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

分子定义的淋巴瘤亚组的危险因素：汇总分析

• 批准号: 7921315
• 负责人: BRIAN C-H CHIU
• 金额: $ 6.33万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-27 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7921315
• 关键词: Address; BCL-2 Protein; Case-Control Studies; Characteristics; Chemicals; Chromosomal translocation; Chromosome abnormality; Class; Classification; Clinical; Country; Data; Data Analyses; Data Collection; Data Set; Development; Disease; Disease regression; Epidemiologic Studies; Etiology; Event; Family history of; First Degree Relative; Fluorescent in Situ Hybridization; General Population; Grant; Hematologic Neoplasms; Herbicides; Incidence; Individual; Insecticides; Iowa; Lead; Life Style; Logistics; Lymphoma; Malignant Neoplasms; Measures; Mediating; Minnesota; Modeling; Molecular; Multiple Myeloma; NCI Strategic Planning; Nebraska; Non-Hodgkin' s Lymphoma; Odds Ratio; Pathogenesis; Personal Satisfaction; Pesticides; Population; Population Study; Prevention strategy; Relative (related person); Reporting; Research; Research Design; Research Project Grants; Resources; Risk; Risk Estimate; Risk Factors; Sample Size; Solvents; Specificity; Subgroup; Techniques; United States; World Health Organization; base; cancer epidemiology; cancer risk; cost; improved; innovation; insight; instrument; interest; leukemia; outcome forecast; pesticide exposure; programs; t(14; 18)(q32; q21)

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.

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) 中最常见的染色体异常之一。尽管 t(14;18) 具有重要的临床影响，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 NHL t(14;18) 阳性和 t(14;18) 阴性亚组的潜在危险因素解决了这个问题。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精度和细节。因此，我们建议对这两项具有相似研究设计和数据收集工具的研究的现有数据进行汇总分析。中心创新假设是，对于由 t(14;18) 状态定义的 NHL 离散子集，风险因素有所不同。具体目的是调查 t(14;18) 定义的 NHL 亚组与农药、造血系统癌症家族史和溶剂的关联是否存在差异。总共 327 个具有 t(14;18) 状态数据的病例和 2,677 个基于人群的对照将可用于汇总分析。在爱荷华州/明尼苏达州和内布拉斯加州的研究中，t(14;18) 是通过荧光原位杂交 (FISH) 技术测定的。 NHL 的亚型将通过 t(14;18) 的存在或不存在来定义。 Logistic 和多元回归模型将用于估计 t(14;18) 定义的 NHL 亚型的暴露与风险之间的关联，并比较 t(14;18) 阳性 NHL 的优势比与 t(14) 的优势比;18)-阴性NHL。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 风险。结果将具有重要意义，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 NHL 发病机制的了解，以便我们最终确定可以修改的危险因素，以减少一般人群中 NHL 的发病率。由于研究人群特征明确，并且已经收集了有关 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（最常见的恶性肿瘤之一）的病因学而言极具成本效益在这个国家。非霍奇金淋巴瘤 (NHL) 是美国第五大常见癌症，但其病因很大程度上尚不清楚。反复出现的染色体异常是 NHL 的一个标志。在众多染色体异常中，t(14;18) 是最常见的一种。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 的原因与 t(14;18) 阴性 NHL 的原因不同。然而，个别研究的样本量不足以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总分析，得出总共 327 个具有 t(14;18) 状态数据的病例和 2,677 个基于人群的对照。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 发展的了解，以便我们最终确定可以修改的风险因素，以减少一般人群中 NHL 的发生。该项目直接响应了NCI癌症先发制人的战略计划，因为它可以阐明NHL的病因。