The study evaluated 22 potential risk factors from the 2018 World Cancer Research Fund (WCRF) Continuous Update Project (CUP), which is a systematic collection of the global literature on diet, weight, and physical activity and prostate cancer.1 Of these risk factors, the MR analysis found only 4 risk factors to be significantly associated with the risk of developing prostate cancer, including 2 related to diet, 1 related to physical activity, and 1 linked to body mass index (BMI).

Higher serum iron levels were modestly associated with a lower likelihood of developing prostate cancer (odds ration [OR] per standard deviation increase, 0.92; 95% CI, 0.86-0.98; P =.007). In contrast, monounsaturated fat intake (as measured by questionnaire) was associated with a modest increase in the odds of prostate cancer (OR, 1.07; 95% CI, 1.01-1.15; P =.03). However, the authors noted that other studies have shown that there is poor association between self-reported monounsaturated fat intake amounts (obtained by questionnaire) and actual levels of monounsaturated fat intake that measured from blood.

Engagement in physical activity, measured as average acceleration by an accelerometer, was associated with a 51% decrease in the risk of developing prostate cancer (OR, 0.49; 95% CI, 0.33-0.72; P =.0003). Average acceleration could be high with light-intensity exercise, such as walking. The authors indicated that the mechanism underlying this association is not clear, but may be due to improved insulin sensitivity, reduced growth factors and/or hormones, and changes in the antioxidant defense system or immune system.

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A higher BMI was also associated with a decreased risk of prostate cancer (OR, 0.90; 95% CI, 0.84-0.97; P =.003). However, there was no association between waist circumference/waist-to-hip ratio and risk for prostate cancer. The authors suggested that this association could be due to increased production of estrogen, and therefore, decreased exposure to testosterone. Prostate cancer is known to be stimulated by androgens such as testosterone.

The MR analysis also evaluated the 22 potential risk factors associated with aggressive prostate cancer. Only greater height was significantly associated with the risk of developing aggressive prostate cancer (OR, 1.07; 95% CI, 1.01-1.15; P =.003), which was consistent with findings from observational studies. The authors speculated that this association may be a result of the hormonal microenvironment within the prostate due to health and nutrition status during growth.


The authors of the study suggested that the lifestyle interventions that increase physical activity may reduce the risk of developing prostate cancer. However, they caution against adopting interventions that seek to increase serum iron levels, decrease monounsaturated fat, or increase BMI, because these changes may have a negative effect on other aspects of health. The authors also noted that the results for accelerator-monitored physical activity and monounsaturated fat were not consistent with findings from observational studies.


  1. Kazmi N, Haycock P, Tsilidis K, et al. 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 [published online December 5, 2019]. Int J Epidemiol. doi: 10.1093/ije/dyz235
  2. Sekula P, Del Greco MF, Pattaro C, Köttgen A. Mendelian randomization as an approach to assess causality using observational data. J Am Soc Nephrol. 2016;27(11):3253-3265.
  3. Emdin CA, Khera AV, Kathiresan S. Mendelian randomization. JAMA. 2017;318(19):1925-1926.