Obesity, smoking, and poor sleep raise risk of myeloma precursor

Lifestyle factors seen as among those tied to condition known as MGUS

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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Obesity, a history of heavy smoking, and limited sleep are risk factors for developing monoclonal gammopathy of undetermined significance (MGUS), a precursor condition to multiple myeloma, a large U.S. study shows.

These findings will help inform future work to identify groups who “may benefit from targeted screening strategies, enhanced surveillance, and precision prevention strategies,” the researchers wrote.

The study, “Mass spectrometry-detected MGUS is associated with obesity and other novel modifiable risk factors in a high-risk population,” was published in the journal Blood Advances.

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Routine screening for MGUS, a risk factor for multiple myeloma, is not common

Multiple myeloma affects plasma cells, immune cells that play an important role in protecting the body against infections by producing antibodies.

MGUS, a type of monoclonal gammopathy, is characterized by the presence of an abnormal monoclonal or M protein. The disease is not routinely screened in clinical practice and often does not cause significant symptoms. Up to now, only a few risk factors for MGUS have been identified, including older age, male sex, Black race, and a family history of blood cancers.

“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,” David Lee, MD, an internal medicine resident at Massachusetts General Hospital and the study’s first author, said in an American Society of Hematology press release. “It’s preceded by premalignant conditions including MGUS.”

In 2020, the Centers for Disease Control and Prevention reported that nearly 42% of the U.S. population is obese, as assessed by a body mass index (BMI, a measure of body fat) of 30 or higher. While obesity is a well established risk factor for multiple myeloma, whether is also poses a risk of MGUS remains under debate.

“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,” Lee said.

A team led by researchers at Dana-Farber Cancer Institute in Boston assessed the link between obesity, obesity-related disorders, and lifestyle factors with the prevalence of MGUS and the risk of developing multiple myeloma.

The scientists conducted the first U.S. nationwide screening study, called PROMISE (NCT03689595), of people at high risk of multiple myeloma. Eligible participants were African Americans and/or adults (age 30 and older) with a family history of a blood-related condition or a precursor condition to multiple myeloma. Younger adults with two or more first-degree family members with a blood cancer or multiple myeloma precursor condition also were included.

Analysis included 2,628 participants, enrolled between February 2019 and March 2022, from across all U.S. states and the District of Columbia.

Specifically, MGUS was assessed using mass spectrometry — a technique that, according to the investigators, has superior sensitivity for detecting the M protein than previous approaches.

Obesity a factor not modified by sex or physical activity levels

Among these people, 237 had MGUS (9%). Statistical analysis showed an association between obesity and MGUS, after adjusting for age, sex, Black race, education, and income. Being obese was associated with a 73% higher risk of MGUS compared with individuals of normal weight.

“The association between obesity and MS-MGUS [disease detected by mass spectrometry] was not modified by sex or physical activity level,” the researchers added.

They then assessed the contribution of lifestyle factors to the risk of MGUS. A history of heavy smoking (over 30 pack-years, a measure of the number of packs smoked daily multiplied by the number of years that person has smoked) correlated with a significantly higher risk — 2.19 times higher — of developing MGUS compared with participants who never smoked.

A lack of sleep — less than six hours a day — also linked with a 2.11 times higher risk of MGUS relative to those with longer daily sleeping patterns. In contrast, very active participants — defined as the equivalent of running or jogging 45-60 minutes each day or more — were significantly less likely to have MGUS. In both cases, the association was maintained after adjusting for BMI, smoking history, and alcohol consumption.

“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 concluded. “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.