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Diet and cancer prevention: the roles of observation and experimentation

Nature Reviews Cancer volume 8, pages 694–703 (2008)Cite this article

Key Points

  • Chemoprevention is defined as the use of pharmacological agents (including nutrients) to impede, arrest or reverse carcinogenesis and has been used to test the efficacy of numerous nutrients and other dietary factors.

  • Observational epidemiology and experimentation by randomized controlled trials (RCTs) have been used to evaluate dietary factors in cancer chemoprevention; however, consistency in findings has been elusive.

  • The study of diet and cancer associations in humans poses a variety of challenges owing to the complexity in measuring dietary intake as well as the multifactorial nature of the cancer endpoints.

  • In several circles, RCTs are viewed as being more credible than observational studies.

  • When discrepant results between observational studies and RCTs are reported, careful consideration needs to be given to the details of each set of studies before accepting RCTs as valid and those of observational studies as biased.

  • Considerations in the interpretation of results from RCTs include the background diet of the study population; the dose, duration and timing of the intervention; the precise form of the nutrient or dietary factor tested; and compliance with the intervention.

Abstract

Observational epidemiology and experimentation by randomized controlled trials (RCTs) have been used to evaluate dietary factors in cancer prevention; however, consistency in findings has been elusive. In several circles, RCTs are viewed as more credible than observational studies. As the testing of dietary epidemiological findings in RCTs has been more common for colorectal cancer than for other cancers, we use experience with this malignancy to critically appraise the reasons for discrepancies between results of observational and experimental studies.

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Figure 1: Randomized controlled trials (RCTs) versus observational studies of cancer.
Figure 2: Ranges of nutrient intakes tested in observational and randomized controlled trials (RCTs) of calcium and fibre.
Figure 3: Randomized controlled trials (RCTs) of colorectal adenomas.

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Authors and Affiliations

  1. Arizona Cancer Center, 1515 North Campbell Avenue

    María Elena Martínez

  2. University of Arizona, Tucson, 85724, Arizona, USA

    María Elena Martínez

  3. Mel and Enid Zuckerman Arizona College of Public Health, 1295 North Martin Avenue

    María Elena Martínez

  4. University of Arizona, Tucson, 85724, Arizona, USA

    María Elena Martínez

  5. Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo, 14263, New York, USA

    James R. Marshall

  6. Departments of Nutrition and Epidemiology, Harvard School of Public Health, 665 Huntington Avenue, Boston, 02115, Massachusetts, USA

    Edward Giovannucci

  7. Department of Medicine, Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, 02115, Massachusetts, USA

    Edward Giovannucci

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  1. María Elena Martínez
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Correspondence to María Elena Martínez.

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Glossary

Confounder

A factor that is associated with both an exposure factor and disease outcome such that it distorts or masks the true effect of exposure in an epidemiological study.

Colonoscopy

A procedure usually performed by a gastroenterologist that allows him/her to look inside the colon.

Polypectomy

Removal of one or more polyps, usually by colonoscopy.

Metachronous adenomas

Multiple separate adenomas developing at different intervals.

Adenoma recurrence

A model commonly used to test chemopreventive properties of a variety of agents. Study participants include individuals who have undergone colonoscopy and polypectomy of all lesions visualized and are followed prospectively for the development of metachronous and/or recurrent adenomas.

Polyglutamation

The addition of multiple glutamic acid residues by an enzymatic process. The polyglutamated folates have greater metabolic activity and are retained better in cells.

Ispaghula husk

Also known as psyllium, this is a bulk-forming laxative used to treat constipation and is a dietary source of soluble fibre.

Natural killer cells

A type of lymphocyte that attacks and kills tumour cells and protects against infectious microbes. The term 'natural' is used because they do not need additional stimulation in order to attack and kill.

Hyperinsulinaemia

The presence of an abnormally high level of insulin in the blood. This is usually caused by insulin resistance, a condition in which the body cannot use insulin properly.

Glycaemic load

An indicator of glucose response or insulin demand that is induced by total carbohydrate intake. It is calculated by multiplying the weighted mean of the dietary glycaemic index by the percentage of total energy from carbohydrate.

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Martínez, M., Marshall, J. & Giovannucci, E. Diet and cancer prevention: the roles of observation and experimentation. Nat Rev Cancer 8, 694–703 (2008). https://doi.org/10.1038/nrc2441

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