Research has established that monoclonal gammopathy of undetermined significance (MGUS) is a premalignant condition of multiple myeloma (MM) with few known risk factors.

Findings from a nationwide screening study conducted in the United States and recently published in Blood Advances revealed that among individuals at elevated risk of MM, obesity, having a history of heavy smoking, and sleep issues are lifestyle risk factors for the manifestation of MGUS, which is the precursor condition to multiple myeloma.

For this study, the researchers evaluated individuals at elevated risk of MM who were screened by mass spectrometry and examined the impact of obesity, obesity-related comorbidities, and lifestyle factors and their correlation with the incidence of MGUS.

The PROMISE (Predicting Progression of Developing Myeloma in a High-Risk Screened Population) study involved individuals at high risk of MM.

Between February 2019 and March 2022, the study enrolled 2,628 participants from all 50 states and the District of Columbia who were at elevated risk of developing MM based on self-identified race and family history of hematologic malignancies.

The authors wrote, “Individuals were eligible to participate if they self-identified as (1) Black or of African descent or (2) non-Black but have a family history of hematological malignancy or MM precursor condition. Enrollment began at age 30 years, but for individuals with two or more first-degree family members with hematological malignancy or MM precursor condition, enrollment eligibility started at age 18 years.”

The authors also indicated that individuals with a prior diagnosis of MGUS, smoldering multiple myeloma, MM, Waldenström macroglobulinemia, and/or other malignancies requiring active therapy were excluded from this study. Participants were screened for MGUS, “defined by the presence of monoclonal proteins at serum concentrations of 0.2g/L or greater. Researchers measured MGUS using mass spectrometry—a novel, highly sensitive method of identifying and quantifying monoclonal proteins in the blood.”

The results revealed that after controlling for age, gender, race, education, and income, obesity was correlated with 73% greater odds of developing MS-MGUS when compared with individuals at normal weight.

The authors also noted that the correlation between obesity and MS-MGUS remained unchanged regardless of gender or level of physical activity.

The researchers also assessed the impact of lifestyle factors on the development of MGUS and discovered that among individuals who slept fewer than 6 hours per day, there was a 2.11 times greater risk of developing MGUS compared with those individuals who had longer daily sleeping patterns.

Among individuals with a history of heavy smoking (over 30 pack-years), there was a 2.19 times greater risk of developing MGUS compared with individuals who never smoked. Additionally, data revealed that very active individuals (such as those engaging in physical activity or exercising that is equivalent to running/jogging 45-60 minutes/day or more) were less likely to develop MGUS, and the correlation was sustained after adjusting for BMI, smoking history, and alcohol consumption.

Based on their findings, the authors concluded, “Our study of a U.S.-based cohort of high-risk individuals shows associations with novel, potentially modifiable risk factors (obesity, physical activity, heavy smoking, short sleep duration).”

The researchers also added, “These preliminary results will require validation and further investigation toward the effort of identifying groups that may benefit” from better screening strategies, surveillance, and prevention efforts.”

In a press release, David Lee, MD, MPH, MMSc, an internal medicine resident at Massachusetts General Hospital, stated, “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. It's preceded by premalignant conditions, including MGUS. Our research group is focused on investigating risk factors and etiology of MGUS to better understand who may be at increased risk for developing MGUS and its progression to multiple myeloma.”

Dr. Lee added, “These results guide our future research in understanding the influence of modifiable risk factors, such as weight, exercise, and smoking, on cancer risk. 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 MGUS and potentially modifiable risk factors like obesity.”

The researchers will conduct further studies to validate these findings, including individuals who are followed longitudinally, to explore further the mechanisms through which obesity and other modifiable risk factors might affect the development and progression of MGUS.

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