Developing the WCRF international/University of Bristol methodology for identifying and carrying out systematic reviews of mechanisms of exposure-cancer associations

Research output: Contribution to journalArticlepeer-review


  • Sarah J Lewis
  • Julian Higgins
  • Jeff M P Holly
  • Tom R Gaunt
  • Claire M Perks
  • Suzanne D Turner
  • Sabina Rinaldi
  • Steve Thomas
  • Sean Harrison
  • Rosie J Lennon
  • Vanessa Tan
  • Cath Borwick
  • Pauline Emmett
  • Mona Jeffreys
  • Kate Northstone
  • Giota Mitrou
  • Martin Wiseman
  • Rachel Thompson
  • Richard M Martin

Colleges, School and Institutes

External organisations

  • University of Bristol
  • University Hospitals Bristol NHS Foundation Trust
  • University of Cambridge
  • International Agency for Research on Cancer
  • University Hospital of Wales
  • WCRF International


Background: Human, animal, and cell experimental studies; human biomarker studies; and genetic studies complement epidemiologic findings and can offer insights into biological plausibility and pathways between exposure and disease, but methods for synthesizing such studies are lacking. We, therefore, developed a methodology for identifying mechanisms and carrying out systematic reviews of mechanistic studies that underpin exposure-cancer associations.

Methods: A multidisciplinary team with expertise in informatics, statistics, epidemiology, systematic reviews, cancer biology, and nutrition was assembled. Five 1-day workshops were held to brainstorm ideas; in the intervening periods we carried out searches and applied our methods to a case study to test our ideas.

Results: We have developed a two-stage framework, the first stage of which is designed to identify mechanisms underpinning a specific exposure-disease relationship; the second stage is a targeted systematic review of studies on a specific mechanism. As part of the methodology, we also developed an online tool for text mining for mechanism prioritization (TeMMPo) and a new graph for displaying related but heterogeneous data from epidemiologic studies (the Albatross plot).

Conclusions: We have developed novel tools for identifying mechanisms and carrying out systematic reviews of mechanistic studies of exposure-disease relationships. In doing so, we have outlined how we have overcome the challenges that we faced and provided researchers with practical guides for conducting mechanistic systematic reviews.

Impact: The aforementioned methodology and tools will allow potential mechanisms to be identified and the strength of the evidence underlying a particular mechanism to be assessed. Cancer Epidemiol Biomarkers Prev; 26(11); 1667-75. ©2017 AACR.

Bibliographic note

©2017 American Association for Cancer Research.


Original languageEnglish
Pages (from-to)1667-1675
Number of pages9
JournalCancer Epidemiology, Biomarkers & Prevention
Issue number11
Early online date4 Oct 2017
Publication statusPublished - Nov 2017


  • Biomedical Research/methods, Data Mining/methods, Evidence-Based Medicine/methods, Humans, Intersectoral Collaboration, Neoplasms/diagnosis, Research Design

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