Circulating adipokines and risk of obesity related cancers: A systematic review and meta-analysis

Background: Obesity can influence on carcinogenesis through alterations in adipokines and subsequent inflammatory changes. This meta-analysis was aimed to comprehensively assess the association between circulating adipokines and risk of obesity-related cancers. Methods: Pubmed and Embase were searched up to October 2017 for observational studies investigating the relationship between adipokines and cancers. Pooled odds ratio and the corresponding 95% confidence interval was estimated through the meta-analysis using a random-effects model. Findings A total of 93 observational studies (adiponectin = 60, high molecular weight adiponectin = 9, leptin = 39, IL-6 = 16, TNF-α = 10, and resistin = 17) were included. Adiponectin was significantly associated with decreased risk of cancer (pooled OR 0.70, 95% CI 0.60–0.80; I² = 71.9%; P_{heterogeneity} <0.01). Leptin was significantly associated with increased risk of cancer (1.26, 1.05–1.51; I² = 65.7%; P_{heterogeneity} <0.01). For each 5 μg/ml increase in adiponectin and 5 ng/ml increase in leptin, the pooled OR was 0.88 (0.83–0.93; I² = 80.2%; P_{heterogeneity} <0.01) and 1.05 (1.01–1.09; I² = 67.9%; P_{heterogeneity}<0.01)), respectively. There was nonlinear dose-response association (P_nonlinearity for adiponectin = 0.01; P_nonlinearity for leptin = 0.003).IL-6 (1.09, 0.94–1.25), TNF- α (1.65, 0.99–2.74), and resistin (1.28, 0.78–2.11) was not associated with risk of cancer. By cancer site and type, highest category of adiponectin was associated with decreased risk of breast (OR 0.74, 0.60-0.91), colorectal (0.74, 0.60–0.91), and endometrial cancer (0.49, 0.34–0.72). Higher leptin was associated with increased risk of endometrial (1.88, 1.24–2.87) and kidney cancer (2.07, 1.51–2.83). Conclusion: Our study suggests that adiponectin and leptin may play a role in the etiology of cancer.