About the Branch
Overview
A substantial portion of malignant disease is likely due to diet, obesity, and physical inactivity --NAS, WHO, IARC
NEB's goal is clarifying the nutritional etiology of cancer. Many studies have implicated diet and other nutritional exposures in carcinogenesis and it is widely believed that nutrition is causally related to malignant disease. Nevertheless, when it comes to cancer etiology, the evidence for nutrition is less convincing than that for other exposures (radiation, viruses, and chemicals, for example). Many fundamental diet-and-cancer questions remain unresolved. NEB, therefore, conducts independent and collaborative research intended to raise qualitatively the level of evidence that nutritional factors cause cancer.
The Branch currently focuses on four broad exposure-driven hypotheses 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, including the role of folate and certain B vitamins; 4) meat consumption, 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 also incorporate DNA-based genetic information. Because of the extensive biological research underlying contemporary nutrition, we frequently develop multidisciplinary studies with metabolic and 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:
- 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 researchers 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 investigators tackle 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).
- Inadequate exposure range: Relative dietary homogeneity within study populations may hinder investigators' ability to make important dietary intake comparisons. In that vein, NEB has developed several investigations, including the NIH-AARP Diet and Health Study), the nutrition component of the and the India cohort feasibility study, with wide reported intakes ranges for several key dietary factors.
- 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 (PPT), the Alpha-Tocopherol Beta-Carotene (ATBC) Study, and the Selenium and Vitamin E Cancer 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 (as well as measurement error) than an association with the dietary factor itself.
