Low circulating total adiponectin, especially its non-high-molecular weight fraction, represents a promising risk factor for colorectal cancer: a meta-analysis

Aim: The principal goal of this meta-analysis is to test the hypothesis that circulating total adiponectin or certain fractions may represent a promising biological candidate in modulating the risk of colorectal cancer. Methods: The processes of paper identification, paper selection and data extraction were accomplished independently by two authors. Effect-size estimates were expressed as weighted mean difference (WMD) and 95% confidence interval (95% CI). A total of 31 papers including 48 qualified studies (7,554 patients with colorectal cancer and 9,798 controls) were meta-analyzed. Results: Pooling all studies found that circulating total adiponectin was significantly lower in patients with colorectal cancer than in controls (WMD: -0.76 mu g/mL, 95% CI: -1.20 to -0.32, p=0.001), with significant heterogeneity (I-2: 94.2%) and low publication bias (Egger's p=0.336). By adiponectin fractions, the difference in high-molecular weight (HMW) adiponectin was comparable between the two groups (WMD: -0.22 mu g/mL, 95% CI: -0.70 to 0.25, p=0.350), while non-HMW adiponectin was significantly lower in patients with colorectal cancer than in controls (WMD: -0.27 mu g/mL, 95% CI: -0.35 to -0.19, p<0.001), with marginal heterogeneity (I-2: 52.3%). Subgroup analysis revealed that effect-size estimates were heterogeneous when grouping studies by cancer subtype, region, study design, matching status, gender and obesity. Further meta-regression analysis indicated that age and gender were significant potential sources of heterogeneity. The results showed the studied subgroups were not subject to publication bias (Egger's p<0.1). Conclusion: Our data collectively indicate that low circulating total adiponectin, especially its non-HMW fraction, represents a promising risk factor for colorectal cancer. Further studies are needed to explore underlying mechanisms.