Obesity linked to higher rates of a common precursor to multiple myeloma
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Key takeaways:
- Individuals with obesity and heavy smokers had higher rates of MGUS, a precursor to multiple myeloma.
- Highly active individuals had lower rates of MGUS.
Monoclonal gammopathy of undetermined significance, a common precursor to multiple myeloma, developed significantly more in individuals with obesity, according to a study published in Blood Advances.
Those who smoked heavily and those who slept less than 6 hours per day had a higher occurrence of monoclonal gammopathy of undetermined significance (MGUS) as well, while physically active individuals had lower rates.
“While obesity is an established modifiable risk factor for multiple myeloma, the data have not yet been clear regarding its association with myeloma precursor conditions,” David J. Lee, MD, MPH, MMSc, internal medicine resident at Massachusetts General Hospital, told Healio.
“Our study contributes one further piece of evidence that obesity may also be associated with MGUS,” he added. “We also observed that high levels of physical activity had an inverse association with MGUS risk, raising the question of whether lifestyle-related interventions — such as weight loss or exercise — may help prevent the development of multiple myeloma at earlier premalignant stages.”
Background and methodology
Physicians do not usually screen for MGUS — a premalignant clonal proliferation of plasma cells — because it generally develops without symptoms, according to background information provided by researchers.
Risk factors for MGUS include being male, Black, of older age and having a family history.
Obesity has been proven to be a risk factor for multiple myeloma, but researchers sought to determine its connection to MGUS.
“Despite significant advancements in treatment, multiple myeloma is still considered an incurable disease, and by the time it is diagnosed, many patients are already found to have complications and signs of end-organ damage from the disease,” Lee said. “A better understanding of MGUS risk factors may provide opportunities for identifying lifestyle-related prevention strategies for MGUS and multiple myeloma.”
Lee and colleagues conducted a retrospective cross-sectional analysis using data from the nationwide Predicting Progression of Developing Myeloma in a High-Risk Screened Population (PROMISE) study to build their cohort.
To be eligible for the screening study, individuals had to be Black or have a family history of hematologic malignancy or a multiple myeloma precursor condition. Enrollees could be included starting at age 18 years if they had two family members with a family history of hematologic malignancy; otherwise, participants had to be at least 30 years of age.
The study population included 2,628 individuals enrolled from across the country between February 2019 and March 2022 (76.8% 50 years and older; 73% women; 92.9% white; 6% Black).
Researchers used mass spectrometry over serum protein electrophoresis supplemented by immunofixation, which previous studies had used, due to superior detection of monoclonal proteins by mass spectrometry.
“Mass spectrometry is a novel method of detecting monoclonal proteins, allowing us to identify more patients with monoclonal gammopathies, such as MGUS, with greater sensitivity and at smaller M-protein concentration levels,” Lee said.
“While mass spectrometry is a powerful tool, we need to be very careful about how we utilize it to screen, diagnose and monitor patients,” he added. “Just because we are able to detect more individuals with monoclonal gammopathies does not necessarily mean they will have better outcomes.”
Results and next steps
After adjusting for various demographics, individuals with obesity had 73% higher odds of MGUS (OR = 1.73; 95% CI, 1.21-2.47).
Additionally, individuals classified as heavy smokers (OR = 2.19; 95% CI = 1.24-3.7) and those who slept less than 6 hours per day (OR = 2.11; 95% CI, 1.26-3.42) had increased odds of MGUS.
Conversely, physically active individuals had decreased rates of MGUS (OR = 0.45; 95% CI, 0.24-0.8).
Lee said he and his fellow researchers “were intrigued” by the results.
Study limitations included the limited Black population in the cohort, the high-risk demographic of the participants and the cross-sectional study design, which could allow “for the possibility of reverse causation between the main exposures and outcomes,” researchers wrote.
“Our present study is a cross-sectional study that can, at best, describe the associations, not causal mechanisms, between risk factors and the risk of MGUS,” Lee said.
“We need prospective studies and randomized controlled trials to answer important questions, including whether intervening on these lifestyle factors, such as weight loss or exercise, can help lower the risk for MGUS and multiple myeloma,” he added. “We also need more mechanistic studies investigating the pathophysiologic and etiologic mechanisms underlying these associations.”
For more information:
David J. Lee, MD, MPH, MMSc, can be reached at djlee@mgh.harvard.edu.
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