A prospective analysis of peripheral blood cytokines and non-Hodgkin lymphoma

外周血细胞因子与非霍奇金淋巴瘤的前瞻性分析

• 批准号: 8508681
• 负责人: BRENDA M BIRMANN
• 金额: $ 56.02万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8508681
• 关键词: Address; Adult; Autoimmune Diseases; Autoimmune Process; Autoimmunity; B-Lymphocytes; Basic Science; Biological Assay; Biological Markers; Blood specimen; C-reactive protein; CXCL13 gene; Cancer Etiology; Cell Lineage; Cessation of life; Chronic; Clinical Sciences; Cohort Studies; DNA; Data Analyses; Diagnosis; Diagnostic; Early Diagnosis; Elderly; Epidemiologist; Epstein-Barr Virus Infections; Etiology; Future; Health Professional; Hematologic Neoplasms; High-Risk Cancer; Histologic; Hormones; Human; Human Herpesvirus 4; IL2RA gene; IgE; Immune; Immune response; Immunocompetent; Immunologic Markers; Immunologist; Immunosuppression; Inflammation; Inflammatory; Inflammatory Response; Interleukin 2 Receptor; Interleukin-6; Knowledge; Logistic Regressions; Lymphocyte Activation; Malignant - descriptor; Malignant Neoplasms; Measures; Mediating; Minority; Modification; Molecular; Non-Hodgkin' s Lymphoma; Nurses' Health Study; Pathologic; Pathology; Patients; Pattern; Persons; Plasma; Population; Prevalence; Prevention strategy; Process; Production; Prospective Studies; Public Health; Publishing; Qualifying; Questionnaires; Reporting; Resources; Risk; Risk Factors; Role; Sampling; Specimen; T-Cell Activation; T-Lymphocyte; TNFR-Fc fusion protein; TNFRSF8 gene; Technology; Testing; Tissue Microarray; Tissues; Tumor Necrosis Factor-alpha; United States; World Health Organization; base; biobank; cancer diagnosis; cohort; cytokine; digital imaging; experience; follow-up; innovation; insight; large cell Diffuse non-Hodgkin' s lymphoma; lymphoid neoplasm; multidisciplinary; novel; peripheral blood; population based; prospective; response; tumor

DESCRIPTION (provided by applicant): Non-Hodgkin lymphoma (NHL) comprises a heterogeneous group of >30 lymphoid neoplasms, >85% of which are of B cell lineage. NHL presents a considerable public health burden with >80,500 new diagnoses and 24,600 deaths expected in 2010. The etiology of NHL is poorly understood, but it is known that overt immune compromise is a strong risk factor. Immune dysregulation may also be important in the etiology of NHL in persons with no overt immune deficiency. The Epstein-Barr virus (EBV) is detected in a sizeable minority of NHL in immune competent persons, but neither the true prevalence nor risk factors for EBV+ NHL are known. Th17, Th1, and Th2 cytokines mediate human immune responses and may be associated with NHL risk by virtue of their roles in B and T lymphocyte activation and inflammation. The Th17 response leads to the induction of several B cell stimulatory cytokines; this axis is also implicated in autoimmune disease, and persons with autoimmune conditions have an increased risk of NHL. It is plausible that Th17 dysregulation, and/or dysregulation of Th1 or Th2 or inflammatory responses, is associated with NHL risk in apparently immune competent adults. Cytokines also mediate host control of EBV and thus may also predict risk of EBV+ NHL. To examine these hypotheses, we will conduct prospective studies nested within the Nurses' Health Study and Health Professionals Follow-up Study cohorts. In a projected pooled sample of 670 cases and 1340 matched controls, we will measure a panel of immune markers in pre-diagnostic plasma samples. We will collect tissue specimens from NHL cases for pathologic studies to determine WHO-defined histologic subtype, diffuse large B-cell lymphoma (DLBCL) molecular subtype, and EBV status. We will use conditional logistic regression to assess the association of plasma immune markers indicative of altered Th17, Th1, Th2 and/or inflammatory responses with NHL. We will evaluate confounding by other NHL risk factors and conduct secondary analyses to examine effect modification and explore the correlation of plasma immune markers with those other factors. With these studies we will be the first to examine the etiologic role of the Th17 response in NHL, to report population-based prevalences of EBV+ NHL by subtype and of DLBCL subtypes, and to prospectively evaluate risk factors for EBV+ NHL. The multidisciplinary study team features epidemiologists (Drs. Birmann, Laden, and Giovannucci), a senior biostatistician (Dr. Rosner), and immunologists (Drs. Martmnez-Maza and Breen) and hematopathologists (Drs. Aster and Rodig) with substantial relevant experience-i.e, in the use of plasma immune markers in etiologic studies, prospective data analysis, and the pathologic determination of NHL histologic type and tumor EBV status. With this highly qualified team, the extraordinary resources of the cohorts, and the proposed studies, we are uniquely situated to contribute novel insights on the role of immune dysregulation in the etiology of NHL and EBV+ NHL in immunocompetent adults.

描述（由申请人提供）：非霍奇金淋巴瘤（NHL）包括一个> 30个> 30个淋巴肿瘤的异质组，其中85％是B细胞谱系。 NHL表现出可观的公共卫生负担，预计在2010年预计80,500次新诊断和24,600人死亡。NHL的病因学很少了解，但众所周知，明显的免疫妥协是强大的危险因素。免疫失调在没有明显免疫缺陷的人的NHL病因中也可能很重要。在免疫能力的人中，在相当大的NHL中检测到Epstein-Barr病毒（EBV），但EBV+ NHL的真实患病率和风险因素均未知道。 Th17，Th1和Th2细胞因子介导了人类的免疫反应，并且可能由于其在B和T淋巴细胞激活和炎症中的作用而与NHL风险有关。 TH17的反应导致诱导几种B细胞刺激细胞因子。该轴也与自身免疫性疾病有关，并且具有自身免疫性状况的人的NHL风险增加。 Th17失调和/或TH1或TH2或炎症反应失调的失调和/或失调与NHL的风险显然是免疫能力的成年人有关，这是合理的。细胞因子还介导对EBV的宿主控制，因此也可能预测EBV+ NHL的风险。为了审查这些假设，我们将进行嵌套在护士健康研究和卫生专业人员随访研究中的前瞻性研究。在预计的670例病例和1340个匹配的对照组的汇总样品中，我们将测量诊断前血浆样品中的一组免疫标记。我们将从NHL病例中收集组织样本进行病理研究，以确定谁定义的组织学亚型，扩散大的B细胞淋巴瘤（DLBCL）分子亚型和EBV状态。我们将使用条件逻辑回归来评估血浆免疫标记的关联，指示TH17，TH1，TH2和/或NHL炎症反应改变。我们将评估其他NHL风险因素的混淆，并进行次要分析，以检查效果修改并探索血浆免疫标记与其他因素的相关性。通过这些研究，我们将是第一个研究TH17反应在NHL中的病因作用，以亚型和DLBCL亚型报告基于人群的EBV+ NHL的流行率，并向前瞻性评估EBV+ NHL的风险因素。多学科研究团队由流行病学家（Birmann博士，Laden和Giovannucci博士），一位高级生物统计学家（Rosner博士）和免疫学家（Rosner）和免疫学家（Martmnez-Maza and Breen和Breen博士）和血液病理学家（Drs and Rodig and Rodig。分析以及NHL组织学类型和肿瘤EBV状态的病理确定。借助这支高素质的团队，同伙的非凡资源以及拟议的研究，我们独特地定位于对免疫失调在NHL和EBV+ NHL病因中的作用的新见解，在免疫能力的成年人中。