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

描述（由申请人提供）：染色体易位t(14;18)（q32;q21）是非霍奇金淋巴瘤（NHL）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t（14;18）阳性和t（14;18）阴性NHL亚组的潜在危险因素来解决这个问题。这两项研究的结果表明，t（14;18）阳性NHL的病因与t（14;18）阴性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估计措施的准确性和细节。因此，我们建议采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汇总分析。核心创新假设是由t（14;18）状态定义的NHL离散亚群的危险因素不同。具体目的是调查杀虫剂、造血癌家族史和溶剂是否与NHL定义的t（14;18）亚群的相关性不同。共有327例具有t（14;18）状态数据的病例和2677例基于人群的对照将可用于合并分析。在爱荷华州/明尼苏达州和内布拉斯加州的研究中，t（14;18）由荧光原位杂交（FISH）技术测定。NHL的亚型将根据t的存在与否来定义（14;18）。将使用Logistic和多分回归模型来估计暴露与t（14;18）定义的NHL亚型风险之间的关系，并比较t（14;18）阳性NHL与t（14;18）阴性NHL的比值比。分层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NHL的风险。这些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，以减少非霍奇金淋巴瘤在普通人群中的发病率。由于研究人群具有良好的特征，并且已经收集了t（14;18）、农药和其他暴露的数据，因此拟议的研究对于解决NHL（美国最常见的恶性肿瘤之一）的病因具有极高的成本效益。非霍奇金淋巴瘤（NHL）是美国第五大常见癌症，但其病因在很大程度上尚不清楚。复发性染色体异常是NHL的标志。在众多染色体异常中，t（14;18）是最常见的染色体异常。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结果表明，t（14;18）阳性NHL的病因与t（14;18）阴性NHL的病因不同。然而，单个研究的样本量不足以进行广泛的统计分析。为了解决这一问题，我们对这两项研究的数据进行了汇总分析，得出了327例t（14;18）状态的病例和2677例基于人群的对照。大样本量使我们能够评估暴露与t（14;18）定义的NHL亚组风险之间关联的强度和一致性。长期目标是提高我们对NHL发展的理解，以便我们最终确定可以修改的风险因素，以减少NHL在普通人群中的发生。本项目可以阐明NHL的病因，直接响应NCI的癌症预防战略计划。

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.