Exposure to Organochlorines, EBV, and the Risk of NHL

描述（由申请人提供）：在过去的世纪，非霍奇金淋巴瘤（NHL）的发病率在全球范围内的增加在很大程度上是无法解释的。目前的流行病学证据表明，有机氯化合物（如杀虫剂滴滴涕和工业化学品多氯联苯）和EB病毒（EBV）在该病的病因学中发挥了作用。与血液/脂肪中有机氯含量高有关的风险为2至4倍。众所周知，EBV在免疫抑制患者中的许多NHL病例中起因果作用，并且在明显正常人群中评估EBV的少数研究也表明改变的EBV抗体模式与NHL相关。最后，已经报道了EBV和有机氯之间对NHL风险的强统计学显著性倍增相互作用，与低PCB/低EBV抗体组相比，高PCB/EBV抗体升高组的优势比高达22。以前的所有研究都是小规模的，需要在其他人群中重复。我们建议利用两个大的存档血液样本的特征良好的集合-护士的健康研究，女性的研究，和医生的健康研究，男性的研究-前瞻性地解决有机氯和EBV的作用和他们的潜在的相互作用在NHL的发生。我们预计在合并的研究人群中有400例事件病例，我们将每个病例与两个具有相同疾病发展机会的对照组进行匹配。我们将收集病理标本，并使用标准程序对每个病例进行分型，以评估这些相关性是否与特定类型的NHL相关。两个队列的大量资源将使我们能够评估可能的混杂因素和效应调节因素，包括但不限于性别和饮食。该提案由经验丰富的研究人员团队领导，他们拥有一系列学科的专业知识，这些学科为这项研究提供了信息，我们应该共同深入了解有机氯和EBV在NHL中的作用。

DESCRIPTION (provided by applicant): The worldwide increase in the incidence of non-Hodgkin's lymphoma (NHL) over the past century is largely unexplained. Current epidemiologic evidence suggests a role in the etiology of the disease for organochlorine compounds, such as the pesticide DDT and the industrial chemicals polychlorinated biphenyls (PCBs) and for the Epstein-Barr Virus (EBV). The risks associated with high blood/adipose levels of organochlorines have ranged from two to four-fold. It is well established that EBV plays a causal role in many cases of NHL among patients who are immune suppressed, and the few studies assessing EBV in apparently normal populations have also shown that altered EBV antibody patterns are associated with NHL. Finally, strong statistically significant multiplicative interactions between EBV and organochlorines on the risk of NHL have been reported, with odds ratios as high as 22 for the high PCB/elevated EBV antibodies group compared to the low PCBs/Iow EBV antibodies group. All of the previous studies have been small and need to be replicated in other populations. We propose to utilize two large well-characterized collections of archived blood samples - the Nurses' Health Study, a study of women, and the Physician's Health Study, a study of men - to prospectively address the role of organochlorines and EBV and their potential interaction in the occurrence of NHL. We anticipate 400 incident cases in the combined study population, and we will match each case with two controls who had the same opportunity for development of disease. We will collect pathologic specimens and subtype each case using standard procedures, allowing us to evaluate whether these associations are specific to particular types of NHL. The vast resources of the two cohorts will allow us to assess possible confounders and effect modifiers, including but not limited to, gender and diet. This proposal is led by an experienced team of researchers who have expertise over a range of disciplines that inform this study, Together, we should gain substantial insight into the role of organochlorines and EBV in NHL.