Energy balance and nutrigenetic analysis of non-Hodgkin lymphoma

描述（申请人提供）：非霍奇金淋巴瘤的能量平衡和营养分析在美国，非霍奇金淋巴瘤（NHL）是成人中最常见的造血系统癌症，每年新诊断的病例超过60，000例。一些研究已经确定了能量平衡的一些组成部分：饮食，运动和肥胖与NHL风险相关。实验室数据表明，这些因素也可以影响免疫和炎症过程，可能会影响淋巴瘤的发生。NHL和NHL亚型的遗传易感性已在生物学上合理的途径中确定，包括免疫功能、炎症、氧化过程以及DNA修复和完整性。然而，没有进行综合分析，整合能量平衡因素，遗传学和NHL风险。我们的创新分析将利用我们的大型人群病例对照NHL研究中已经收集的流行病学和遗传学数据（2055例，2081例对照）：目的1）分析饮食、人体测量和运动数据，以确定与NHL及其亚型风险的关系;目的2）分析基因与环境的交互作用，确定饮食反应和代谢基因的单核苷酸多态性（SNP），在炎症和免疫功能基因中，Aim 1和NHL风险因素之间的关联被修改。将使用针对潜在混杂因素和效应修正进行调整的非条件logistic回归获得比值比作为相对风险的估计值，并探索包括NHL亚型在内的亚组的差异效应。评估食物频率问卷（FFQ）数据误报的能量调整方法和统计方法也将用于营养数据分析。该研究的主要优势是：1）丰富的流行病学数据集，包括已经收集的运动，人体测量学和饮食史数据，这些数据是使用经过验证和校准的FFQ收集的，FFQ具有特定食物的频率和份量，补充剂的使用，烹饪方法以及使用相关食物成分数据库计算的宏量和微量营养素; 2）人口统计学和其他数据可用于评估混淆和影响修正; 3）已经在可能与NHL的营养遗传学相关的生物学途径中的146个基因中分析了SNP的DNA。在我们大型明确定义的研究人群中进行全面分析的结果将深入了解与NHL和常见NHL亚型相关的可改变的饮食相关风险因素和营养遗传学，这有助于澄清生物活性食物在淋巴瘤发生中的作用。从我们的工作中获得的信息也将有助于为未来的研究产生假设，指导功能研究，帮助确定改变易感性的关键生物学途径，并将直接适用于预防和干预计划，以减少NHL的发病率。此外，InterLymph Consortium计划对这些数据和相关数据进行未来的汇总分析，以确认结果，并增加罕见NHL亚型分析的把握度和样本量，以及无法在个体研究中充分研究的低频暴露。 公共卫生相关性：非霍奇金淋巴瘤（NHL）的发病率在过去40年中几乎翻了一番，除了与严重免疫抑制和一些罕见遗传疾病相关的风险因素外，几乎没有其他风险因素。越来越多的证据表明，饮食，体育活动和肥胖等可改变的生活方式因素与NHL风险相关，并且这些因素在与NHL风险相关的遗传途径中起作用。阐明这些可变因素在NHL和NHL亚型风险中的作用将提高我们对NHL发展的理解，有助于为未来研究产生新的假设，并将直接适用于预防，干预和筛查计划，以降低NHL发病率。

DESCRIPTION (provided by applicant): Energy balance and nutrigenetic analyses of non-Hodgkin lymphoma In the U.S, non-Hodgkin lymphoma (NHL) is the most common hematopoietic cancer in adults with >60,000 cases newly diagnosed each year. A few studies have identified some components of energy-balance: diet, exercise and obesity that are associated with NHL risk. Laboratory data show that these factors also can affect immune and inflammatory processes that may influence lymphomagenesis. Genetic susceptibility for NHL and NHL subtypes has been identified in biologically plausible pathways including immune function, inflammation, oxidative processes and in DNA repair and integrity. However, no comprehensive analyses have been conducted that integrate energy-balance factors, genetics and NHL risk. Our innovative analyses will leverage epidemiologic and genetic data already collected during in-person interviews in our large population-based case-control NHL study (2055 cases, 2081 controls) to: Aim 1) analyze diet, anthropometric and exercise data to determine associations with risk of NHL and NHL subtypes and; Aim 2) analyze gene-environment interactions to determine if single nucleotide polymorphisms (SNP) in dietary response and metabolism genes, and in inflammation and immune function genes modify the association between factors in Aim 1 and NHL risk. Unconditional logistic regression adjusted for potential confounding and effect modification will be used to obtain odds ratios as estimates of relative risk and to explore differential effects by subgroups including NHL subtypes. Energy-adjusted methods and statistical methods to assess misreporting of food frequency questionnaire (FFQ) data also will be used for analyses of nutrient data. The studys major strengths are: 1) a rich epidemiologic dataset that includes already collected exercise, anthropometrics and dietary history data collected using a validated and calibrated FFQ with frequency and portion size for specific foods, supplement use, cooking methods and macro and micronutrients computed using a relational food composition database; 2) demographic and other data available to evaluate confounding and effect modification and; 3) DNA already analyzed for SNPs in 146 genes in biologic pathways that may be relevant to the nutrigenetics of NHL. Results from the comprehensive analyses within our large well-defined study population will provide insight into modifiable dietary-related risk factors and nutrigenetics associated with NHL and common NHL subtypes that can help clarify the role of bioactive foods in lymphomagenesis. The information from our work also will be useful to help generate hypotheses for future research, to direct functional studies, to help identify key biologic pathways that alter susceptibility, and will be directly applicable to prevention and intervention programs to reduce NHL incidence. In addition, future pooled analyses of these and related data are planned within the InterLymph Consortium to confirm findings and to increase power and sample size for analyses by rare NHL subtypes, and for low-frequency exposures that cannot be investigated adequately in individual studies. PUBLIC HEALTH RELEVANCE: Project Narrative Incidence of non-Hodgkin lymphoma (NHL) has nearly doubled over the past 40 years and few risk factors have been established other than those associated with severe immunosuppression and some rare genetic conditions. There is growing evidence that the modifiable lifestyle factors of diet, physical activity and obesity are associated with NHL risk and that these factors act in genetic pathways that also have been associated with NHL risk. Clarifying the role that these modifiable factors play in risk of NHL and NHL subtypes will improve our understanding of NHL development, help to generate new hypotheses for future research and will be directly applicable to prevention, intervention and screening programs with a goal to reduce NHL incidence.