Exposure to Organochlorines, EBV, and the Risk of NHL

描述（由申请人提供）：在过去的一个世纪里，世界范围内非霍奇金淋巴瘤（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（如农药滴滴涕和工业化学品多氯联苯）以及爱泼斯坦-巴尔病毒（EBV）在该病的病因学中起作用。与高血液/脂肪水平的有机氯相关的风险从2到4倍不等。已经确定EBV在许多免疫抑制患者的NHL病例中起因果作用，并且少数评估EBV在明显正常人群中的研究也表明EBV抗体模式的改变与NHL有关。最后，有报道称EBV和有机氯对NHL的风险有很强的统计学意义的倍增性相互作用，与低PCB/低EBV抗体组相比，高PCB/升高EBV抗体组的比值比高达22。之前的所有研究都是小规模的，需要在其他人群中进行复制。我们建议利用两组特征良好的存档血液样本——护士健康研究（一项针对女性的研究）和医生健康研究（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例事件病例，我们将把每个病例与两个具有相同疾病发展机会的对照进行匹配。我们将使用标准程序收集病理标本并对每个病例进行亚型分型，使我们能够评估这些关联是否针对特定类型的NHL。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影响因素，包括但不限于性别和饮食。该提案由一个经验丰富的研究团队领导，他们在本研究的一系列学科领域拥有专业知识。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.