Metabolic syndrome biomarkers and prostate cancer risk in the UK Biobank

Abstract

We investigated the association between metabolic syndrome (MetS) and its components and risk of prostate cancer (PCa) in a cohort of men enrolled in the UK Biobank. Our study cohort included 220 622 PCa-free men with baseline measurements of triglycerides (TGs), HDL-cholesterol (HDL), glycated hemoglobin (HbA1c), blood pressure (BP), and waist circumference (WC). Multivariable Cox proportional hazards regression was used to analyze associations with PCa for: individual metabolic components (TG, HDL, HbA1c, BP, WC), combinations of two and three components, and MetS overall (three or more components). We conducted mediation analyses to examine potential hormonal and inflammatory pathways (total testosterone [TT], Creactive protein [CRP], insulin-like growth factor 1 [IGF-1]) through which MetS components may influence PCa risk. A total of 5409 men in the study developed PCa during a median follow-up of 6.9 years. We found no significant association between MetS and PCa risk (hazard ratio [HR] = 0.99, 95% confidence interval [CI] = 0.92-1.06). No associations were found with PCa risk and individual measurements of TG, HDL, BP, or WC. However, an inverse association was observed with elevated HbA1c (≥42 mmol/mol) (HR = 0.89, 95% CI = 0.79-0.98). Consistent inverse associations were observed between HbA1c and risk of PCa. Mediation analysis revealed TT, CRP, and IGF-1 as potential mediating factors for this association contributing 10.2%, 7.1%, and 7.9% to the total effect, respectively. Overall MetS had no association with PCa risk. However, a consistent inverse association with PCa risk was found for HbA1c. This association may be explained in part through hormonal and inflammatory pathways.

Personalized 5-Year Prostate Cancer Risk Prediction Model in Korea Based on Nationwide Representative Data

“…Higher BMI was associated with increased risk of PC, which is consistent with a previous Korean prediction model [15] and other epidemiological studies [46,47]. As found in previous studies, persons with hypertension showed a higher risk of PC [28], and DM was inversely associated with PC incidence [26,27].…”

“…Among potential risk factors for PC, we selected seven candidates for prediction of PC risk according to a literature review. These were: age; cigarette smoking [22]; alcohol consumption [23,24]; and the metabolic components of body mass index (BMI), regular physical exercise, and presence of DM and hypertension [25][26][27][28].…”

Development of diabetes mellitus following hormone therapy in prostate cancer patients is associated with early progression to castration resistance

“…Previous clinical studies on the relationship between lifestyle-related metabolic disorders, particularly DM, and PC appear controversial [4][5][6][7] . A retrospective clinical report has shown the association of CRPC progression with DM in a subset of PC patients who had no radiographic evidence of metastasis, but not in all PC patients.…”

“…Recent studies imply that 8-12% of PC cases involve a hereditary component associated with germline mutations or alterations in genes, such as BRCA1, BRCA2, HOXB13 or DNA MMR genes 3 . On the other hand, presumed acquired risk factors contributing to the development or poor prognosis of PC appear to include lifestyle-related diseases, such as hypertension (HT) and type 2 diabetes mellitus (DM) independent of obesity or serum triglycerides 4,5 , whereas plenty of conflicting evidence has been reported 6,7 . Initial treatment options for PC after cancer staging and grading include prostatectomy, radiation therapy, and hormone therapy, especially androgen deprivation therapy (ADT) 8 .…”

Advanced and Innovative Nano-Systems for Anticancer Targeted Drug Delivery

“…ApoA-I can specifically target SR-BI and mediate the anti-inflammatory ability of macrophages by regulating the production of cytokines in macrophages [ 76 ]. Therefore, SR-BI can be used as a specific target for the treatment of common tumors such as breast cancer, ovarian cancer and prostate cancer [ 77 , 78 ] ( Figure 3 B). Hence, rHDL can be regarded as an outstanding encapsulated carrier to deliver various drugs with the following unique advantages ( Figure 3 C).…”