The relationship between metabolic syndrome components and prostate cancer risk : a Mendelian randomization study

Purpose Numerous epidemiological studies have explored the association between the components of metabolic syndrome (MetS) and risk of prostate cancer (PCa). However, to date, the findings have yielded inconclusive results. This study aimed to evaluate the causal effects of MetS components, including obesity, disturbances in glucose metabolism, and hypertension, on the development of PCa. Methods Data for type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), obesity, body mass index (BMI), waist circumference, hypertension, and PCa were acquired from genome-wide association studies in FinnGen, UK Biobank, and the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome consortium. We used two-sample univariate and multivariate Mendelian randomization (MR) to estimate the causal relationships between MetS components and PCa risk. Sensitivity analyses were employed to assess the violation of the MR assumptions. Results No evidence of an association between genetically predicted concentrations of T1DM, T2DM, hypertension, obesity, and BMI and PCa risk was found in our study. Waist circumference concentration was negatively associated with PCa risk in the univariate analysis; however, this association disappeared after adjustment for BMI. Genetic variants associated with waist circumference were found to be correlated with decreased PCa risk when BMI was reintroduced into the univariate MR analysis. Conclusion We observed that among the MetS components, genetically predicted waist circumference was associated with decreased PCa risk, whereas no association was observed between BMI and PCa risk. This may be related to the distribution characteristics of fat throughout the body and warrants further investigation.