The association between metabolic syndrome and the risk of prostate cancer, high-grade prostate cancer, advanced prostate cancer, prostate cancer-specific mortality and biochemical recurrence

Abstract

BackgroundAlthough a previous meta-analysis reported no association between metabolic syndrome (MetS) and prostate cancer risk, a number of studies suggest that MetS may be associated with the aggressiveness and progression of prostate cancer. However, these results have been inconsistent. This systematic review and meta-analysis investigated the nature of this association.MethodsWe systematically searched MEDLINE, EMBASE and bibliographies of retrieved studies up to January 2013 using the keywords “metabolic syndrome” and “prostate cancer”. We assessed relative risks (RRs) of the prostate cancer, several parameters of prostate cancer aggressiveness and progression associated with MetS using 95% confidence intervals (95% CIs).ResultsThe literature search produced 547 hits from which 19 papers were extracted for the meta-analysis. In cancer-free population with and without MetS, the combined adjusted RR (95% CI) of prostate cancer risk and prostate cancer-specific mortality in longitudinal cohort studies is 0.96 (0.85 ~ 1.09) and 1.12 (1.02 ~ 1.23) respectively. In the prostate cancer patients with and without MetS, the combined unadjusted OR (95% CI) of high grade Gleason prostate cancer is 1.44 (1.20 ~ 1.72), the OR of advanced prostate cancer is 1.37 (1.12 ~ 1.68) and the OR of biochemical recurrence is 2.06 (1.43 ~ 2.96).ConclusionsThe overall analyses revealed no association between MetS and prostate cancer risk, although men with MetS appear more likely to have high-grade prostate cancer and more advanced disease, were at greater risk of progression after radical prostatectomy and were more likely to suffer prostate cancer-specific death. Further primary studies with adjustment for appropriate confounders and larger, prospective, multicenter investigations are required.

The Role of the IGF Axis in Epithelial-to-Mesenchymal Transition during the Progression of Prostate Cancer

“…A metaanalysis on the association between diabetes and PCa showed that diabetic patients had a reduced risk of developing PCa [18]. However, despite the risk of developing PCa being reduced by diabetes, [19] men having both prostate cancer and diabetes, suffered more aggressive tumours, a higher risk of cancer recurrence and worse overall survival [20] which suggests metabolic exposures affect progression but not initiation, consistent with the epidemiology observations of geographical variations.…”

“…A metaanalysis on the association between diabetes and PCa showed that diabetic patients had a reduced risk of developing PCa [18]. However, despite the risk of developing PCa being reduced by diabetes, [19] men having both prostate cancer and diabetes, suffered more aggressive tumours, a higher risk of cancer recurrence and worse overall survival [20] which suggests metabolic exposures affect progression but not initiation, consistent with the epidemiology observations of geographical variations.The crucial underlying molecular mechanism that promotes the progression of localised prostate cancer to become metastatic and castration resistant remains largely elusive. Contributing mechanisms have been suggested for development of metastatic androgenindependent prostate cancer including androgen receptor (AR) over-expression, AR splice variants such as AR3/AR-V7 and AR4/AR-V1, and mutations in the ligand binding domain of the AR as well as cross-talk with other growth factor signalling pathways particularly the insulin-like growth factor (IGF) axis [21].…”

Metabesity and urological cancers

“…Some authors reported that metabolic syndrome did not promote the development of prostate cancer. [28,29] In an Australian study, it was found that increases in waist circumference, and triglyceride levels decreased the risk of development of prostate cancer. [13] In a more recent study, decrease in the development of prostate cancer in the presence of overweightness or obesity and diabetes mellitus has been indicated.…”

Metabolic Syndrome in Prostate Cancer: Impact on Risk and Outcomes

“…In a systematic review and meta-analysis of seven studies, Xiang et al [25] found that metabolic syndrome was associated with a 36% increase in odds ratio (OR) of a Gleason score of ≥7 (OR: 1.36; 95% CI: 0.90-2.06) and a 37% increased risk of advanced clinical stage (≥T3; OR: 1.37; 95% CI: 1.12-1.68; n = 4 studies). In three studies analyzed, metabolic syndrome was associated with a higher risk of prostate cancerspecific death (RR: 1.12; 95% CI: 1.02-1.…”