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Applying Mendelian randomization to appraise causality in relationships between nutrition and cancer.
Wade, Kaitlin H; Yarmolinsky, James; Giovannucci, Edward; Lewis, Sarah J; Millwood, Iona Y; Munafò, Marcus R; Meddens, Fleur; Burrows, Kimberley; Bell, Joshua A; Davies, Neil M; Mariosa, Daniela; Kanerva, Noora; Vincent, Emma E; Smith-Byrne, Karl; Guida, Florence; Gunter, Marc J; Sanderson, Eleanor; Dudbridge, Frank; Burgess, Stephen; Cornelis, Marilyn C; Richardson, Tom G; Borges, Maria Carolina; Bowden, Jack; Hemani, Gibran; Cho, Yoonsu; Spiller, Wes; Richmond, Rebecca C; Carter, Alice R; Langdon, Ryan; Lawlor, Deborah A; Walters, Robin G; Vimaleswaran, Karani Santhanakrishnan; Anderson, Annie; Sandu, Meda R; Tilling, Kate; Davey Smith, George; Martin, Richard M; Relton, Caroline L.
Afiliación
  • Wade KH; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. kaitlin.wade@bristol.ac.uk.
  • Yarmolinsky J; Medical Research Council (MRC) Integrative Epidemiology Unit (IEU) at the University of Bristol, Bristol, UK. kaitlin.wade@bristol.ac.uk.
  • Giovannucci E; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
  • Lewis SJ; Medical Research Council (MRC) Integrative Epidemiology Unit (IEU) at the University of Bristol, Bristol, UK.
  • Millwood IY; Departments of Nutrition and Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, USA.
  • Munafò MR; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
  • Meddens F; Medical Research Council (MRC) Integrative Epidemiology Unit (IEU) at the University of Bristol, Bristol, UK.
  • Burrows K; Bristol National Institute for Health Research (NIHR) Biomedical Research Centre, Bristol, UK.
  • Bell JA; Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU) and the Medical Research Council Population Health Research Unit (MRC PHRU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • Davies NM; Medical Research Council (MRC) Integrative Epidemiology Unit (IEU) at the University of Bristol, Bristol, UK.
  • Mariosa D; Bristol National Institute for Health Research (NIHR) Biomedical Research Centre, Bristol, UK.
  • Kanerva N; School of Psychological Science, University of Bristol, Bristol, UK.
  • Vincent EE; Department of Economics, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
  • Smith-Byrne K; Department of Applied Economics, Erasmus School of Economics, Erasmus University Rotterdam, Rotterdam, The Netherlands.
  • Guida F; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
  • Gunter MJ; Medical Research Council (MRC) Integrative Epidemiology Unit (IEU) at the University of Bristol, Bristol, UK.
  • Sanderson E; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
  • Dudbridge F; Medical Research Council (MRC) Integrative Epidemiology Unit (IEU) at the University of Bristol, Bristol, UK.
  • Burgess S; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
  • Cornelis MC; Medical Research Council (MRC) Integrative Epidemiology Unit (IEU) at the University of Bristol, Bristol, UK.
  • Richardson TG; K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
  • Borges MC; International Agency for Research On Cancer (IARC), Lyon, France.
  • Bowden J; Nightingale Health Oy, Helsinki, Finland.
  • Hemani G; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
  • Cho Y; Medical Research Council (MRC) Integrative Epidemiology Unit (IEU) at the University of Bristol, Bristol, UK.
  • Spiller W; Cellular and Molecular Medicine, Faculty of Life Sciences, University of Bristol, Bristol, UK.
  • Richmond RC; International Agency for Research On Cancer (IARC), Lyon, France.
  • Carter AR; International Agency for Research On Cancer (IARC), Lyon, France.
  • Langdon R; International Agency for Research On Cancer (IARC), Lyon, France.
  • Lawlor DA; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
  • Walters RG; Medical Research Council (MRC) Integrative Epidemiology Unit (IEU) at the University of Bristol, Bristol, UK.
  • Vimaleswaran KS; Department of Health Sciences, University of Leicester, Leicester, UK.
  • Anderson A; MRC Biostatistics Unit, University of Cambridge, Cambridge, UK.
  • Sandu MR; Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • Tilling K; Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
  • Davey Smith G; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
  • Martin RM; Medical Research Council (MRC) Integrative Epidemiology Unit (IEU) at the University of Bristol, Bristol, UK.
  • Relton CL; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Cancer Causes Control ; 33(5): 631-652, 2022 May.
Article en En | MEDLINE | ID: mdl-35274198
Dietary factors are assumed to play an important role in cancer risk, apparent in consensus recommendations for cancer prevention that promote nutritional changes. However, the evidence in this field has been generated predominantly through observational studies, which may result in biased effect estimates because of confounding, exposure misclassification, and reverse causality. With major geographical differences and rapid changes in cancer incidence over time, it is crucial to establish which of the observational associations reflect causality and to identify novel risk factors as these may be modified to prevent the onset of cancer and reduce its progression. Mendelian randomization (MR) uses the special properties of germline genetic variation to strengthen causal inference regarding potentially modifiable exposures and disease risk. MR can be implemented through instrumental variable (IV) analysis and, when robustly performed, is generally less prone to confounding, reverse causation and measurement error than conventional observational methods and has different sources of bias (discussed in detail below). It is increasingly used to facilitate causal inference in epidemiology and provides an opportunity to explore the effects of nutritional exposures on cancer incidence and progression in a cost-effective and timely manner. Here, we introduce the concept of MR and discuss its current application in understanding the impact of nutritional factors (e.g., any measure of diet and nutritional intake, circulating biomarkers, patterns, preference or behaviour) on cancer aetiology and, thus, opportunities for MR to contribute to the development of nutritional recommendations and policies for cancer prevention. We provide applied examples of MR studies examining the role of nutritional factors in cancer to illustrate how this method can be used to help prioritise or deprioritise the evaluation of specific nutritional factors as intervention targets in randomised controlled trials. We describe possible biases when using MR, and methodological developments aimed at investigating and potentially overcoming these biases when present. Lastly, we consider the use of MR in identifying causally relevant nutritional risk factors for various cancers in different regions across the world, given notable geographical differences in some cancers. We also discuss how MR results could be translated into further research and policy. We conclude that findings from MR studies, which corroborate those from other well-conducted studies with different and orthogonal biases, are poised to substantially improve our understanding of nutritional influences on cancer. For such corroboration, there is a requirement for an interdisciplinary and collaborative approach to investigate risk factors for cancer incidence and progression.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Análisis de la Aleatorización Mendeliana / Neoplasias Tipo de estudio: Clinical_trials / Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Cancer Causes Control Asunto de la revista: EPIDEMIOLOGIA / NEOPLASIAS Año: 2022 Tipo del documento: Article Pais de publicación: Países Bajos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Análisis de la Aleatorización Mendeliana / Neoplasias Tipo de estudio: Clinical_trials / Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Cancer Causes Control Asunto de la revista: EPIDEMIOLOGIA / NEOPLASIAS Año: 2022 Tipo del documento: Article Pais de publicación: Países Bajos