In 2007, Hsing et al. summarized five studies on MetS and prostate cancer risk and concluded that the epidemiologic evidence was insufficient to suggest a link between MetS and PCa [37
]. In 2012, Esposito et al. performed a systematical review and meta-analysis on the association of MetS and cancer risk including prostate cancer. The authors also concluded that MetS was not associated with prostate cancer risk too [22
]. In the present study, we updated the data and used the current evidence to analyze whether MetS is associated with prostate cancer risk. We observed the same result as previous meta-analysis; no association could be detected between Mets and prostate cancer.
We believe the result is reliable for two reasons. Firstly, only longitudinal cohort studies were included in this analysis, imparting strong evidence for our conclusions. In addition, the association between MetS and prostate cancer may be affected by several factors, including heterogeneity among the individual studies. The heterogeneity may arise from differences in age, race, the definition of MetS [22
], and geographic factors [26
]. Further, MetS is a syndrome composed of at least 3 components, and the individual component may exert antagonistic functions on one another Thus the syndrome may represent an integrated outcome that combines neutralizing positive and negative functions. For example, a meta-analysis revealed that diabetes mellitus was significantly negatively associated with prostate cancer risk in population-based studies (RR
0.72, 95% CI: 0.64-0.81) and cohort studies conducted in the USA (RR
0.79, 95% CI: 0.73, 0.86) [38
]. Furthermore, several genome-wide association studies suggest that diabetes mellitus and prostate cancer share certain genetic factors, including the HNF1β
genes, and a previous study suggested that JAZF1
might represent a potential target against diabetes and obesity [39
]. Although hypertension was found to be positively associated with prostate cancer risk [33
], Obesity is negatively with localized prostate cancer (0.94, 95% CI, 0.91-0.97) and positively associated with advanced prostate cancer risk (1.07, 95% CI 1.01-1.13) [43
However, after analyses of several parameters of PCa aggressiveness and progression, we found MetS to be significantly associated with an increased risk of prostate cancer with a high-Gleason score or advanced clinical stage, with biochemical recurrence after primary treatment and with prostate cancer-specific mortality. If confirmed by more investigations, this finding may open a new research field on PCa development and progression, potentially leading to new strategies or methods for PCa treatment. MetS is a major public health problem and prostate cancer is the most prevalent solid organ tumor, accounts for 29% of all cancer cases and the second most common cause of death by cancer among men in the USA [44
]. Therefore we believe that there is a compelling need to investigate this association between MetS and prostate cancer although the association is not strong.
Nevertheless, the reliability of these results is limited. First, Gleason score and clinical stage data were extracted from cross-sectional studies not longitudinal cohort studies. Second, there exists a small difference among studies on the definition of high-grade Gleason PCa, some authors defined a high Gleason score
7 whereas others defined a high score as >7. Third, the pathological stage data in some studies were from biopsy not radical prostatectomy specimens. Last but not least, to date there remains limited studies focusing on this association, although many of the available studies are well designed case-control or longitudinal cohort studies.
In addition to the limitations listed above, another limitation for the analyses of the association between MetS and prostate cancer risk or prostate cancer parameters is that we did not perform a meta-regression to attempt to explain the heterogeneity of the study because of the varying adjustments in the individual studies. The result of a recent meta-analysis on 9 cross-sectional studies of metabolic syndrome in adult cancer survivors increases the weight of this suspicion, as it revealed that no significant association was found for non-hematologic malignancies, including testicular tumor, prostate cancer, sarcoma, and epithelial ovarian [45
]. Therefore, there is an urgent future need to confirm this association and to find potential mechanisms to explain how metabolic factors affect the development or progression of PCa.