Impact of Lifestyle with Tumor Pathways and Microenvironment on Lymphoma Survival

描述（由申请人提供）：非霍奇金淋巴瘤（NHL）是美国癌症死亡的第五大常见原因，总体五年生存率为64%（1996-03）。尽管预后免疫签名的承诺，使用微阵列的基因表达的测量是困难的，在常规实践和证据表明，一个专门的遗传模型是不足以解释NHL的结果。因此，我们建议调查的肿瘤分子标记物，常规进行病理实验室和生活方式因素对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、饮酒、肥胖和蔬菜摄入）与宿主微环境和肿瘤分子标志物（即，CD 68、CD 7、FOXP 3、CD 10、Ki 67、LMO 2、BCL 6、BCL 2、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（复发和存活）的关联，和4）确定哪种标志物组合是NHL结果的最稳健预测因子。为了实现这些目标，我们将开发一个预后队列，使用722例NHL患者（20岁或以上），他们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），作为组织样本、问卷数据和随访日期的来源。我们通过从内布拉斯加州淋巴瘤登记处和组织库数据库中提取数据，跟踪这些患者的临床预后因素、治疗方法、疾病复发和生存率，直至2008年年中。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。生活方式因素和肿瘤分子标志物与NHL生存率的相关性将使用标准生存分析进行评估。由于研究人群特征良好，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结局（美国最常见的恶性肿瘤之一）具有成本效益。这些结果将为改善疾病诊断提供新的见解，并最终导致更好的治疗选择。

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.