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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

Research output: Contribution to journalArticle

  • the PRACTICAL Consortium
Original languageEnglish
Article numberdyz235
Number of pages10
JournalInternational Journal of Epidemiology
DOIs
DateAccepted/In press - 5 Nov 2019
DatePublished (current) - 5 Dec 2019

Abstract

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’s (WCRF) 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 (GWAS) summary statistics from the PRACTICAL and GAME-ON/ELLIPSE consortia. We assessed evidence for replication in UK Biobank (7,844 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 (SNPs). 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 mono-unsaturated 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, mono-unsaturated 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.

    Structured keywords

  • ICEP

    Research areas

  • Mendelian randomization, prostate cancer, physical activity

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  • Full-text PDF (accepted author manuscript)

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Oxford University Press at https://academic.oup.com/ije/advance-article/doi/10.1093/ije/dyz235/5650986?searchresult=1. Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 457 KB, PDF document

    Embargo ends: 5/12/20

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