Lymphoma Defined Cytogenetically for Epidemiologic Study

淋巴瘤的细胞遗传学定义用于流行病学研究

• 批准号: 7209784
• 负责人: BRIAN C-H CHIU
• 金额: $ 19.59万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7209784
• 关键词: Address; Animals; BCL-2 Protein; BCL2 gene; BCL6 gene; Case-Control Studies; Categories; Characteristics; Chills; Chromosome abnormality; Classification Scheme; Clinical; Colon Carcinoma; Consumption; Country; Cytogenetics; DNA Sequence Rearrangement; Data; Dietary intake; Disease; Drug Formulations; Epidemiologic Studies; Etiology; Family history of; Farming environment; Fatty acid glycerol esters; Fluorescence; Fluorescent in Situ Hybridization; Future; General Population; Hematologic Neoplasms; In Situ Hybridization; Incidence; Knowledge; Lead; Link; Logistic Regressions; Lymphoma; Lymphomagenesis; MYC gene; Malignant Neoplasms; Measures; Meat; Modeling; Molecular Abnormality; Nebraska; Non-Hodgkin' s Lymphoma; Odds Ratio; Oncogene Deregulation; Other Finding; Outcome; Pathogenesis; Pathologic; Pattern; Personal Satisfaction; Population; Population Study; Prevention strategy; Preventive; Process; Proto-Oncogenes; Questionnaires; Research Personnel; Research Project Grants; Risk; Risk Factors; Source; Specificity; Standards of Weights and Measures; Techniques; Time; Tissue Sample; Work; base; cigarette smoking; cost; improved; innovation; insight; leukemia; malignant breast neoplasm; outcome forecast; pesticide exposure; prognostic; programs; tumor

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.

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应重点关注 NHL 亚型的危险因素，这一点很重要，因为： 1) NHL 包含一组病因各异的异质性恶性肿瘤； 2) NHL 发病率的变化模式因不同亚型而异。目前，NHL 无法再细分为流行病学研究的标准病理类别。我们建议根据 BCL2、BCL6 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 亚型的发病机制中非常重要。核心创新假设是，由遗传异常定义的 NHL 离散子集的危险因素有所不同，其基本原理是，具有特定非随机染色体异常的病例在病因学上可能比整个 NHL 病例更密切相关。具体目的是调查 BCL2 重排阳性 NHL、BCL6 重排阳性 NHL 和 C-MYC 重排阳性与吸烟、农业和农药暴露、造血系统癌症家族史以及动物脂肪饮食摄入量之间的关联是否存在差异。国家冰球联盟。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，将从 NHL 病例中获得 540 个肿瘤块（其中 530 个将产生染色体信息），并且将有 1967 年对照的数据进行比较。荧光原位杂交 (FISH) 技术将用于确定 BCL2、BCL6 和 C-MYC 基因的重排。 NHL 的亚型将根据特定遗传异常的存在或不存在来定义。 Logistic 回归模型将用于计算与暴露相关的 NHL 重排定义子集的优势比。多分逻辑回归将用于比较由重排定义的 NHL 离散子集之间的关联。这些结果将具有重要意义，因为它们可以提供有关淋巴瘤发生病因学的新见解。由于研究人群特征明确，并且已经收集了有关暴露的大量数据，因此当前的提议对于解决 NHL（该国最常见的恶性肿瘤之一）的病因学而言极具成本效益。长期目标是提高对疾病过程的了解，最终可能为普通人群采取适当的预防措施。