Metabolic syndrome and risk of monoclonal gammopathy of undetermined significance: a large Korean cohort study.

Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant plasma cell disorder with a risk of progression to multiple myeloma. Metabolic syndrome (MetS) is implicated in cancer development, yet its association with MGUS remains unclear. We examined MetS as a risk factor for MGUS in a large Korean cohort. In a retrospective cohort study using the National Health Information Database, we analyzed 4,453,504 adults undergoing health checkups in 2012, followed through up to 2022. MetS was defined by NCEP-ATP III criteria. Over a median 9.3-year follow-up, 1,241 MGUS cases were identified. MetS was associated with a 28% increased MGUS risk (hazard ratio [HR]=1.28; 95% confidence interval [CI]: 1.14- 1.44). Risk escalated with more MetS components, peaking at 76% for five components (HR=1.76; 95% CI: 1.35-2.30). Low high-density lipoprotein cholesterol, hypertension, and central obesity were key risk factors, with higher risks in males and younger adults (range, 20-39 years). Longitudinal analysis showed MetS onset (HR=1.25; 95% CI: 1.06-1.47) or persistence (HR=1.25; 95% CI: 1.06-1.48) increased MGUS risk compared to persistent MetS absence, whereas MetS resolution showed no significant risk increase over persistent MetS absence. MetS increases MGUS risk, particularly in males and younger individuals. Resolving MetS may mitigate MGUS risk, supporting targeted metabolic interventions.