Linking diet, nutrition and physical activity to cancer: a systematic review framework for integrating evidence from human, animal and other mechanistic studies

Sarah Lewis1

1University of Bristol, Bristol, UK


Background: Many laboratory experiments are performed to identify causal pathways and in doing so inform human health. These mechanistic studies complement epidemiological findings and can offer insights into biological plausibility and pathways between exposure and disease. Systematic reviews are the most robust way to synthesise data which have addressed a common question. Methods for conducting and reporting rigorous systematic reviews of epidemiological studies are well established. However, such methods are lacking for mechanistic studies. We were commissioned by the WCRF to develop a protocol for conducting systematic reviews of mechanistic studies which underpin epidemiological associations between exposures and cancer.

Methods: A multidisciplinary team with expertise in informatics, statistics, epidemiology, systematic reviews, cancer biology and nutrition was assembled and a series of 5 one-day workshops took place involving presentations, group work and discussions, along with smaller meetings and research being carried out in the intervening periods.

Results: We have developed a template for carrying out rigorous systematic reviews of mechanistic studies, which includes guidance on; a two stage search strategy, (the first stage of which is a mechanisms discovery search, followed by a targeted search for studies on a specific mechanism), formulating a research question, applying inclusion/exclusion criteria, assessing the relevance of retrieved studies to the research question, assessing the quality of individual studies (using appropriate risk of bias tools), synthesizing the data from individual studies, assessing the strength of the overall body of evidence from human and animal studies separately and integrating the human and animal studies to reach a conclusion.

Conclusion: The above template will be available to researchers in the future who wish to conduct robust systematic reviews of the mechanisms which underpin associations between exposures and cancer.


Funding: World Cancer Research Fund (WCRF)