Metabolic syndrome and risk of advanced colorectal adenomas in a screening population: Frequentist and Bayesian analyses.

[BACKGROUND] Screening colonoscopy prevents colorectal cancer (CRC) by detecting and removing premalignant lesions. Metabolic syndrome (MetS) has been proposed as an additional risk marker to refine risk stratification beyond age-based screening, but its independent association with advanced colorectal neoplasia remains uncertain.

[METHODS] We conducted a cross-sectional analysis of asymptomatic adults undergoing screening colonoscopy in the Salzburg Colon Cancer Prevention Initiative. Analyses were limited to participants with complete-case data for the Adult Treatment Panel III (ATP III) MetS definition (N = 4891). The primary endpoint was advanced colorectal lesions, defined as advanced adenoma and/or CRC. We estimated incidence rate ratios (IRR) using Poisson regression with robust variance in unadjusted, age/sex-adjusted and fully adjusted models (demographic and lifestyle covariates). Sensitivity analyses applied the International Diabetes Federation (IDF) MetS definition and insulin resistance (HOMA-IR; binary and per doubling). In an exploratory subsample, leptin (per doubling) was evaluated, including joint models with MetS. Bayesian models (non-informative, pessimistic, sceptical priors) quantified posterior effect distributions and equivalence probabilities.

[RESULTS] Advanced lesions occurred in 389/4891 participants (7.95%) and were more frequent in ATP III MetS (9.66% vs. 6.97%; p = 0.001). In frequentist analyses, ATP III MetS was associated with advanced lesions in unadjusted models (IRR: 1.39; 95% CI, 1.15-1.68) but not after age/sex adjustment (IRR: 1.09; 95% CI, 0.90-1.32) or full adjustment (IRR: 1.06; 95% CI, 0.83-1.36). Age was the dominant predictor (fully adjusted IRR: 1.73 per decade; 95% CI, 1.53-1.95), while female sex was protective (IRR: 0.57; 95% CI, 0.44-0.73). Findings were concordant using the IDF definition (unadjusted IRR: 1.39; age/sex-adjusted 1.09; fully adjusted 1.07) and for HOMA-IR (binary: no association; per doubling: unadjusted IRR: 1.10, p = 0.052; adjusted null). In the leptin subsample (N = 602), leptin was not independently associated with advanced lesions (per doubling IRR: 0.85 unadjusted; 0.96 age/sex-adjusted; 0.95 fully adjusted) and did not materially alter MetS estimates. Bayesian analyses mirrored attenuation with adjustment; in fully adjusted models, sceptical priors yielded a posterior median IRR of 1.01 (95% CrI: 0.91-1.12) with a 92.9% probability that the MetS effect lay within ±10% of no effect.

[CONCLUSIONS] The apparent excess risk of advanced colorectal lesions in MetS is explained by age and sex. Across MetS definitions, HOMA-IR, leptin and Bayesian sensitivity analyses, MetS does not provide independent incremental information for CRC screening risk stratification beyond established demographic factors.