Karina Dalsgaard Sørensen

Appraising causal relationships of dietary, nutritional and physical-activity exposures with overall and aggressive prostate cancer: two-sample Mendelian-randomization study based on 79 148 prostate-cancer cases and 61 106 controls

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DOI

  • Nabila Kazmi, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. S.J.Lewis@bristol.ac.uk.
  • ,
  • Philip Haycock, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. S.J.Lewis@bristol.ac.uk.
  • ,
  • Konstantinos Tsilidis, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK; MRC-PHE Centre for Environment, School of Public Health, Imperial College London, London, UK; Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece.
  • ,
  • Brigid M Lynch, Physical-Activity Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia.
  • ,
  • Therese Truong, INSERM, Center for Research in Epidemiology and Population Health (CESP), Cancer and Environment Team, Université Paris-Sud, Université Paris-Saclay, Villejuif, France.
  • ,
  • Richard M Martin, National Institute for Health Research (NIHR) Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and the University of Bristol, Bristol, UK.
  • ,
  • Sarah J Lewis, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. S.J.Lewis@bristol.ac.uk.
  • ,
  • PRACTICAL Consortium, CRUK, BPC3, CAPS, PEGASUS

BACKGROUND: Prostate cancer is the second most common male cancer worldwide, but there is substantial geographical variation, suggesting a potential role for modifiable risk factors in prostate carcinogenesis.

METHODS: We identified previously reported prostate cancer risk factors from the World Cancer Research Fund (WCRF)'s systematic appraisal of the global evidence (2018). We assessed whether each identified risk factor was causally associated with risk of overall (79 148 cases and 61 106 controls) or aggressive (15 167 cases and 58 308 controls) prostate cancer using Mendelian randomization (MR) based on genome-wide association-study summary statistics from the PRACTICAL and GAME-ON/ELLIPSE consortia. We assessed evidence for replication in UK Biobank (7844 prostate-cancer cases and 204 001 controls).

RESULTS: WCRF identified 57 potential risk factors, of which 22 could be instrumented for MR analyses using single nucleotide polymorphisms. For overall prostate cancer, we identified evidence compatible with causality for the following risk factors (odds ratio [OR] per standard deviation increase; 95% confidence interval): accelerometer-measured physical activity, OR = 0.49 (0.33-0.72; P = 0.0003); serum iron, OR = 0.92 (0.86-0.98; P = 0.007); body mass index (BMI), OR = 0.90 (0.84-0.97; P = 0.003); and monounsaturated fat, OR = 1.11 (1.02-1.20; P = 0.02). Findings in our replication analyses in UK Biobank were compatible with our main analyses (albeit with wide confidence intervals). In MR analysis, height was positively associated with aggressive-prostate-cancer risk: OR = 1.07 (1.01-1.15; P = 0.03).

CONCLUSIONS: The results for physical activity, serum iron, BMI, monounsaturated fat and height are compatible with causality for prostate cancer. The results suggest that interventions aimed at increasing physical activity may reduce prostate-cancer risk, although interventions to change other risk factors may have negative consequences on other diseases.

Original languageEnglish
JournalInternational Journal of Epidemiology
Volume49
Issue2
Pages (from-to)587-596
Number of pages10
ISSN0300-5771
DOIs
Publication statusPublished - Apr 2020

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