Circulating adiponectin and leptin and risk of overall and aggressive prostate cancer: a systematic review and meta-analysis

Abstract

Obesity is associated with an increased risk of advanced, recurrent and fatal prostate cancer. Adipokines may mediate this relationship. We conducted a systematic review and meta-analysis of associations of leptin and adiponectin with overall and aggressive prostate cancer. Bibliographic databases were systematically searched up to 1st April 2017. Log Odds Ratios (ORs) per 2.5 unit increase in adiponectin or leptin levels were derived and pooled. All analyses were stratified by study type (cross-sectional/prospective). 746 papers were retrieved, 34 eligible studies identified, 31 of these could be included in the meta-analysis. Leptin was not consistently associated with overall prostate cancer (pooled OR 1.00, 95%CI 0.98–1.02, per 2.5 ng/ml increase, prospective study OR 0.97, 95%CI 0.95–0.99, cross-sectional study OR 1.19, 95%CI 1.13–1.26) and there was weak evidence of a positive association with aggressive disease (OR 1.03, 95%CI 1.00–1.06). There was also weak evidence of a small inverse association of adiponectin with overall prostate cancer (OR 0.96, 95%CI 0.93–0.99, per 2.5 µg/ml increase), but less evidence of an association with aggressive disease (OR 0.98, 95%CI 0.94–1.01). The magnitude of any effects are small, therefore levels of circulating adiponectin or leptin alone are unlikely to be useful biomarkers of risk or prognosis.

Metabolic syndrome, obesity and cancer risk

“…It has been supposed that adipokines, such as leptin and adiponectin, may be the molecular mechanism behind the link between obesity and prostate cancer progression. However, Leptin was not associated with an increased risk of prostate cancer (odds ratio [OR] = 1.00) whereas evidence of a positive association with aggressive disease was observed (OR = 1.03) [14 ▪▪ ]. On the other hand, adiponectin resulted in a protective factor of overall prostate cancer risk (OR = 0.96) and aggressive disease (OR = 0.98) [14 ▪▪ ].…”

“…However, Leptin was not associated with an increased risk of prostate cancer (odds ratio [OR] = 1.00) whereas evidence of a positive association with aggressive disease was observed (OR = 1.03) [14 ▪▪ ]. On the other hand, adiponectin resulted in a protective factor of overall prostate cancer risk (OR = 0.96) and aggressive disease (OR = 0.98) [14 ▪▪ ]. Besides adipokines, a major role in tumorigenesis is reserved for steroid hormones and insulin/insulin-like growth factor 1 (IGF1) pathways.…”

Thromboinflammatory Processes at the Nexus of Metabolic Dysfunction and Prostate Cancer: The Emerging Role of Periprostatic Adipose Tissue

“…Indeed, AT dysfunction, observed in conditions of chronic energy excess, MetS and obesity, further increases leptin production which in turn, due to its proinflammatory nature, augments cytokine production and T-cell proliferation, thereby amplifying AT inflammation [ 159 , 161 , 162 ]. Within the context of PCa, leptin was not consistently associated with overall PCa and there was weak evidence of a positive association between leptin and PCa aggressiveness [ 163 ]. Nevertheless, hyperleptinemia remains a preeminent feature of PCa and PCa tissues express higher levels of leptin and the leptin receptor in comparison to BPH and healthy prostates [ 164 ].…”

“…Although the available literature concerning the associations between serum adiponectin levels and the various facets of carcinogenesis is quite conflicting, the most accredited hypothesis is that adiponectin exerts a protective role against the development and progression of PCa [ 163 , 197 , 198 , 199 ]. A meta-analysis concluded that the concentration of adiponectin in PCa patients was significantly lower than in control subjects [ 200 ].…”

The Adipose Tissue at the Crosstalk Between EDCs and Cancer Development

“…Clinical studies indicated a positive correlation between leptin:adiponectin ratio and increased risks for some cancers like ECa in post-menopausal women ( 72 ), BCa ( 73 ) and PCa ( 74 ). However, a metanalysis has then discussed leptin:adiponectin ratio and demonstrated no strong prognosis value for PCa ( 75 ).…”