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）是美国第五大最常见的癌症死亡原因，总体5年生存率为64%（1996-03）。尽管预后免疫特征有希望，但在常规实践中使用微阵列测量基因表达是困难的，有证据表明，一个专门的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检测的肿瘤分子标记和生活方式因素对NHL生存的影响。我们的具体目标是：1)建立两项现有病例对照研究中NHL患者的流行病学资料、临床/实验室预后因素和治疗方法的综合数据库；2)确定生活方式因素（如吸烟、饮酒、肥胖和蔬菜摄入）与宿主微环境和肿瘤分子标志物（如CD68、CD7、FOXP3、CD10、Ki67、LMO2、BCL6、BCL2、p53和p21）的关系；3)研究生活方式因素和宿主/肿瘤标志物与临床预后（复发和生存）的关系，以及4)确定哪种标志物组合是NHL预后最可靠的预测因子。为了实现这些目标，我们将建立一个预后队列，使用722名NHL患者（20岁或以上），他们参加了内布拉斯加州两项基于人群的病例对照研究（一项从1983-86年开始，另一项从1999- 2002年开始）作为组织样本、问卷数据和随访日期的来源。我们通过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、疾病复发和生存的数据，跟踪这些患者至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记物与NHL生存的关系将使用标准生存分析进行评估。由于研究人群具有良好的特征，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结果具有成本效益，NHL是美国最常见的恶性肿瘤之一。该结果将为改善疾病预后提供新的见解，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.