Molecular Epidemiology of non-Hodgkin Lymphoma Survival

非霍奇金淋巴瘤生存的分子流行病学

基本信息

批准号：
7649698
负责人：
JAMES R CERHAN
金额：
$ 60.91万
依托单位：
MAYO CLINIC ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-17 至 2011-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7649698
关键词：
Apoptotic Area Under Curve Arts B cell differentiation BCL2 gene BCL6 gene Biological Assay Cell Adhesion Molecules Cell Cycle Characteristics Classification Clinic Clinical Clinical Treatment Cohort Studies Cyclin D1 DNA Repair Gene DNA Repair Pathway Data Demographic Factors Diagnosis Differentiation Antigens Disease Progression Disease-Free Survival Enrollment Event Fluorescent in Situ Hybridization Follicular Lymphoma Functional disorder Gene Expression Genes Genetic Genetic Markers Genetic Polymorphism Genetic Variation Genotype Goals Immune Immunohistochemistry Inherited Institution Intercellular adhesion molecule 1 Iowa LMO2 gene Lead Life Style Lymphoma MME gene Malignant Neoplasms Measures Modality Modeling Molecular Molecular Epidemiology Newly Diagnosed Non-Hodgkin&apos s Lymphoma Obesity Outcome Paraffin Pathology Pathway interactions Patients Play Population Prognostic Factor Proteins Publishing Reproduction spores Resources Role Sample Size Smoking Survival Rate TP53 gene Techniques Tissue Microarray Treatment Factor Treatment Protocols Tumor Markers Tumor Tissue Universities Variant Vital Status Work angiogenesis base cancer immunotherapy candidate marker follow-up host neoplasm interaction improved large cell Diffuse non-Hodgkin&apos s lymphoma lifestyle factors molecular marker neoplastic cell novel novel strategies outcome forecast patient population prognostic prospective response rituximab tumor

项目摘要

In 2008, over 66,000 people in the US will be diagnosed with Non-Hodgkin lymphoma (NHL), and over 19,000 will die of this cancer. Survival rates have only recently begun to improve, and the current 5-year survival rate is 66%. We have identified a number of candidate host (inherited) immune genes and DNA repair genes that individually and in aggregate predict survival for follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) beyond classic clinical and demographic prognostic factors. We have also found that pre-diagnosis smoking and obesity are associated with poorer overall NHL survival. We propose to replicate and extend these provocative findings. Furthermore, building off these findings, we will evaluate whether the association of host genetics is independent of tumor molecular markers, as well as begin to explore whether there are host–tumor interactions that impact disease progression and survival. The overall goal of this study is to identify host genetic and tumor molecular markers that predict event-free and overall survival in order to improve prognostication, better understand NHL pathophysiology, and ultimately help identify approaches to improve the survival of NHL patients. Our specific aims are: 1) To evaluate the association of polymorphisms in immune and DNA repair genes with event-free and overall survival from FL and DLBCL; 2) To evaluate the association of tumor molecular markers with event-free and overall survival from FL and DLBCL; and 3) To develop multivariate prediction models for FL and DLBCL that integrate standard demographic and clinical characteristics, treatment, host genetic variation (Aim 1) and tumor molecular markers (Aim 2) to predict eventfree and overall survival. In a secondary aim, we will evaluate the role of pre-diagnosis lifestyle factors with event-free and overall survival from NHL. To achieve these aims, we will use the Lymphoma Molecular Epidemiology Resource, an ongoing, prospective prognostic cohort study of newly diagnosed cases from the Mayo Clinic and the University of Iowa initiated in 2002. This resource has several methodologic strengths, including large sample size (>2200cases), central pathology review and classification, availability of tumor tissue, detailed baseline clinical prognostic data, initial and subsequent treatments, and a large patient population treated in the immunochemotherapy (rituximab) era. We have systematically collected detailed outcome data, which will allow us to evaluate both event-free and overall survival. We will also be able to evaluate host genetic and tumor molecular prognostic factors in the context of established demographic and clinical prognostic factors, as well as all treatment(s). Upon completion of these aims, we will have simultaneously evaluated the role of host genetic variation and molecular tumor markers in the prognosis of FL and DLBCL. If host genetic factors are confirmed as robust predictors of outcome, this could lead to a fundamental shift in how patient prognosis is evaluated by incorporating host genotype into prognostic models. Host genetics may also lead to a better understanding of NHL pathophysiology that could lead to new approaches to improve the survival of NHL patients.

2008年，美国有超过66,000人被诊断出患有非霍奇金淋巴瘤（NHL），而超过19,000人将死于这种癌症。生存率直到最近才开始改善，目前的5年生存率为66％。我们已经确定了许多候选宿主（遗传的）免疫原和DNA修复基因，这些基因在经典临床和人口统计学原型因素之外单独和总体预测卵泡淋巴瘤（FL）和弥漫性大B细胞淋巴瘤（DLBCL）的生存。我们还发现，诊断前吸烟和肥胖与NHL总体存活率较差有关。我们建议复制并扩展这些挑衅性发现。此外，在建立这些发现之外，我们将评估宿主遗传学的关联是否与肿瘤分子标记无关，并开始探索是否存在影响疾病进展和生存的宿主 - 肿瘤相互作用。这项研究的总体目标是确定宿主遗传和肿瘤分子标记物，这些标志物可以预测无事件和总体存活，以改善提示，更好地了解NHL病理生理学，并最终帮助确定改善NHL患者存活的方法。我们的具体目的是：1）评估免疫和DNA修复基因中多态性的缔合与FL和DLBCL的无事件和总生存期； 2）评估肿瘤分子标记物与FL和DLBCL的无事和总生存期的关联； 3）为FL和DLBCL开发多元预测模型，以整合标准人口统计学和临床特征，治疗，宿主遗传变异（AIM 1）和肿瘤分子标记（AIM 2），以预测无事件事件和总生存期。在次要目标中，我们将通过无事件和NHL的总生存率评估诊断前生活方式因素的作用。为了实现这些目的，我们将使用淋巴瘤分子流行病学资源，这是一项持续的，前瞻性的预后群体研究，对梅奥诊所的新诊断病例和爱荷华大学的新诊断病例于2002年启动。该资源具有多种方法学的优势，包括大型样本大小（> 2200库），包括较大的临床和分类，细节，细节，细节，细节，细节，细节，细节，细节，细节，细节，细节，细节，细节，细节，细节，细节，细节，细节，细节。治疗和在免疫化学疗法（利妥昔单抗）时代接受治疗的大量患者人群。我们已经系统地收集了详细的结果数据，这将使我们能够评估无事件和整体生存。在既定的人口统计学和临床预后因素以及所有治疗方法的背景下，我们还将能够评估宿主遗传和肿瘤分子预后因素。这些目标完成后，我们将简单地评估宿主遗传变异和分子肿瘤标记在FL和DLBCL预后中的作用。如果将宿主遗传因素确认为结果的强大预测指标，则可以通过将宿主基因型纳入预后模型来评估患者提示的方式基本转移。宿主遗传学还可能导致对NHL病理生理学的更好理解，这可能导致改善NHL患者存活的新方法。