Patients with obesity may be more likely to have monoclonal gammopathy of undetermined significance, according to a recent study published by Lee et al in Blood Advances.
Background
Monoclonal gammopathy of undetermined significance—a benign hematologic condition characterized by an abnormal protein produced by plasma cells—is a known precursor to multiple myeloma. Although the majority of patients with monoclonal gammopathy of undetermined significance exhibit no significant symptoms, the presence of the condition may serve as a warning to monitor for the potential development of multiple myeloma.
In 2020, the U.S. Centers for Disease Control and Prevention reported that nearly 42% of the U.S. population had obesity, defined as a body mass index (BMI) of 30 kg/m2 or higher. However, there is still insufficient evidence to suggest that obesity may influence cancer outcomes.
“While significant advancements have been made in therapeutics for multiple myeloma, it remains an incurable disease, often diagnosed after patients have already experienced end-organ damage,” explained lead study author David Lee, MD, MPH, MMSc, an internal medicine resident at Massachusetts General Hospital. “It’s preceded by premalignant conditions including [monoclonal gammopathy of undetermined significance]. Our research group is focused on investigating risk factors and etiology of [the condition] to better understand who may be at increased risk for developing [it] and its progression to multiple myeloma,” he continued.
Study Methods and Results
In the recent study, investigators enrolled 2,628 U.S. patients at heightened risk of developing multiple myeloma based on their self-identified race and family history of hematologic malignancies between February 2019 and March 2022. The investigators then screened the patients for monoclonal gammopathy of undetermined significance—marked by the presence of monoclonal proteins at serum concentrations of 0.2 g/L or greater—and measured monoclonal gammopathy of undetermined significance using mass spectrometry.
After controlling for age, sex, race, education, and income, the investigators found that patients with obesity had a 73% higher likelihood of having monoclonal gammopathy of undetermined significance compared with patients with normal BMIs. This association remained unchanged when they accounted for physical activity. Nonetheless, highly active patients who partook in the equivalent of running or jogging 45 to 60 minutes per day or more were less likely to have monoclonal gammopathy of undetermined significance even after adjusting for BMI class, whereas those who reported heavy smoking and less sleep per night were more likely to have detectable levels of monoclonal gammopathy of undetermined significance.
Conclusions
The investigators noted that the limitations of the study included it was cross sectional and likened their findings to a snapshot of how certain variables or characteristics may relate to one another at a single point in time. Despite discovering a strong correlation among monoclonal gammopathy of undetermined significance, obesity, and lifestyle factors, the investigators did not have enough evidence to assume causation.
As a result of previous research suggesting BMI does not effectively distinguish between fat and lean mass and does not account for how fat is distributed throughout the body, the American Medical Association recently voted to adopt a new policy to no longer use the metric alone to assess whether patients have a healthy weight. The formula was created based on data from non-Hispanic White populations, suggesting its implications cannot accurately be generalized across Black, Asian, and Hispanic communities.
The investigators plan to validate their findings in future study cohorts, including in patients followed longitudinally, to better explore the mechanisms through which obesity and other modifiable risk factors may influence the development and progression of monoclonal gammopathy of undetermined significance.
“These results guide our future research in understanding the influence of modifiable risk factors such as weight, exercise, and smoking on cancer risk,” underscored Dr. Lee. “Before we can develop effective preventative health strategies to lower the risk of serious diseases like multiple myeloma, we first need to better understand the relationship between [monoclonal gammopathy of undetermined significance] and potentially modifiable risk factors like obesity,” he concluded.
Disclosure: For full disclosures of the study authors, visit ashpublications.org.
