Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 1667-1675 |
| Number of pages | 9 |
| Journal | Cancer Epidemiology Biomarkers and Prevention |
| Volume | 26 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Nov 2017 |
Bibliographical note
Funding Information:T.R. Gaunt reports receiving commercial research grants from Biogen, GlaxoSmithKline, and Sanofi. S.D. Turner reports receiving a commercial research grant from GlaxoSmithKline. No potential conflicts of interest were disclosed by the other authors.
Funding Information:
All authors received a grant from the World Cancer Research Fund (grant number: RFA 2012/620). S. Harrison is a Wellcome Trust Funded PhD student, 102432/Z/13/Z. R.M. Martin, S.J. Lewis, J.M.P. Holly, T. Gaunt, C.M. Perks are supported by a Cancer Research UK (C18281/A19169) Programme Grant (the Integrative Cancer Epidemiology Programme).
Funding Information:
We approached colleagues and collaborators from the University of Bristol (Bristol, United Kingdom), University of Cambridge (Cambridge, United Kingdom), and the International Agency for Research on Cancer (Lyon, France) to assemble a multidisciplinary team with expertise in bioinformatics (T.R. Gaunt), statistics (J. Higgins, S. Harrison, K. Northstone, and R.M. Martin), cancer biology (J.M.P. Holly, C.M. Perks, and S. Thomas), animal studies (J.M.P. Holly, M. Gardner, and S. Thomas), molecular biology (T.R. Gaunt, J.M.P. Holly, C.M. Perks, V. Tan, and S. Thomas), epidemiology (S.J. Lewis, P. Emmett, M. Jeffreys, K. Northstone, and R.M. Martin), genetic epidemiology (S.J. Lewis and T.R. Gaunt), nutrition (S. Rinaldi, P. Emmett, and K. Northstone), and systematic reviews (S.J. Lewis, M. Gardner, J. Higgins, and R.M. Martin). Our objective to develop a rigorous systematic review methodology integrating animal, cell, and human studies was met through a combination of discussion workshops and advice from a panel of experts. Decisions were reached by discussion and consensus opinion and then tested in practice. Results were fed back to the team, and changes were made to the methodology if needed.
Publisher Copyright:
©2017 AACR.
Funding
T.R. Gaunt reports receiving commercial research grants from Biogen, GlaxoSmithKline, and Sanofi. S.D. Turner reports receiving a commercial research grant from GlaxoSmithKline. No potential conflicts of interest were disclosed by the other authors. All authors received a grant from the World Cancer Research Fund (grant number: RFA 2012/620). S. Harrison is a Wellcome Trust Funded PhD student, 102432/Z/13/Z. R.M. Martin, S.J. Lewis, J.M.P. Holly, T. Gaunt, C.M. Perks are supported by a Cancer Research UK (C18281/A19169) Programme Grant (the Integrative Cancer Epidemiology Programme). We approached colleagues and collaborators from the University of Bristol (Bristol, United Kingdom), University of Cambridge (Cambridge, United Kingdom), and the International Agency for Research on Cancer (Lyon, France) to assemble a multidisciplinary team with expertise in bioinformatics (T.R. Gaunt), statistics (J. Higgins, S. Harrison, K. Northstone, and R.M. Martin), cancer biology (J.M.P. Holly, C.M. Perks, and S. Thomas), animal studies (J.M.P. Holly, M. Gardner, and S. Thomas), molecular biology (T.R. Gaunt, J.M.P. Holly, C.M. Perks, V. Tan, and S. Thomas), epidemiology (S.J. Lewis, P. Emmett, M. Jeffreys, K. Northstone, and R.M. Martin), genetic epidemiology (S.J. Lewis and T.R. Gaunt), nutrition (S. Rinaldi, P. Emmett, and K. Northstone), and systematic reviews (S.J. Lewis, M. Gardner, J. Higgins, and R.M. Martin). Our objective to develop a rigorous systematic review methodology integrating animal, cell, and human studies was met through a combination of discussion workshops and advice from a panel of experts. Decisions were reached by discussion and consensus opinion and then tested in practice. Results were fed back to the team, and changes were made to the methodology if needed.
ASJC Scopus subject areas
- Epidemiology
- Oncology
