Etiologic Studies of Diet and Cancer

饮食与癌症的病因学研究

• 批准号: 8157915
• 负责人: Arthur Schatzkin
• 金额: $ 52.97万
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8157915
• 关键词: diet and cancer

Dietary exposures are believed to contribute to the majority of human cancers although most of the specific causal factors have not yet been identified. Since diet is a universal and modifiable exposure, research in this area offers the opportunity of significantly reducing cancer incidence and mortality. The Nutritional Epidemiology Branch conducts independent and collaborative research on the role of diet and nutritional status in cancer etiology. The Branch seeks to generate and test specific nutritional hypotheses, providing a scientific basis for public health recommendations and further understanding of the molecular basis of carcinogenesis. The Branch currently focuses on four broad exposure-drivenhypotheses involving: 1) energy balance (obesity and physical activity); 2) hyperinsulinemia and insulin resistance (taken broadly to include glycemic index and the IGF axis); 3) one-carbon metabolism; 4) meat, including potentially carcinogenic products of processing and cooking. The Branch also investigates other macronutrients and foods (fat, fiber, fruits and vegetables,) as well as micronutrients (vitamins D, E; calcium; selenium; carotenoids). Branch investigations in these priority areas use data on diet, supplement use, body size, physical activity, and blood- and tissue-based analytes. Many of these studies are also incorporate DNA-based genetic information. Because of the extensive biological research underlying contemporary nutrition, we frequently develop multidisciplinary studies with metabolic and/or molecular components. The role of nutrition is currently being evaluated in studies of lung, esophageal, stomach, colorectal, breast, endometrial, cervical, and prostate cancers as well as non-Hodgkin's lymphoma. Research approaches include descriptive analyses to generate hypotheses, analytic cohort and case-control investigations (with increasing emphasis on large prospective studies), nutritional intervention studies (clinical trials), metabolic studies, and biologic marker and genetic susceptibility projects. The Branch research program is designed to overcome several scientific obstacles to advancing the field: 1) Exposure assessment error. NEB, in conjunction with other NCI Divisions and other investigators around the world, has been conducting a series of methodologic studies to determine if we are missing key nutrition-cancer relations because of food frequency questionnaire measurement error and whether we need to use more intensive (and expensive) but more accurate assessment instruments. NEB is also expanding its work in nutrition-gene interactions. As we work through the problem of gene/SNP/haplotype selection in the face of complex biochemical pathways, NEB?s expanding work in nutrition-gene interactions can reveal ?sharpened? relative risks among the genetically susceptible (e.g., those with a particular allelic variant of a metabolizing enzyme-encoding gene) and thereby clarify the role of particular nutritional factors (alone or as part of complex dietary mixtures). 2) Inadequate exposure range. NEB?s investigations include existing (AARP, PLCO) and proposed (India) cohorts with wide reported intakes ranges for several key dietary factors. 3) Confounding. Relative risks for many nutritional factors are likely to be modest and easily confounded, even with adjustment for covariates. NEB approaches to this problem include: a) conducting or collaborating on randomized controlled trials, e.g., Polyp Prevention Trial, SELECT; b) using ?Mendelian randomization?, a strategy based on the premise that an association between an allelic variant mimicking, e.g., low micronutrient exposure is less likely to be biased by confounding (and measurement error) than an association with the dietary factor itself.

尽管尚未确定大多数特定的因果因素，但据信饮食暴露会导致大多数人类癌症。由于饮食是一种普遍且可修改的暴露，因此该领域的研究提供了显着降低癌症发病率和死亡率的机会。营养流行病学分支对饮食和营养状况在癌症病因中的作用进行独立和协作研究。 该分支机构旨在产生和检验特定的营养假设，为公共卫生建议提供科学基础，并进一步了解癌变的分子基础。该分支目前侧重于四个涉及的四个广泛暴露驱动的型：1）能量平衡（肥胖和体育锻炼）； 2）高胰岛素血症和胰岛素抵抗（广泛地包括血糖指数和IGF轴）； 3）一种碳代谢； 4）肉，包括加工和烹饪的潜在致癌产品。该分支还研究了其他大型营养素和食物（脂肪，纤维，水果和蔬菜）以及微量营养素（维生素D，E;钙；硒；类胡萝卜素）。这些优先区域的分支研究使用饮食，补充使用，体型，体育锻炼以及基于血液和组织分析物的数据。这些研究中的许多也包含基于DNA的遗传信息。由于当代营养的广泛生物学研究，我们经常通过代谢和/或分子成分进行多学科研究。营养的作用目前正在肺，食管，胃，结直肠癌，乳房，子宫内膜，宫颈和前列腺癌以及非霍奇金淋巴瘤的研究中评估。研究方法包括描述性分析以产生假设，分析队列和病例对照研究（越来越重视大型前瞻性研究），营养干预研究（临床试验），代谢研究，生物学标记和遗传易感性项目。 分支研究计划旨在克服一些科学障碍来推进该领域：1）暴露评估错误。 NEB与其他NCI部门和世界各地的其他研究人员一起进行了一系列方法论研究，以确定由于食品频率问卷的测量错误以及我们是否需要使用更强化（和更昂贵的）但更准确的评估工具，我们是否缺少关键的营养关系。 NEB还在扩大其在营养 - 基因相互作用中的工作。当我们通过复杂的生化途径中的基因/SNP/单倍型选择问题时，NEB在营养 - 基因相互作用中的扩展工作可以揭示吗？遗传易感性的相对风险（例如，具有代谢酶编码基因的特定等位基因变体的风险），从而阐明了特定的营养因子（单独或作为复杂饮食混合物的一部分）的作用。 2）暴露范围不足。 NEB的调查包括现有的（AARP，PLCO）和拟议的（印度）同类，其中有几种关键饮食因素的摄入量广泛。 3）混淆。许多营养因素的相对风险也可能是适度的，并且很容易混淆，即使对协变量进行了调整。 NEB解决此问题的方法包括：a）进行或合作进行随机对照试验，例如息肉预防试验，选择； b）使用“孟德尔随机化？”，一种基于以下前提的策略，即模仿的等位基因变体之间的关联，例如，低微量营养素暴露不到与与饮食因素本身的关联的混杂（和测量误差）的偏见。