Abstract
INTRODUCTION: Metabolic syndrome (MetS) may be associated with obesity-related cancer (ORC) owing to shared risk factors like physical inactivity, insulin resistance, gut microbiome dysfunction, and inflammation. We conducted an umbrella review of systematic reviews with meta-analysis to synthesize the evidence on the association between MetS and ORC risk and survival. METHODS: Searches in five databases (Medline, Embase, CINAHL, Cochrane Library, and Scopus) retrieved 2524 systematic reviews with meta-analyses (SRMAs), which underwent title and abstract screening (2524), full-text review (41), and data extraction for included SRMAs (21). Summary effects and 95% confidence intervals were re-estimated using random-effects models. Methodological quality, certainty of evidence, and publication bias were assessed using the AMSTAR 2, modified Ioannidis criteria, and Egger's test, respectively. RESULTS: A total of 25 associations between MetS and ORC risk and five between MetS and survival were evaluated. Overall, 10 associations evaluating MetS and ORC risk were highly suggestive (four) or suggestive (six), while the rest were classified as weak (seven) or nonsignificant (eight). One association was suggestive for MetS and ORC survival, while the rest were classified as weak (three) or nonsignificant (one). The Egger's and excess significance tests were significant for 8(32%) associations between MetS and ORC risk and 3(60%) associations between MetS and ORC survival. CONCLUSION: This umbrella review suggests metabolic syndrome increases the risk of several obesity-related cancers and worsens colorectal cancer survival. Despite study variability, consistent associations across diverse populations highlight the urgency of prevention and management strategies targeting metabolic dysfunction to reduce cancer burden. Summary In this umbrella review, highly suggestive and suggestive evidence supports associations between MetS and the risk and survival of several obesity-related cancers. However, a better understanding of the relationship between metabolic syndrome and obesity-related cancers is still needed to provide appropriate clinical care, design optimal interventions, and prevent subsequent increases in the risks of cancer, morbidity, and mortality.