We also manually searched relevant journals, bibliographies, and reviews for additional articles. The search had no language restriction. Inclusion criteria The eligibility of each ATM/ATR inhibitor study was assessed independently by two investigators (YX and HX). We included only cohort studies of MetS and prostate cancer risk or prostate cancer-specific mortality and clinical studies of MetS and Gleason score or clinical stage at diagnosis or biochemical recurrence after treatment. We included studies that reported
standardized forms of relative risk, risk ratio, hazard ratio or odds ratio with estimates of confidence intervals (CIs) or with sufficient data to estimate CIs. We used relative risks (RRs) to represent various effect estimates in a cohort study in this meta-analysis. Exclusion criteria We excluded reviews, editorials, meta-analysis and animal studies. Among the 23 studies that underwent full-text reviews, we excluded a study on MetS and prostate cancer risk of re-biopsy , a study that did not use a standard definition of MetS [32, 33] and BIIB057 nmr one case-control study on MetS and prostate cancer risk . For studies previously published on the same database [34, 35], we included only the most recent findings [19, 20]. All of the studies on which we focused reported RRs with 95% CIs or sufficient data to estimate
them. Data extraction The data extracted included KU-57788 in vitro publication data (the first author’s last name, year of publication, and country of the population studied), study design, population resources, number of cases, risk estimates with their corresponding CIs, and variables controlled for by matching or in the most adjusted model. Abstractions of the data elements were conducted separately by two authors; discordant results were resolved by check details consensus. Statistical analysis Firstly, we updated the data and attempted to analyze the association of MetS
with the prostate cancer risk in longitudinal cohort studies only. Subsequently, we assessed the association between MetS and prostate cancer-specific mortaligy in cohort studies and between MetS and high grade Gleason PCa and/or advanced PCa or biochemical recurrence in clinical studies. We pooled all of the RRs for MetS and assessed the heterogeneity between the studies by Q and I2 statistics, which are distributed as x2 statistics . A value of P < 0.10 was used to indicate lack of homogeneity (heterogeneity) among effects. We used a fixed-effects model if I2 value significance was <0.1; otherwise, we used a random-effect model. Sensitivity analysis was conducted by omitting one study at a time, generating the pooled estimates and comparing with the original estimates. Funnel plots and both Begg’s and Egger’s tests were used to evaluate publication bias. All analyses were performed using STATA version 9.0 statistical software (Stata, College Station, Texas, USA).