WASHINGTON, D.C. — A multidisciplinary team of 20 scientists came together to develop an innovative method to systematically assess the vast numbers of mechanistic studies linked to cancer risk. The framework provides a groundbreaking approach for testing the links seen in human studies between lifestyle factors and cancer, which are set out in systematic reviews of the research by the American Institute for Cancer Research (AICR) and World Cancer Research Fund (WCRF). The new method promises to accelerate the process of understanding the biological details of how common lifestyle factors can lead to or prevent cancer.
The new tool was tested in a case study and the paper was published in Cancer Epidemiology, Biomarkers & Prevention. It was funded by World Cancer Research Fund. A poster presentation on this new methodology is being held at the Obesity and Cancer: Mechanisms Underlying Etiology and Outcomes Conference in Austin, Texas by Dr. Nigel Brockton, Director of Research at AICR.
Dr. Sarah Lewis, Senior Lecturer in Genetic Epidemiology at University of Bristol, one of the lead researchers on the new tool says, “This is an important step for cancer research. It will enable researchers to realistically assess the science so that we can exploit what we know and focus future studies on addressing progress-limiting gaps.”
The framework builds on AICR/WCRF systematic reviews of human studies, which analyze how different cancers link to diet, physical activity and body weight. Mechanistic explanations are a key part of determining the plausibility and strength of an observed link yet, until now, there has been no systematic process to identify and assess the strength of this research. Scientists have typically searched the literature and then describe the state of the science in a narrative review. Mechanistic studies include human, animal, cell, human biomarker and genetic association studies and there are often tens of thousands of potentially relevant studies for one link.
“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,” said, Dr. Giota Mitrou, Director of Research Funding & Science External Relations at World Cancer Research Fund International.
A multidisciplinary team of experts in informatics, statistics, epidemiology, systematic reviews, cancer biology and nutrition worked together on the framework. The team developed a two-phase strategy. Phase one uses an automated online tool (‘Text Mining for Mechanism Prioritisation’ – TeMMPo) to rank all potential mechanisms that link a dietary or another factor to the disease. Phase two then systematically reviews and assesses the strength of the evidence for any one particular mechanism.
Fundamental to phase one is an automated online tool (‘Text Mining for Mechanism Prioritisation’, TeMMPo) that ranks and visualizes the amount of evidence underlying steps along the mechanistic pathway. The new tool pulls from search terms that include a list of intermediate phenotypes (IPs) between the risk factor and cancer. IPs are observable characteristics, such as DNA damage. Animal and other mechanistic studies commonly have IPs as an outcome rather than cancer.
“The process searches for studies that look at exposure to the risk factor and how this influences an IP, and also studies of the same IP and how this affects an outcome [such as cancer],” said Lewis.
Assessing the quality of the studies is also a key part of the framework.
Lewis says, “The methodology and tools that we have developed could identify interesting biological pathways which may explain how a lifestyle or dietary factor causes cancer and assesses the weight of the evidence underlying a particular biological mechanism.”
The conclusion is that there are gaps that need to be filled but awareness of those gaps is the first step in addressing them.
“This project is a major reality check; it’s like ripping off a Band Aid,” said Brockton. “The creation of this framework shows that it is possible to apply objective approaches to assess the available mechanistic research, which will accelerate the recognition of gaps in our knowledge.”
Source: Developing the WCRF International/University of Bristol Methodology for Identifying and Carrying Out Systematic Reviews of Mechanisms of Exposure–Cancer Associations
Sarah J. Lewis, Mike Gardner, Julian Higgins, Jeff M.P. Holly, Tom R. Gaunt, Claire M. Perks, Suzanne D. Turner, Sabina Rinaldi, Steve Thomas, Sean Harrison, RosieJ. Lennon, Vanessa Tan, Cath Borwick, Pauline Emmett, Mona Jeffreys, Kate Northstone,
Giota Mitrou, Martin Wiseman, Rachel Thompson and Richard M. Martin. Cancer Epidemiol Biomarkers Prev November 1 2017.
Note to Editors:
A related article in the same journal presents two research teams independently applying the framework to investigate mechanisms between body fatness and breast cancer: A Comparative Study on the WCRF International/University of Bristol Methodology for Systematic Reviews of Mechanisms Underpinning Exposure–Cancer Associations. Gökhan Ertaylan et al.Cancer Epidemiol Biomarkers Prev November 1 2017 (26) (11) 1583-1594; DOI: 10.1158/1055-9965.EPI-17-0230
Along with Sarah Lewis, PhD, Richard Martin, PhD, Professor of Clinical Epidemiology, University of Bristol, was joint Principal Investigator on the paper.
-AICR/WCRF. Diet, Nutrition, Physical Activity and Prostate Cancer. 2014. https://www.aicr.org/continuous-update-project/prostate-cancer.html