Sarah Lewis obtained a BSc in Genetics at the University of Sheffield in 1995 and then went on to complete a PhD in Genetic Epidemiology at the University of Manchester in 1999. She then had a series of short postdoctoral positions including a post at the International Agency for Research on Cancer. She joined the School of Social and Community Medicine in January 2004 as a Lecturer in genetic epidemiology and was promoted to Senior Lecturer in 2009. Her research interests are in using Mendelian randomization to understand risk factors for cancer and also to identify key nutrients required for in utero development. She is involved in a large UK-wide cohort study of cleft lip and palate, and a large birth cohort in which she is looking at the role of nutrition during pregnancy on childhood IQ and behaviour. She co-leads a work package on Mendelian randomization for the Intergrative Cancer epidemiology Programme which is funded by Cancer Research UK. She is a Principal Investigator on a project to develop a framework for systematic reviews of mechanistic studies of diet and cancer in collaboration with the World Cancer Research Fund. She also holds a grant from the WCRF to apply the above framework and Mendelian randomization to understanding the role of diet in prostate cancer.
Background: Many laboratory experiments are performed to identify causal pathways and in doing so inform human health. These mechanistic studies complement epidemiological findings and can offer insights into biological plausibility and pathways between exposure and disease. Systematic reviews are the most robust way to synthesise data which have addressed a common question. Methods for conducting and reporting rigorous systematic reviews of epidemiological studies are well established. However, such methods are lacking for mechanistic studies. We were commissioned by the WCRF to develop a protocol for conducting systematic reviews of mechanistic studies which underpin epidemiological associations between exposures and cancer.
Methods: A multidisciplinary team with expertise in informatics, statistics, epidemiology, systematic reviews, cancer biology and nutrition was assembled and a series of 5 one-day workshops took place involving presentations, group work and discussions, along with smaller meetings and research being carried out in the intervening periods.
Results: We have developed a template for carrying out rigorous systematic reviews of mechanistic studies, which includes guidance on; a two stage search strategy, (the first stage of which is a mechanisms discovery search, followed by a targeted search for studies on a specific mechanism), formulating a research question, applying inclusion/exclusion criteria, assessing the relevance of retrieved studies to the research question, assessing the quality of individual studies (using appropriate risk of bias tools), synthesizing the data from individual studies, assessing the strength of the overall body of evidence from human and animal studies separately and integrating the human and animal studies to reach a conclusion
Conclusion: The above template will be available to researchers in the future who wish to conduct robust systematic reviews of the mechanisms which underpin associations between exposures and cancer.
Funding: World Cancer Research Fund (WCRF)