Impact of Lifestyle with Tumor Pathways and Microenvironment on Lymphoma Survival

生活方式与肿瘤途径和微环境对淋巴瘤生存的影响

基本信息

批准号：
8245331
负责人：
BRIAN C-H CHIU
金额：
$ 3.22万
依托单位：
UNIV OF MASSACHUSETTS MED SCH WORCESTER
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 2011-12-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8245331
关键词：
Impact Lifestyle Tumor Pathways Microenvironment

项目摘要

DESCRIPTION (provided by applicant): Non-Hodgkin lymphoma (NHL) is the fifth most common cause of cancer death in the United States with a five-year survival rate of 64% overall (1996-03). Despite the promise of prognostic immune signatures, measurement of gene expression using microarrays is difficult in routine practice and evidence suggests that an exclusively genetic model is not sufficient to explain the outcome of NHL. Therefore, we propose to investigate tumor molecular markers that are routinely performed in pathology laboratory and lifestyle factors for their effects on NHL survival. Our Specific Aims are: 1) to compile a comprehensive database of epidemiologic data, clinical/laboratory prognostic factors, and treatments for NHL patients who participated in two existing case-control studies, 2) to determine the association of lifestyle factors (i.e., smoking, alcohol use, obesity, and intake of vegetables) with host microenvironment and tumor molecular markers (i.e., CD68, CD7, FOXP3, CD10, Ki67, LMO2, BCL6, BCL2, p53, and p21), 3) to investigate the association of lifestyle factors and host/tumor markers with clinical outcomes (relapse and survival), and 4) to determine which combination of markers are the most robust predictors of NHL outcome. To achieve these aims, we will develop a prognostic cohort using 722 patients of NHL (20 years or older) who participated in two population-based case-control studies in Nebraska (one from 1983-86 and the other from 1999-02) as the source of tissue samples, questionnaire data, and follow-up date. We have followed these patients though mid-2008 by abstracting data from the statewide Nebraska Lymphoma Registry and Tissue Bank database for clinical prognostic factors, treatments, and disease relapse and survival. We will perform immunohistochemical stains on existing tissue microarrays to detect tumor markers. The associations of lifestyle factors and tumor molecular markers with NHL survival will be evaluated using standard survival analysis. Because the study population is well-characterized and extensive epidemiologic and follow-up data as well as tissue microarrays have already been collected, the proposed study is cost-effective for addressing NHL outcome, one of the most common malignancies in the US. The results will provide new insights into improved disease prognostication, and ultimately lead to better treatment selection.

描述（由申请人提供）：非霍奇金淋巴瘤 (NHL) 是美国第五大最常见的癌症死亡原因，总体五年生存率为 64% (1996-03)。尽管有预后免疫特征的希望，但在常规实践中使用微阵列测量基因表达是困难的，并且证据表明仅遗传模型不足以解释 NHL 的结果。因此，我们建议研究病理实验室常规进行的肿瘤分子标记物和生活方式因素对 NHL 生存的影响。我们的具体目标是：1) 为参与两项现有病例对照研究的 NHL 患者编制流行病学数据、临床/实验室预后因素和治疗的综合数据库，2) 确定生活方式因素（即吸烟）之间的关联、饮酒、肥胖和蔬菜摄入）以及宿主微环境和肿瘤分子标记（即 CD68、CD7、FOXP3、CD10、Ki67、LMO2、 BCL6、BCL2、p53 和 p21)，3) 研究生活方式因素和宿主/肿瘤标志物与临床结果（复发和生存）的关联，以及 4) 确定哪种标志物组合是 NHL 结果最稳健的预测因子。为了实现这些目标，我们将使用 722 名 NHL 患者（20 岁或以上）开发一个预后队列，这些患者参加了内布拉斯加州的两项基于人群的病例对照研究（一项来自 1983-86 年，另一项来自 1999-02 年）：组织样本的来源、问卷数据和随访日期。我们从 2008 年中期开始对这些患者进行跟踪，从全州内布拉斯加州淋巴瘤登记处和组织库数据库中提取临床预后因素、治疗以及疾病复发和生存的数据。我们将对现有的组织微阵列进行免疫组织化学染色以检测肿瘤标志物。将使用标准生存分析来评估生活方式因素和肿瘤分子标志物与 NHL 生存的关联。由于研究人群特征明确，并且已经收集了广泛的流行病学和随访数据以及组织微阵列，因此拟议的研究对于解决 NHL（美国最常见的恶性肿瘤之一）的结果具有成本效益。研究结果将为改善疾病预测提供新的见解，并最终导致更好的治疗选择。