Diet patterns, aspirin use, obesity and multiple myeloma: a prospective analysis

饮食模式、阿司匹林使用、肥胖和多发性骨髓瘤：前瞻性分析

• 批准号: 9134664
• 负责人: BRENDA M BIRMANN
• 金额: $ 20.22万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9134664
• 关键词: Accounting; Address; Adult; Age; Aspirin; Body Size; Body Weight decreased; Body mass index; Calendar; Carbohydrates; Carcinogens; Cell membrane; Cessation of life; Chronic; Clinical; Clinical Data; Cohort Studies; Complement; Consumption; Data; Development; Diagnosis; Diet; Dietary Fiber; Dietary Practices; Disease; Epidemiology; Etiology; Evaluation; Fishes; Fruit; Growth; Habits; Health; Health Professional; Healthy Eating; Hematologic Neoplasms; Immune; Incidence; Inflammation; Inflammatory; Insulin-Like Growth Factor I; Intake; Interleukin-6; Life Style; Malignant Neoplasms; Medical History; Multiple Myeloma; National Cancer Institute; Neoplasms; Nuclear; Nurses' Health Study; Obesity; Participant; Pathogenesis; Pathway interactions; Patient risk; Patients; Pattern; Persons; Physiological; Population; Prevention; Prevention strategy; Processed Meats; Prospective Studies; Proxy; Public Health; Quality-Adjusted Life Years; Randomized; Reporting; Research; Research Personnel; Risk; Sample Size; Signal Transduction; Staging; Stratification; Survival Rate; Time; Treatment Protocols; United States; Update; Vegetables; base; cancer diagnosis; cancer type; circulating biomarkers; cohort; cost; cruciferous vegetable; design; differentiated B cell; follow-up; fruits and vegetables; improved; indexing; inflammatory marker; insight; interest; lifestyle factors; member; mortality; novel; novel therapeutics; outcome forecast; peripheral blood; polyunsaturated fat; prospective; sex; study population; tool

 DESCRIPTION (provided by applicant): Multiple myeloma (MM) poses a substantial public health, personal and financial burden. Novel therapies have enabled notable gains in MM survival in the past decade, but current United States 5- and 10-year relative survival rates show that MM remains lethal in most patients. Present understanding of MM etiology is inadequate to formulate risk stratification or prevention strategies. Even less is known regarding modifiable factors that could influence MM survival. The identification of lifestyle-based or other relatively inexpensive, accessible approaches to prolonging MM patient survival would further expand the tools available to clinicians and their patients. Inflammation and growth factor dysregulation contribute to MM pathogenesis, and thus it is plausible that potentially modifiable factors that modulate inflammatory or growth factor signaling may influence MM survival. The studies we propose in this application will examine three such plausible factors in the Nurses' Health Study (NHS) and Health Professionals Follow-up Study (HPFS) cohorts: diet quality (as captured by predefined, validated diet patterns), regular aspirin use and body mass index (BMI). Diet patterns have not, to our knowledge, been evaluated in relation to MM risk or survival. We previously observed a 39% reduction in MM risk in participants with higher quantity or duration of regular aspirin use and a 50% increased risk of MM in obese persons in the NHS and HPFS. Aspirin merits evaluation as a potential inexpensive complement to major treatment regimens to further improve MM survival in patients who can tolerate its use. The relation of obesity to MM survival also warrants clarification; usual adult obesity is positively associated with MM risk, bu obesity at MM diagnosis appears to confer a favorable prognosis, and short-term pre-diagnosis weight loss appears to be a better predictor of MM survival than BMI. With >25 years of follow-up and biennially updated, detailed information on these exposures and relevant covariates, and with projected sample sizes for the proposed studies of at least 400 MM patients (330 deaths), we are uniquely equipped in the NHS and HPFS to rigorously evaluate these potential predictors of MM risk and patient mortality. To address our limitation of incomplete clinical data on the MM patients, we also propose exploratory analyses of available clinical data, to aid the interpretation of the primary analyses and assess whether available variables (age, sex and calendar period, or a short survival time) may serve as a reasonable proxy when treatment or disease stage information is not available. These proposed studies will establish the first analyses of MM survival in the NHS and HPFS and guide the development and design of additional survival studies, including in large consortia where the project team has been instrumental in initiating pooled prospective studies on MM. As such, the proposed activities have strong potential to yield valuable insights for MM patients, clinicians and other investigators of MM and thus are likely to have high translational value over both the short- and longer-term to further diminish the burden of MM.

 描述（由适用提供）：多发性骨髓瘤（MM）构成了实质性的公共卫生，个人和金融伯恩。在过去的十年中，新型疗法在MM生存中取得了显着增长，但是当前美国的5年相对生存率表明，大多数患者的MM仍然致命。对MM病因的当前理解不足以制定风险分层或预防策略。关于可能影响MM生存的可修改因素，还知道少得多。基于生活方式或其他相对识别 延长MM患者生存的廉价，可访问的方法将进一步扩大临床医生及其患者可用的工具。炎症和生长因子失调有助于MM发病机理，因此，调节炎症或生长因子信号传导的潜在可修改因子可能会影响MM存活。我们在本申请中提出的研究将研究护士健康研究（NHS）和卫生专业人员随访研究（HPFS）同类中的三个此类合理因素：饮食质量（如预先定义，经过验证的饮食模式），常规的阿司匹林使用和体重指数（BMI）。据我们所知，饮食模式尚未得到与MM风险或生存有关的评估。我们先前观察到，常规阿司匹林使用量较高或持续时间的参与者的MM风险降低了39％，而NHS和HPF中肥胖者的MM风险增加了50％。阿司匹林值得评估作为对主要治疗方案的潜在廉价补充，以进一步改善能够忍受其使用的患者的MM存活率。肥胖与MM生存的关系也需要澄清；通常的成年肥胖与MM风险呈正相关，MM诊断的BU肥胖似乎赋予了有利的预后，而短期诊断前体重减轻似乎比BMI更好地预测了MM存活率。凭借> 25年的随访和每两年进行的更新，有关这些暴露和相关的协变量的详细信息，并且预计的样本量对于至少400毫米患者（330例死亡）的拟议研究的样本量，我们在NHS和HPF中与MM风险和患者的潜在预测率严格评估了我们在NHS和HPF中的等效性。为了解决我们对MM患者不完整的临床数据的局限性，我们还建议对可用临床数据进行探索性分析，以帮助解释主要分析并评估是否可用的变量（年龄，性别和短期生存期或短期生存时间）可以作为治疗或疾病阶段信息的合理代理。这些提出的研究将在NHS和HPF中建立对MM生存的首次分析，并指导其他生存研究的开发和设计，包括在项目团队在启动MM的汇总前瞻性研究中发挥作用的大型财团。因此，拟议的活动具有强大的潜力，可以为MM患者，临床医生和其他MM研究人员提供宝贵的见解，因此在短期和长期内可能具有很高的转化价值，以进一步减少MM的燃烧。