Continuous Update Project: Mechanisms Framework Feasibility Testing

This feasibility study is also being conducted by Professor Rudolf Kaaks at the German Cancer Research Center (DKFZ)

  • Topic: Breast cancer
  • Institution: Maastricht University
  • Country: Netherlands
  • Status: Completed

Scientific abstract


In 2012 Dr Sarah Lewis and Prof Richard Martin, from the University of Bristol, received a grant to develop a novel methodology to systematically review mechanistic studies.

The independent Expert Panel working on our Continuous Update Project (CUP) – our ongoing analysis of worldwide research on the links between diet, weight, physical activity and cancer - had previously identified the need for a methodology to review this type of research that was as robust as the protocols used to carry out the systematic literature reviews (SLRs) of the epidemiological studies presented in the CUP Reports.

A special CUP Mechanisms Protocol Development Group was convened to develop some initial guidance on how to systematically review evidence on mechanisms and cancer. Following this guidance, and with input from World Cancer Research Fund International, the team at the University of Bristol developed a novel 2-stage framework to conduct systematic reviews to identify, appraise and synthesise the literature on mechanisms underlying pre-specified epidemiological associations between diet, nutrition and physical activity and cancer risk or progression.


Now that the framework has been finalised and peer reviewed, the next step is to test it. Two research teams - one from Maastricht University in the Netherlands and the other one from the German Cancer Research Center - have each received a grant (funded through our Request for Applications grant programme)  to ascertain the utility, feasibility and validity/reproducibility of the framework. The two research teams will independently apply the framework to identify the biological mechanisms underpinning the link between body fatness and postmenopausal breast cancer, and systematically review and assess the strength of the evidence underlying one specific mechanism.


The two research teams have brought together a set of multidisciplinary collaborators with expertise in systematic reviews, epidemiology, cancer biology, bioinformatics, statistics and project management. A wide range of expertise is needed to carry out the two different stages of the framework, and to be able to interpret the results.

During the application of stage 1 of the framework, the research teams will identify all potential mechanisms underlying the body fatness and postmenopausal breast cancer association, taking a largely ‘hypothesis-free’ approach. They will also test the new TeMMPo (Text Mining for Mechanism Prioritisation) web-based tool, which was developed to automate one of the steps in stage 1, and allows the visual representation of the potential mechanisms for a given exposure-outcome association by the quantity of evidence underlying each step in the mechanistic pathway.

For stage 2, the research teams will select, in agreement with each other, a specific mechanism underlying body fatness and postmenopausal breast cancer and systematically review the evidence for that particular mechanism. The teams will begin the research in November 2015 and will have seven months to complete the feasibility study. The team will present their findings at the 2016 CUP Panel meeting and provide the Panel with insights into how useful, clear and feasible the framework is, and the extent to which the findings are reproducible.

Grant publications