Abstract LB149: Metabolic syndrome and obesity-related cancer risk and survival: An umbrella review
Authors: Winn Maci , Karra Prasoona , Benson Ryzen , Pauleck Svenja , Chaiyakunapruk Nathorn , Khaing Win , Casucci Tallie , McFarland Mary M. , Hu-Lieskovan Siwen , Litchman Michelle , Xu Yizhe , Playdon Mary , Hardikar Sheetal 
Published: April 2024

Abstract
Background: Recent evidence suggests that metabolic syndrome (MetS) may be a potential risk factor for obesity-related cancer (ORC) owing to shared risk factors like physical inactivity, hyperglycemia, 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 incidence and survival.
Methods: The study protocol was registered with PROSPERO (CRD42021230899). Searches in five databases (Medline, Embase, CINAHL, Cochrane Library, and Scopus) retrieved 2,524 systematic reviews with meta-analyses (SRMA) after duplicates were removed. SRMA were eligible if they evaluated MetS with ORC incidence or survival, were conducted in an adult population (≥18 years), and included the pre-defined study-specific data. Using Covidence, two reviewers independently screened titles and abstracts (2,524) and then reviewed full text (41), selecting 23 SRMAs for inclusion. Data extraction was then completed independently by two reviewers. The outcomes were pooled using a random-effects model with the package “meta” in R. Sub-group analyses were conducted for a priori chosen factors, as outlined in the protocol. SRMA were appraised using the AMSTAR 2 criteria.
Results: 23 SRMA published between 2001 and 2023 met our inclusion criteria, comprising a total of 112 studies, ~52,543,335 total individuals, and ~355,808 ORC cases. After pooled analyses, MetS was associated with a statistically significant 10% increased risk of ORC [RR(95% CI): 1.10(1.06-1.14)]. MetS was also statistically significantly associated with poorer ORC-specific survival [RR(95% CI): 1.10(1.02-1.18)], though there was no association between MetS and overall survival [RR(95% CI): 1.04(0.97-1.11)]. When stratified by sex, both male and female individuals with MetS had a statistically significant higher risk of ORC [RR(95% CI): 1.12(1.06-1.17), 1.10(1.01-1.19), respectively]. When stratified by cancer site, individuals with MetS demonstrated a higher risk of colorectal cancer [RR(95% CI): 1.12(1.06-1.18)]. We also observed suggestive associations between MetS and liver, pancreatic, and postmenopausal breast cancer risk, but these were not statistically significant [RR(95% CI): 1.20(1.00-1.45), 1.20(0.96-1.50), 1.12(0.99-1.27), respectively]. All associations were supported by “critically low” quality evidence according to the AMSTAR2 criteria. This was primarily because these SRMAs either did not follow a pre-specified written and published protocol, or did not provide a list of all potentially relevant studies that were read in full-text form but excluded from the review.
Conclusions: These results emphasize the important role that MetS may play in the development of ORC as well as in the survival of patients with ORC. Conducting high-quality reviews is needed to increase the certainty of evidence, reduce potential bias, and improve knowledge in this field.
Citation Format: Maci Winn, Prasoona Karra, Ryzen Benson, Svenja Pauleck, Nathorn Chaiyakunapruk, Win Khaing, Tallie Casucci, Mary M. McFarland, Siwen Hu-Lieskovan, Michelle Litchman, Yizhe Xu, Mary Playdon, Sheetal Hardikar. Metabolic syndrome and obesity-related cancer risk and survival: An umbrella review [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB149.