Mechanisms research

Innovative methodology to review research on mechanisms by which lifestyle factors may cause cancer

Our panel for the Continuous Update Project (CUP) identified a gap in the knowledge of mechanistic evidence to support causal relationships between nutrition, physical activity and cancer. Recognising the importance of mechanistic evidence to strengthen the epidemiological evidence, we commissioned research to develop a methodology to systematically review the vast number of mechanistic studies that underpin diet and cancer associations. The aim was to ensure that the methodology to review mechanistic research was as robust as the protocols used to carry out the systematic literature reviews of the epidemiological studies analysed for our CUP.

The team, led by Dr Sarah Lewis and Professor Richard Martin, developed a new framework for assessing mechanistic studies, including an automated mechanisms discovery search tool known as TeMMPo (Text Mining for Mechanism Prioritisation).

Dr Giota Mitrou, Director of Research Funding and Science External Relations at World Cancer Research Fund, said of the framework: “This exciting new methodology has the potential to become the mainstream approach to review mechanistic studies. It also offers a platform to inform the direction of future research in the area of diet, nutrition, physical activity and cancer.”

Two independent research groups have tested the framework to determine its utility, feasibility and reproducibility to systematically review evidence on mechanisms and cancer. The two teams independently applied the framework to identify the biological mechanisms underpinning the link between body fatness and postmenopausal breast cancer, and systematically reviewed and assessed the strength of the evidence underlying one specific mechanism.

The two feasibility study teams concluded that the framework is a good starting point for conducting systematic reviews by integrating evidence from mechanistic studies on exposure-cancer associations. Work to develop a systematic process that is feasible in terms of time and cost for reviewing the evidence from experimental studies for the CUP is continuing.