Cardiometabolic comorbidities and prostate cancer risk: evidence from the prostate, lung, colorectal, and ovarian cancer screening trial

Background This study aims to explore the association between cardiometabolic diseases (CMDs) involving diabetes and the risk of prostate cancer (PCa) as well as its mortality. Methods The population-based cohort, comprising 71, 566 participants, was derived from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. CMDs encompassed three conditions, namely diabetes, heart diseases, and stroke. Multivariable Cox proportional hazards and competing risk regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for assessing associations between individual diabetes, coexisting CMDs, and PCa incidence and mortality. Results At baseline, 12, 979 participants had at least one CMD, while 2, 391 had two or more concurrent CMDs. Over a 17-year mean follow-up, 8, 263 participants were diagnosed with PCa. Participants with baseline diabetes exhibited an 18% elevated risk of developing PCa compared with CMD-free counterparts (HR: 1.18, 95% CI: 1.08~1.29). Among participants with multimorbidity, only diabetes-heart disease comorbidity was significantly associated with an elevated risk of PCa incidence (HR: 1.31, 95% CI: 1.09~1.59). Neither diabetes, heart disease, nor stroke had a statistically significant association with PCa-specific mortality risk. However, compared with CMD-free individuals, those with a single type of CMD exhibited a significantly reduced risk of non-aggressive PCa-specific mortality (HR: 0.50, 95% CI: 0.26~0.99). Conclusions Baseline diabetes was independently associated with an increased incidence of PCa, and the comorbidity of diabetes with heart disease further amplified this risk. The presence of a single CMD reduced the risk of non-invasive PCa-specific mortality in affected individuals.