Obesity and Risk of Monoclonal Gammopathy of Undetermined Significance: A Population-Based Study

Background

Nearly all multiple myelomas (MM) are preceded by the premalignant state, monoclonal gammopathy of undetermined significance (MGUS), an asymptomatic condition that needs no treatment. The etiology of MGUS and MM is to a large extent unknown. Two studies on the association between obesity and MGUS have been conducted with conflicting results, despite a reported association between obesity and MM. The aim of this study was to determine if obesity is associated with an increased risk of MGUS and light-chain MGUS (LC-MGUS) in a population-based screened cohort of individuals above the age of 65 years using extensive number of markers for current and early life obesity.

Methods

This study was based on participants from the Age, Gene/Environment Susceptibility – Reykjavik Study (AGES-RS), which is a continuation of the Reykjavik Study, a population-based study performed by the Icelandic Heart Association. In 1967, the Reykjavik Study began recruiting a sample of over 30,000 residents of Reykjavik from the 1907-1935 birth cohorts. In 2002, the AGES-RS began recruiting 5,764 of the surviving members. Serum protein electrophoresis (SPEP) and serum free light-chain assay were performed on all subjects. Obesity measures were performed at baseline, and participants were additionally asked about their weight at the age of 25 years. The measures at baseline included were weight (kg), body mass index (BMI) (kg/m²), percent body fat, fat (kg), and fat-free mass (kg) from bioimpedance, total body fat area (cm²), visceral and subcutaneous fat area (cm²), and waist circumference (cm). The association with MGUS and LC-MGUS was analyzed using logistic regression and adjustment was made for age and sex. Cox proportional-hazard regression was performed to test whether obesity was a risk factor for progression from MGUS to MM and lymphoproliferative diseases.

Results

A total of 304 (5.3%) MGUS cases and 118 participants (2.1%) with LC-MGUS were identified. No association was found between any of the obesity markers and MGUS (Table). A statistically significant positive association was found between obesity (BMI ≥ 30 kg/m²) at study baseline and LC-MGUS (Table). Weak but statistically significant association was found between LC-MGUS and BMI at baseline, weight, max weight, percent body fat, fat in kg, fat-free mass, and waist circumference (Table). No association was found on risk of MGUS using joint effect of early adulthood BMI and BMI at study entry. Analysis on the effect of the obesity markers on the progression from MGUS to MM and lymphoproliferative diseases showed no association.

Conclusion

In this large population-based cross-sectional study aimed at evaluating the association between obesity and MGUS and LC-MGUS, we found obesity (BMI ≥ 30 kg/m²) to be associated with 2-fold excess risk for LC-MGUS. An association was additionally found between several of the obesity markers used and LC-MGUS. Future studies are needed to clarify underlying mechanisms for this finding. However, we did not find an association between any of the obesity markers and MGUS. Taken together, we were unable to confirm the previously reported association between MGUS and obesity.

*Adjusted for age and sex