Energy balance and nutrigenetic analysis of non-Hodgkin lymphoma

非霍奇金淋巴瘤的能量平衡和营养遗传学分析

• 批准号: 8101263
• 负责人: Paige M. Bracci
• 金额: $ 7.49万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8101263
• 关键词: Accounting; Adult; Affect; Age; Apoptosis; Area; Ascorbic Acid; Behavioral; Body mass index; Case-Control Studies; Characteristics; Cholesterol Homeostasis; DNA; DNA Repair; Data; Data Set; Databases; Development; Diet; Dietary Factors; Dietary History; Dietary Practices; Dietary intake; Environmental Exposure; Epidemiologic Studies; Epidemiology; Exercise; Food; Food Supplements; Frequencies; Future; Gene-Modified; Genes; Genetic; Genetic Predisposition to Disease; Goals; Hematologic Neoplasms; Hereditary Disease; Immune; Immunosuppression; Incidence; Individual; Inflammation; Inflammatory; Inherited; Intake; Interview; Laboratories; Laboratory Research; Life Style; Logistic Regressions; Lymphomagenesis; Malignant Neoplasms; Medical; Metabolism; Methods; Micronutrients; Modification; Molecular Genetics; Natural Immunity; Newly Diagnosed; Non-Hodgkin' s Lymphoma; Nutrient; Obesity; Odds Ratio; Omega-3 Fatty Acids; Participant; Pathway interactions; Persons; Physical activity; Play; Population Study; Predisposition; Prevention program; Preventive Intervention; Process; Questionnaires; Relative (related person); Relative Risks; Risk; Risk Factors; Role; Sample Size; San Francisco; Screening procedure; Signal Transduction; Single Nucleotide Polymorphism; Statistical Methods; Subgroup; Survival Rate; Syndrome; Time; Tumor Necrosis Factor-alpha; Variant; Virus; Vitamin D; Woman; Work; adaptive immunity; case control; cooking; diet and exercise; energy balance; folic acid metabolism; gene environment interaction; genetic variant; immune function; improved; innovation; insight; intervention program; lifestyle factors; men; population based; programs; public health relevance; reactive oxygen intermediate; response; sex; uptake

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.

描述(申请人提供)：能量平衡和非霍奇金淋巴瘤的营养遗传学分析在美国，非霍奇金淋巴瘤(NHL)是成人中最常见的造血系统癌症，每年新诊断病例为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、锻炼和肥胖与NHL风险相关。实验室数据显示，这些因素还可以影响免疫和炎症过程，这些过程可能会影响淋巴肿大。NHL和NHL亚型的遗传易感性已经在生物学上被发现，包括免疫功能、炎症、氧化过程以及DNA修复和完整性。然而，还没有进行将能量平衡因素、遗传学和非霍奇金淋巴瘤风险相结合的全面分析。我们的创新分析将利用我们在大型人群病例对照研究(2055例，2081例对照)中亲自采访期间收集的流行病学和遗传学数据，以：目的1)分析饮食、人体测量和运动数据，以确定与NHL和NHL亚型风险的关联；目的2)分析基因与环境的相互作用，以确定饮食反应和代谢基因以及炎症和免疫功能基因中的单核苷酸多态(SNP)是否改变目标1中的因素与NHL风险之间的关联。经潜在混杂和效应修正调整后的非条件Logistic回归将用于获得相对风险估计的优势比，并探索包括NHL亚型在内的不同亚组的差异效应。还将使用能量调整方法和统计方法来评估食物频率问卷(FFQ)数据的错误报告，以分析营养数据。这项研究的主要优势是：1)丰富的流行病学数据集，包括已经收集的运动、人体测量学和饮食历史数据，使用经过验证和校准的FFQ收集的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品成分数据库计算的宏观和微量营养素；2)可用于评估混淆和效果修改的人口统计学和其他数据；3)已经分析了可能与NHL营养遗传学相关的生物途径中146个基因的SNPs的DNA。在我们定义明确的大型研究人群中进行的全面分析的结果将提供对与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的洞察，有助于阐明生物活性食品在淋巴肿大中的作用。我们的工作信息还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途径，并将直接应用于预防和干预计划，以减少NHL的发病率。此外，未来对这些数据和相关数据的联合分析计划在InterLymph Consortium内进行，以确认发现，并增加分析的能力和样本量，用于稀有NHL亚型的分析，以及在个别研究中无法充分调查的低频暴露。 公共卫生相关性：项目叙述非霍奇金淋巴瘤(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的遗传疾病有关的危险因素外，几乎没有确定的危险因素。越来越多的证据表明，饮食、体力活动和肥胖等可改变的生活方式因素与NHL风险有关，这些因素在遗传途径中发挥作用，也与NHL风险相关。阐明这些可改变因素在NHL和NHL亚型发病风险中的作用将提高我们对NHL发展的理解，有助于为未来的研究产生新的假说，并将直接适用于旨在降低NHL发病率的预防、干预和筛查计划。