Hodgkin Lymphoma Consortium: Pooling epidemiologic data for a research resource

描述（由申请人提供）：对于霍奇金淋巴瘤（HL），一种儿童和年轻人的常见癌症，流行病学研究已经确定了一些危险因素，但最重要的发现是患者和肿瘤特征（例如年龄、组织学亚型、肿瘤细胞Epstein-Barr病毒）之间的显著异质性。因此，HL的病因尚不清楚，这在很大程度上是因为其低发病率限制了研究样本量，特别是对于解决这种异质性所需的分层分析。因此，为了达到一级预防的最终目的，需要对HL危险因素进行更多的研究，但必须是非常大的研究。通过结合现有HL流行病学数据资源进行协作再分析的非常有效的方法，我们建议在NCI Inter Lymph consortium中组建一个HL研究联盟，汇集这些研究的数据，并最初使用汇集的数据集来检验两个在单个研究中无法解决的新假设。本研究的目的是：1)从所有参与的HL研究中获取并总结描述性信息（数据字典、问卷调查、数据资源列表）以及用于未来分析计划的核心人口统计学和肿瘤数据；2)在Inter Lymph internet门户网站上发布汇总的研究信息和汇总的核心数据频率，为规划未来的分析提供参考；3)在汇集的数据集中，测试是否：a)紫外线暴露与HL风险呈负相关；b)有和没有HL或淋巴瘤家族史的HL病例有不同的危险因素，表明环境改变了遗传易感性。22个国际HL研究的领导者已经同意共享他们的资源（约16000例HL病例和37000例对照的访谈数据、肿瘤标本和/或DNA），遵循完善和成功的Inter Lymph政策和程序。合并后的资源将成为迄今为止最大的HL病因学研究数据库之一。研究的优势包括：1)建立了一个非常强大的数据库，用于评估HL病因相关亚类内和跨亚类的新风险因素和现有风险因素，从而在一定程度上了解HL的病因和结果，这在以前是不可能的；2)极其有效地利用现有资源，以相对较小的成本获得大量的信息；3)在成功的国际流行病学研究联盟中有效利用现有基础设施；4)对两个有前景的领域的汇总数据进行初步分析：紫外线照射，一种新的可改变的HL危险因素；以及环境变化对家族性HL的影响，这对高危家庭的病因学和临床管理具有重要意义。

DESCRIPTION (provided by applicant): For Hodgkin lymphoma (HL), a common cancer of children and young adults, epidemiologic research has identified some risk factors, but the most important finding has been significant heterogeneity across patient and tumor characteristics (e.g., age, histologic subtype, tumor cell Epstein-Barr virus). Thus, the etiology of HL remains unclear, and in large part this is because its low incidence limits study sample sizes, particularly for the stratified analyses required addressing this heterogeneity. For the ultimate aim of primary prevention, additional studies of HL risk factors therefore are needed, but they must be very large. With the very efficient approach of combining existing HL epidemiologic data resources for collaborative re-analyses, we propose to form a consortium of HL studies within the NCI Inter Lymph consortium, pool data from these studies, and use the pooled dataset initially to test two novel hypotheses not addressable in individual studies. The study aims are to: 1) obtain and summarize descriptive information (data dictionaries, questionnaires, lists of data resources), and core demographic and tumor data for future analysis planning, from all participating HL studies; 2) post summarized study information and pooled core data frequencies on the Inter Lymph internet portal for reference for planning future analysis; 3) in the pooled dataset, test whether: a) ultraviolet light exposure is inversely related to HL risk; and b) HL cases with and without a family history of HL or lymphoma have differing risk factors suggesting environmental modification of genetic susceptibility. Leaders of 22 international HL studies have agreed to pool their resources (interview data, tumor specimens, and/or DNA on ~16,000 HL cases and 37,000 controls), following well-established and successful Inter Lymph policies and procedures. The pooled resource will be among the largest databases for study HL etiology ever compiled. Study strengths include: 1) producing a very powerful database for evaluating novel and extant risk factors within and across etiologically relevant subcategories of HL, for a level of insight about HL causes and outcomes not heretofore possible; 2) extremely efficient use of existing resources, with a large information gain for a relatively small cost; 3) efficient use of existing infrastructure in a successful international consortium of epidemiologic studies; 4) initial analyses in the pooled data in two promising areas: ultraviolet light exposure, a novel HL risk factor that is modifiable; and environmental modification of the well-described familial HL, with implications for etiology and clinical management of high-risk families.