Risk Factors for Molecularly Defined Subgroups of Lymphoma: A Pooled Analysis

描述(申请人提供)：染色体易位t(14；18)(q32；q21)是非霍奇金淋巴瘤最常见的染色体异常之一。虽然t(14；18)具有重要的临床意义，但其病因学意义仍有待确定。最近的两项基于人群的病例对照研究(一项在爱荷华州/明尼苏达州，另一项在内布拉斯加州)通过评估非霍奇金淋巴瘤t(14；18)阳性和t(14；18)阴性亚组的潜在危险因素来解决这一问题。这两项研究的结果表明，t(14；18)阳性的NHL与t(14；18)阴性的NHL的病因不同。然而，爱荷华州/明尼苏达州和内布拉斯加州研究的样本量限制了效果评估措施的精确度和细节。因此，我们建议使用相似的研究设计和数据收集工具对这两项研究的现有数据进行合并分析。中心创新假设是，由t(14；18)状态定义的NHL离散子集的风险因素不同。具体目的是调查t(14；18)定义的非霍奇金淋巴瘤亚型与杀虫剂、血液癌家族史和溶剂的关系是否不同。共有327例具有t(14；18)状态数据和2677例以人群为基础的对照数据将可用于汇集分析。在爱荷华州/明尼苏达州和内布拉斯加州的研究中，t(14；18)都是通过荧光原位杂交(FISH)技术确定的。NHL的亚型将由t(14；18)的存在或不存在来定义。Logistic和多分类回归模型将被用来估计暴露和t(14；18)定义的NHL亚型之间的关联，并比较t(14；18)阳性NHL和t(14；18)阴性NHL的优势比。分级回归将用于估计与特定农药暴露相关的t(14；18)阳性或t(14；18)阴性非霍奇金淋巴瘤的风险。这一结果将具有重大意义，因为它们将为疾病病因学提供新的见解。长期目标是提高我们对非霍奇金淋巴瘤发病机制的理解，以便我们最终确定可以修改的危险因素，以减少普通人群中非霍奇金淋巴瘤的发病率。由于研究人群的特征很好，而且已经收集了关于t(14；18)、杀虫剂和其他暴露的数据，因此拟议的研究对于解决NHL的病因是非常划算的，NHL是美国最常见的恶性肿瘤之一。非霍奇金淋巴瘤(NHL)是美国第五大最常见的癌症，但其病因在很大程度上尚不清楚。反复出现的染色体异常是非霍奇金淋巴瘤的标志。在众多的染色体异常中，t(14；18)是最常见的。最近在爱荷华州/明尼苏达州和内布拉斯加州进行的两项流行病学研究的结果表明，t(14；18)阳性NHL的病因不同于t(14；18)阴性的NHL。然而，个别研究的样本量还不够大，无法进行广泛的统计分析。为了解决这个问题，我们建议对这两项研究的数据进行汇集分析，得出总共327个病例的t(14；18)状态数据和2677个基于人口的对照数据。大样本量使我们能够评估暴露与t(14；18)定义的非霍奇金淋巴瘤亚组风险之间的相关性的强度和一致性。我们的长期目标是提高我们对非霍奇金淋巴瘤发展的了解，以便我们最终可以确定可以修改的危险因素，以减少普通人群中非霍奇金淋巴瘤的发生。该项目直接响应NCI癌症预防战略计划，因为它可以阐明非霍奇金淋巴瘤的病因。

DESCRIPTION (provided by applicant): The chromosomal translocation t(14;18)(q32;q21) is one of the most common chromosomal abnormalities in non-Hodgkin lymphoma (NHL). Although the t(14;18) has important clinical ramifications, its etiologic significance remains to be determined. Two recent population-based case-control studies (one in Iowa/Minnesota and the other in Nebraska) addressed this issue by evaluating potential risk factors for t(14;18)-positive and t(14;18)-negative subgroups of NHL. Findings from these two studies indicate that the causes of t(14;18)-positive NHL differ from those of t(14;18)-negative NHL. However, sample sizes of the Iowa/Minnesota and Nebraska studies limited the precision and detail of effect estimate measures. Therefore, we propose a pooled analysis of existing data from these two studies with similar study design and data collection instruments. The central innovative hypothesis is that risk factors differ for discrete subsets of NHL defined by t(14;18) status. The specific aims are to investigate whether the associations with pesticides, family history of hematopoietic cancer, and solvents differ for t(14;18)-defined subgroups of NHL. A total of 327 cases with data on t(14;18) status and 2,677 population-based controls will be available for the pooled analysis. The t(14;18) was determined by the fluorescence in-situ hybridization (FISH) technique in both the Iowa/Minnesota and Nebraska studies. Subtypes of NHL will be defined by the presence or absence of the t(14;18). Logistic and polytomous regression models will be used to estimate the associations between exposures and risk of t(14;18)-defined subtypes of NHL and to compare odds ratios for t(14;18)-positive NHL with odds ratios for t(14;18)-negative NHL. Hierarchical regression will be used to estimate the risk of t(14;18)-positive or t(14;18)-negative NHL associated with specific pesticide exposure. The results will be significant because they will provide new insights into disease etiology. The long-term objective is to improve our understanding of etiopathogenesis of NHL so that we may ultimately identify risk factors that can be modified to reduce the incidences of NHL in the general population. Because the study population is well-characterized and data on the t(14;18), pesticides, and other exposures have already been collected, the proposed study is extremely cost-effective for addressing the etiology of NHL, one of the most common malignancies in this country. Non-Hodgkin lymphoma (NHL) is the fifth most common cancer in the United States, but the causal factors are largely unknown. Recurring chromosomal abnormalities are a hallmark of NHL. Of the numerous chromosomal abnormalities, the t(14;18) is the most common one. Findings from two recent epidemiologic studies conducted in Iowa/Minnesota and Nebraska suggest that the causes of t(14;18)- positive NHL differ from those of t(14;18)-negative NHL. However, the sample size for the individual studies is not large enough for extensive statistical analysis. To address this issue, we propose a pooled analyses of data from these two studies, resulting a total of 327 cases with data on t(14;18) status and 2,677 population-based controls. The large sample size allows us to evaluate the strength and consistency of the associations between exposures and risk of t(14;18)-defined subgroups of NHL. The long-term objective is to improve our understanding of development of NHL so that we may ultimately identify risk factors that can be modified to reduce the occurrences of NHL in the general population. This project directly responds to the NCI strategic plan for cancer preemption because it can elucidate the etiology of NHL.