Exposure to Organochlorines, EBV, and the Risk of NHL

描述(申请人提供)：在过去的一个世纪里，全球非霍奇金淋巴瘤(NHL)发病率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(PCBS)以及爱泼斯坦-巴尔病毒(EBV)在疾病病因学中发挥了作用。与血液/脂肪含量较高的有机氯相关的风险从两倍到四倍不等。众所周知，在免疫抑制的患者中，EBV在许多NHL病例中起着因果作用，少数在明显正常人群中评估EBV的研究也表明，EBV抗体模式的改变与NHL有关。最后，已经报道了EBV和有机氯之间在非霍奇金淋巴瘤风险方面具有很强的统计学意义的乘性相互作用，与低PCBS/低EBV抗体组相比，高PCB/高EBV抗体组的优势比高达22。之前的所有研究都是小规模的，需要在其他人群中复制。我们建议利用两个大型的、具有良好特征的存档血液样本收集--护士健康研究，一项针对女性的研究，以及医生健康研究，一项针对男性的研究--前瞻性地探讨有机氯和EBV在NHL发生中的作用及其潜在的相互作用。我们预计在联合研究人群中有400个事件病例，我们将每个病例与两个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，使我们能够评估这些关联是否特定于特定类型的NHL。这两个群体的巨大资源将使我们能够评估可能的混杂因素和影响因素，包括但不限于性别和饮食。这项建议是由一个经验丰富的研究人员团队领导的，他们拥有一系列学科的专业知识，这些专业知识为这项研究提供了信息，我们应该一起对有机氯化合物和EBV在非霍奇金淋巴瘤中的作用有实质性的了解。

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.