Case-Control Study of Pesticides and t(14;18) Lymphoma

描述（由申请人提供）： 一项基于人群的非霍奇金淋巴瘤病例对照研究， 1983年至1986年在内布拉斯加州进行。NCI的研究收集了 关于农业暴露的广泛信息。在此，辅助 分子研究建议确定农药在 t（14;18）染色体易位的发生。 NHL和杀虫剂之间的联系已经被反复观察到， 并不一致。农药和NHL的流行病学研究结果可能 被病因学上 多样化。t（14;18）是最常见的细胞遗传学异常， t（14;18）介导的BCL 2蛋白的组成性过表达是一种重要的 NHL发病机制的早期事件。目前的建议将分类NHL病例 根据t（14;18）状态，识别可能的农业风险因素， 特异性与t（14;18）阳性或阴性致病性 机制等具体目标是：1）获得石蜡包埋的肿瘤块 对于NHL病例; 2）确定t（14;18）易位的存在;和3） 研究杀虫剂与t（14;18）阳性NHL相关性， t（14;18）阴性NHL。假设杀虫剂的作用是 沿着t（14;18）依赖性途径，导致与 t（14;18）阳性者多于t（14;18）阴性者。研究设计是一个 分子病例对照研究将从淋巴瘤中获得肿瘤组织块 原始病例对照研究中所有NHL病例的登记组织库 （约270-290个组织块可用）。荧光原位 杂交（FISH）分析将用于确定是否存在 t（14;18）易位。FISH分析的结果将用于分类 NHL分为t（14;18）阳性NHL和t（14;18）阴性NHL。Logistic 回归模型将用于计算以下各项的比值比： t（14;18）阳性和t（14;18）阴性NHL与不同人群相关 杀虫剂的种类。短期目标是提高对 疾病的过程，这可能最终导致改善预防非霍奇金淋巴瘤， 普通民众。

DESCRIPTION (provided by applicant): A population-based, case-control study of non-Hodgkin's lymphoma (NHL) was conducted in Nebraska between 1983 and 1986. This NCI's study collected extensive information on agricultural exposures. Herein, an ancillary molecular study is proposed to determine the role of pesticides in the occurrence of t(14;18) chromosomal translocation in this case-control study. An association between NHL and pesticides has been observed repeatedly, but not consistently. Results of epidemiologic studies of pesticides and NHL may be obscured by the aggregate evaluation of cases that are etiologically diverse. The t(14;18) is the most common cytogenetic abnormality, and t(14;18)-mediated constitutive overexpression of BCL2 protein is an important early event in NHL pathogenesis. The current proposal will classify NHL cases according to t(14;18) status to identify agricultural risk factors that may be specifically associated with t(14;18)-positive or -negative pathogenic mechanisms. The specific aims are to 1) obtain paraffin-embedded tumor blocks for NHL cases; 2) determine the presence of the t(14;18) translocation; and 3) investigate pesticides for their association with t(14;18)-positive NHL or t(14;18)-negative NHL. The hypothesis is that pesticides act specifically along a t(14;18)-dependent pathway, resulting in stronger associations with t(14;18)-positive than t(14;18)-negative NHL. The research design is a molecular case-control study. Tumor blocks will be obtained from the Lymphoma Registry Tissue Bank for all NHL cases in the original case-control study (about 270-290 tissue blocks will be available). Fluorescence in-situ hybridization (FISH) analysis will be used to determine the presence of the t(14;18) translocation. Results from FISH analyses will be used to classify NHL cases into t(14;18)-positive NHL or t(14;18)-negative NHL. Logistic regression models will be used to calculate the odds ratios for t(14;18)-positive NHL and t(14;18)-negative NHL associated with various groups and types of pesticides. The low-term objective is to improve understanding of the disease process which may ultimately lead to improved prevention of NHL in the general population.