Risk factors for prostate cancer: An umbrella review of prospective observational studies and mendelian randomization analyses

Background: The incidence of prostate cancer is increasing in older males globally. Age, ethnicity, and family history are identified as the well-known risk factors for prostate cancer, but few modifiable factors have been firmly established. The objective of this study was to identify and evaluate various factors modifying the risk of prostate cancer reported in meta-analyses of prospective observational studies and mendelian randomization (MR) analyses. Methods and findings: We searched PubMed, Embase, and Web of Science from the inception to January 10, 2022, updated on September 9, 2023, to identify meta-analyses and MR studies on prostate cancer. Eligibility criteria for meta-analyses were (1) meta-analyses including prospective observational studies or studies that declared outcome-free at baseline; (2) evaluating the factors of any category associated with prostate cancer incidence; and (3) providing effect estimates for further data synthesis. Similar criteria were applied to MR studies. Meta-analysis was repeated using the random-effects inverse-variance model with DerSimonian—Laird method. Quality assessment was then conducted for included meta-analyses using AMSTAR-2 tool and for MR studies using STROBE-MR and assumption evaluation. Subsequent evidence grading criteria for significant associations in meta-analyses contained sample size, P values and 95% confidence intervals, 95% prediction intervals, heterogeneity, and publication bias, assigning 4 evidence grades (convincing, highly suggestive, suggestive, or weak). Significant associations in MR studies were graded as robust, probable, suggestive, or insufficient considering P values and concordance of effect directions. Conclusions: In this large-scale study, we summarized the associations of various factors with prostate cancer risk and provided comparisons between observational associations by meta-analysis and genetically estimated causality by MR analyses. In the absence of convincing overlapping evidence based on the existing literature, no robust associations were identified, but some effects were observed for height, physical activity, and smoking. Huijie Cui and team identify and evaluate various risk factors of prostate cancer reported in meta-analyses of prospective observational studies and Mendelian randomization analyses.Why was this study done?: What did the researchers do and find?: What do these findings mean?: