Lymphoma Defined Cytogenetically for Epidemiologic Study

描述（由申请人提供）：非霍奇金淋巴瘤（NHL）的分析流行病学研究重点关注NHL亚型的风险因素是很重要的，因为：1）NHL包括一组病因各异的异质性恶性肿瘤; 2）NHL发病率的变化模式在不同亚型之间存在差异。在这个时候，NHL不能细分为流行病学研究的标准病理分类。我们建议根据BCL 2，BCL 6和C-MYC基因的重排来定义NHL，因为细胞遗传学研究表明，导致这些基因失调的反复出现的染色体异常在某些NHL亚型的发病机制中很重要。核心创新假设是，风险因素不同的离散子集NHL定义的遗传异常，其理由是，特定的，非随机的染色体异常的情况下，可能更密切相关的病因比NHL病例作为一个整体。具体目的是调查吸烟、农业和农药暴露、造血系统癌症家族史和动物脂肪饮食摄入与BCL 2再增殖阳性NHL、BCL 6再增殖阳性NHL和C-MYC再增殖阳性NHL的关联是否不同。我们估计，在内布拉斯加州进行的两项现有的基于人群的病例对照研究中，将有540个肿瘤块（其中530个将产生染色体信息）来自NHL病例，并且将有1967个对照的数据进行比较。荧光原位杂交（FISH）技术将用于确定BCL 2、BCL 6和C-MYC基因的重排。NHL的亚型将通过存在或不存在特定遗传异常来定义。将使用逻辑回归模型计算与暴露相关的NHL重排定义子集的比值比。多分类逻辑回归将用于比较通过重排定义的NHL离散子集之间的关联。这些结果将是有意义的，因为它们可以提供关于淋巴瘤发生的病因学的新见解。由于研究人群特征良好，并收集了大量的暴露数据，因此目前的建议对于解决NHL（美国最常见的恶性肿瘤之一）的病因学具有极高的成本效益。长期目标是提高对疾病过程的认识，最终可能导致在一般人群中采取适当的预防措施。

DESCRIPTION (provided by applicant): It is important that analytic epidemiologic studies of non-Hodgkin's lymphoma (NHL) focus on risk factors according to NHL subtypes because: 1) NHL comprises a heterogeneous group of malignancies that vary in etiology; and 2) the patterns of change in NHL incidence vary across different subtypes. At this time, NHL cannot be subdivided into standard pathologic categories for epidemiologic studies. We propose to define NHL according to rearrangements of the BCL2, BCL6, and C-MYC genes because cytogenetic studies have shown that recurring chromosomal abnormalities leading to the deregulation of these genes are important in the pathogenesis of certain NHL subtypes. The central innovative hypothesis is that risk factors differ for discrete subsets of NHL defined by genetic abnormalities, The rationale is that cases with specific, nonrandom chromosomal abnormalities may be more closely related etiologically than NHL cases as a whole. The specific aims are to investigate whether the associations with cigarette smoking, farming and pesticide exposure, family history of hematopoietic cancer, and dietary intake of animal fat differs for BCL2 rearrangement-positive NHL, BCL6 rearrangement-positive NHL and C-MYC rearrangement-positive NHL. We estimate that 540 tumor blocks will be available (and of which, 530 will yield chromosomal information) from NHL cases in two existing population-based, case-control studies conducted in Nebraska, and there will be data on 1967 controls for comparison. Fluorescence in-situ hybridization (FISH) technique will be used to determine the rearrangements of the BCL2, BCL6, and C-MYC genes. Subtypes of NHL will be defined by the presence or absence of the specific genetic abnormalities. Logistic regression model will be used to calculate the odds ratios for rearrangement defined subsets of NHL associated with exposures. Polytomous logistic regression will be used to compare associations across discrete subsets of NHL defined by rearrangements. The results will be significant because they could provide new insights about the etiology of lymphomagenesis. Because the study population is well-characterized and extensive data on exposures have been collected, the current proposal is extremely cost-effective to address the etiology of NHL, one of the most common malignancies in this country. The long-term objective is to improve understanding of the disease process which may ultimately lead to appropriate preventive measures in the general population.