bay Area women by collecting and incorporating data on Epstein-Barr virus (EBV) in tumor cells of case subjects. EBV recently has been implicated as a pathogenetic cofactor in about one-half of HD tumors. As HD thus may be subclassifiable as EBV-positive and EBV-negative, addition of EBV data to the ongoing study will enhance its primary investigation of reproductive risk factors by providing more precise disease endpoints, i.e., HD subgroups defined by EBV status. The aims of this Small Grant project are: 1) to collect archived tumor specimens from case subjects in the ongoing study, apply standard molecular virologic techniques to identify EBV latent gene products in HD tumor cells, and classify each case subject as EBV-positive or EBV-negative; 2) to determine if reproductive risks, e.g., a protective effect of parity, differ for women with EBV-positive and EBV- negative HD; 3) to describe the distribution of EBV-positive and EBV- negative HD by age, race, and histologic subtype, and explore risks for the two virus-defined subgroups associated with various additional factors being measured, including social class characteristics that increase HD risk. The ongoing study ultimately will involve 315 women with HD and 315 population controls in in-person interviews covering demographic, reproductive, hormone-use, social class, familial, medical, and other lifestyle topics. Diagnosis and histologic classification of HD are being reviewed for accuracy. To date, 96% of invited case subjects have been interviewed. For the Small Grant project, we will request interviewed subjects' tumor tissue specimens from pathologists; in a pilot study, we have acquired specimens for about 85% of subjects. Access to tumor specimens is time- limited, as it is based on signed consent from subjects to release pathologic materials for the ongoing study, soon to be completed. Specimens will be mailed to our coinvestigator, who will test sections for EBV latent gene products using polymerase chain reaction, EBER in situ hybridization, and immunoperoxidase techniques to detect LMP-1, with positive and negative controls. This hybridization method is sensitive, consistent, rapid, and produces no cellular or other herpesvirus cross- hybridization. Data analysis will characterize EBV-positive and EBV- negative HD by variables presently under investigation, using descriptive statistics. Multivariate statistical methods will estimate and compare odds ratios for EBV-positive and EBV-negative HD associated with reproductive and other risk factors, after adjustment for suspected confounders. As one of the first studies to combine molecular virologic and extensive personal risk factor data in a population-based series of HD cases, this Small Grant project will provide initial epidemiologic evaluation of EBV-positive and EBV-negative HD by a variety of characteristics postulated and established to increase risk of this lymphoma.