Mass spectrometry-detected MGUS is associated with obesity and other novel modifiable risk factors in a high-risk population.

Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant condition of multiple myeloma with few known risk factors. The emergence of mass spectrometry (MS) for the detection of MGUS has provided new opportunities to evaluate its risk factors. 2628 individuals at elevated risk for multiple myeloma were enrolled in a screening study and completed an exposure survey (PROMISE; ClinicalTrials.gov, #NCT03689595). Participant samples were screened by MS, and monoclonal proteins (M-proteins) with concentrations >0.2 g/L were categorized as MS-MGUS. Multivariable logistic models evaluated associations between exposures and MS outcomes. Compared to normal weight (BMI: 18.5 to <25 kg/m2), obesity (BMI: >30 kg/m2) was associated with MS-MGUS, adjusting for age, sex, Black race, education, and income (odds ratio [OR] = 1.73, 95% confidence interval [CI] = 1.21 to 2.47, P = .003). High physical activity (>73.5 MET-hours/week vs. <10.5 MET-hours/week) had a decreased likelihood of MS-MGUS (OR = 0.45, 95% CI = 0.24 to 0.80, P = .009), whereas heavy smoking and short sleep had increased likelihood of MS-MGUS (>30 pack-years vs. never smoker: OR = 2.19, 95% CI = 1.24 to 3.74, P = .005 and sleep <6 vs. >6 hours/day: OR = 2.11, 95% CI = 1.26 to 3.42, P = .003). In the analysis of all MS-detected monoclonal gammopathies, which are inclusive of M-proteins with concentrations <0.2 g/L, elevated BMI and smoking were associated with all MS-positive cases. Findings suggest MS-detected monoclonal gammopathies are associated with a broader range of modifiable risk factors than what has been previously identified.