Obesity is an established, modifiable risk factor for the development of multiple myeloma (MM). Now, in a new study, researchers provide evidence that obesity may also be associated with the precursor to MM, monoclonal gammopathy of undetermined significance (MGUS). The research also shows an inverse association between high levels of physical activity and risk of MGUS. The work, published in Blood Advances, suggests that exercise or weight loss may help prevent the development of MM at earlier premalignant stages.
“While intriguing and hypothesis-generating, it is important to emphasize that this is a cross- sectional study that describes associations — and not causal mechanisms — between risk factors and disease,” said lead study author David J. Lee, MD, MPH, MMSc, of Massachusetts General Hospital in Boston.
MGUS is a premalignant clonal proliferation of plasma cells that precedes the development of MM. In routine clinical practice, individuals are not universally screened for MGUS, and it is unclear whether certain groups would benefit from additional surveillance. Obesity is an established and potentially modifiable risk factor for MM, yet studies have not established whether obesity is associated with increased risk of MGUS. Known risk factors of MGUS are older age, male sex, Black or African American race, and family history.
The researchers used mass spectrometry (MS) to analyze serum samples from the nationwide Predicting Progression of Developing Myeloma in a High-Risk Screened Population (PROMISE) study cohort of 2,628 individuals. They used the data to understand whether lifestyle factors — including physical activity, alcohol use, smoking, and sleep duration — as well as obesity and obesity-related comorbidities were associated with the prevalence of MGUS. MS is a relatively new method used to detect monoclonal proteins (M proteins), a biomarker for MGUS and MM, with high sensitivity.
After adjusting for age, sex, Black race, education, and income, the researchers observed that individuals who were obese had 73% higher odds of having MS-detected MGUS (MS-MGUS) compared to individuals of normal weight (odds ratio [OR] = 1.73, 95% CI 1.21-2.47; p=0.003). When adjusted for other metabolic comorbidities, the association between MGUS and obesity remained statistically significant, and the association was not modified by sex or physical activity level.
High levels of physical activity (equivalent to running or jogging 45-60 minutes or more per day) compared to the lowest level of physical activity (equivalent to walking less than 30 minutes per day) were inversely associated with MS-MGUS (OR=0.45, 95% CI 0.24-0.80; p=0.009).
“We were intrigued to find that having an elevated body mass index or BMI was associated with having MGUS in our study population, which is consistent with some but not all epidemiologic studies that evaluated obesity as a risk factor for MGUS,” Dr. Lee said. “We were also intrigued to observe that high levels of physical activity were inversely associated with having MGUS, even when adjusting for BMI.”
Heavy smoking and short sleep were also associated with the risk of MS-MGUS. Compared to never smoking, heavy smoking (more than 30 pack-years) was associated with MS-MGUS (OR=2.19, 95% CI 1.24-3.74; p=0.005). Short sleep (less than six hours per day) was also associated with MS-MGUS (OR=2.11, 95% CI 1.26-3.42; p=0.003) when compared to sleeping six or more hours per day.
These results are among the first to be reported for a high-risk population screened by MS for M proteins, providing preliminary hypothesis-generating data that need to be further studied, according to the authors.
“Our study may help generate hypotheses and fuel future investigations on how certain lifestyle factors may influence the development of MM and its precursor conditions,” Dr. Lee said. “We need more studies, including prospective and randomized controlled studies, to evaluate whether lifestyle interventions can impact myeloma-related outcomes.”
Any conflicts of interest declared by the authors can be found in the original article.
Reference
Lee DJ, El-Khoury H, Tramontano AC, et al. Mass spectrometry–detected MGUS is associated with obesity and other novel modifiable risk factors in a high-risk population [published online ahead of print 2024, Jan 11]. Blood Advances. doi: 10.1182/bloodadvances.2023010843.
