Mass spectrometry screening reveals high MGUS prevalence among Black South Africans in Soweto

A landmark screening study conducted in Soweto, South Africa, has found that Black South Africans carry one of the highest documented burdens of monoclonal gammopathy of undetermined significance, or MGUS, an asymptomatic blood condition that precedes the incurable bone marrow cancer multiple myeloma. The research, published in eClinicalMedicine, is the largest investigation of monoclonal gammopathies ever carried out in sub-Saharan Africa and used highly sensitive mass spectrometry to detect the faint molecular fingerprints of the condition in ordinary blood samples. The findings suggest that Black South Africans may represent a high-risk population comparable to, and in some age groups exceeding, the best-known high-risk groups in the United States, with potentially far-reaching implications for how early detection of multiple myeloma is approached across the African continent.

MGUS is a precursor state in which a small clone of plasma cells in the bone marrow secretes identical copies of immunoglobulins or free light chains, known as M-proteins, into the bloodstream. The condition itself causes no symptoms, but it is the obligatory first step on the path to multiple myeloma, a malignancy that can trigger kidney failure, destructive bone lesions, anaemia and dangerously elevated calcium levels. Despite major therapeutic advances, myeloma remains incurable, which is why identifying who carries the precursor condition has become a central question in cancer epidemiology. In the United States, Black individuals are diagnosed with myeloma at roughly twice the rate of White individuals and at younger ages, and screening studies have shown correspondingly elevated MGUS prevalence, with the disparities most pronounced in younger age groups.

Whether Black populations in sub-Saharan Africa share this elevated risk has been far less clear. Only a handful of screening studies had been conducted in the region, and their results were mixed. Studies of 917 men in Ghana and 386 men in Johannesburg each found roughly a two-fold higher MGUS prevalence compared with a White reference population from Olmsted County, Minnesota. Yet a study of 515 individuals in Eswatini reported a heavy-chain MGUS prevalence similar to the Olmsted County figure, while simultaneously reporting a strikingly high light-chain MGUS prevalence of 12.3 percent, a discrepancy speculated to reflect overdiagnosis caused by free light chain reference ranges that may not be valid for racially diverse populations. These methodological uncertainties left the true burden of monoclonal gammopathies in Africa unresolved.

To close this gap, the PROMISE South Africa team enrolled 2,004 Black South Africans aged 40 to 75 at a community screening site in Soweto, an urban settlement of more than one million people in southwestern Johannesburg. Between January 2021 and August 2023, every participant provided a blood sample and completed an interview-guided survey covering sociodemographic background, comorbidities and lifestyle exposures. Samples were processed at the Sydney Brenner Institute for Molecular Bioscience at the University of the Witwatersrand and shipped to the Dana-Farber Cancer Institute, where they were analysed with the EXENT platform, which uses matrix-assisted laser desorption ionisation-time of flight mass spectrometry to identify and quantify M-proteins. This technique detects proteins at concentrations far below the threshold of conventional serum protein electrophoresis, and prior calibration work established that M-proteins quantified by mass spectrometry at 0.2 grams per litre or above correspond to the detection level of conventional assays.

The results were striking. Heavy-chain MGUS was detected in 12 percent of participants, with a median M-protein concentration of 0.76 grams per litre, and the great majority of these proteins were immunoglobulin G, accounting for 85 percent of cases, followed by IgA and IgM. Light-chain MGUS was found in a further 3 percent, most commonly involving kappa light chains. Combined, roughly 15 percent of this middle-aged Soweto cohort carried detectable monoclonal proteins. Prevalence rose with age, and participants living with HIV, who made up 26 percent of the cohort, were significantly more likely to have MGUS than those without the virus. In multivariable models adjusted for age, sex, education, poverty and ethnic-linguistic group, each additional decade of life was associated with 22 percent higher odds of MGUS, while HIV infection was associated with 67 percent higher odds, an association that persisted in sensitivity analyses.

The international comparison placed these numbers in context. The investigators pooled their Soweto data with two US cohorts screened with identical methods: the PROMISE US study of Black Americans and non-Black individuals with a family history of haematological malignancy, and the Mass General Brigham Biobank. Among 3,726 Black individuals aged 40 to 75 across both countries, the adjusted predicted prevalence of MGUS was 17 percent for Black South Africans, compared with 13 percent for Black Americans and 10 percent for non-Black Americans with a positive family history. The differences were most dramatic in the youngest age band: among participants aged 40 to 49, Black South Africans had a markedly higher prevalence than Black Americans, while at older ages the two groups converged. Against the family-history group, Black South Africans showed higher prevalence across every age category.

The study also probed which modifiable exposures might shape this risk, yielding several unexpected signals. Obesity, often considered a myeloma risk factor, was associated with 41 percent lower odds of MGUS in this population, a counterintuitive result the authors attribute to the difficulty of interpreting body mass index in a community experiencing a double burden of malnutrition, where undernutrition and overnutrition coexist and childhood stunting remains common. By contrast, high physical activity, equivalent to running or jogging 30 to 45 minutes daily, was associated with 57 percent lower odds of MGUS, consistent with prior US findings and with the anti-inflammatory and metabolic effects of exercise. Smoking emerged as a clear risk factor: past or current smokers had 61 percent higher odds of MGUS than never smokers, with risk rising from light-to-moderate to heavy smoking histories, plausibly reflecting chronic antigenic stimulation of the immune system.

Alcohol told a more complicated story. Heavy consumption of 15 grams or more per day was associated with 40 percent higher odds of MGUS in models adjusted for sociodemographic factors, and notably, 84 percent of the heavy drinkers reported binge or high-intensity drinking patterns in a typical month. However, when the analysis additionally adjusted for smoking pack-years, the alcohol association weakened and lost statistical significance, suggesting that it may partly reflect correlated smoking behaviours and other shared lifestyle exposures rather than a direct effect of alcohol itself. The authors caution that alcohol is not currently considered a myeloma risk factor and that the drinking patterns captured in prior studies have often been too crude to distinguish moderate consumption from the heavy episodic drinking prevalent in some urban, low-income settings.

A crucial methodological choice underpinned the light-chain findings. Rather than applying standard free light chain reference ranges, which were derived from a small cohort of blood donors and have been shown to overdiagnose light-chain MGUS in Black populations, the team used ranges optimised for racially diverse populations including people of African descent from the United States and South Africa. Earlier work showed this approach reduces light-chain MGUS overdiagnosis by 91 percent, cutting estimated prevalence from 10.7 percent to under 1 percent in pooled international cohorts. Data from the large Icelandic iStopMM screening study have similarly demonstrated that standard ranges lead to substantial overdiagnosis. Applying the refined ranges here likely yields a more realistic picture of the true light-chain disease burden, though the authors note it could modestly underestimate prevalence and call for validation in other African populations.

The study’s limitations include its cross-sectional design, which cannot establish whether the measured exposures preceded the development of MGUS, its reliance on convenience sampling at a single community site, and the absence of serial M-protein measurements to track changes over time. Residual confounding and limited generalisability to rural South Africa are further caveats. Nevertheless, the authors argue the evidence is strong enough to reframe thinking about global myeloma risk: Black South Africans appear to be a high-risk population, plausibly shaped by African ancestry, high HIV prevalence and specific lifestyle factors. If validated, these findings could justify targeted screening strategies in South Africa and open prevention avenues, including long-term virologic control of HIV, smoking cessation and promotion of physical activity, that might ultimately reduce the global burden of multiple myeloma.

Subject of Research: Prevalence and risk factors of monoclonal gammopathy of undetermined significance among Black South Africans screened by mass spectrometry

Article Title: MGUS in Black individuals in Soweto, South Africa screened by mass spectrometry: results of the PROMISE South Africa study

Article References: Lee, D. J., Chen, W. C., Bertamini, L., El-Khoury, H., Allam, S., Fleming, G., Alberge, J.-B., Perry, J., Davis, M. I., Lightbody, E., Goqwana, L. N., Philip, V., Pentz BRad, A., Dip Tchg, T. H., Redd, R., Sakrikar, D., Barnidge, D., Perkins, M. C., Harding, S., … Marinac, C. R. (2026). MGUS in Black individuals in Soweto, South Africa screened by mass spectrometry: results of the PROMISE South Africa study. eClinicalMedicine, 100, Article 104208. https://doi.org/10.1016/j.eclinm.2026.104208

Image Credits: AI Generated

DOI: 10.1016/j.eclinm.2026.104208

Keywords: MGUS, multiple myeloma, Soweto, South Africa, mass spectrometry, HIV, health disparities, plasma cell disorders, smoking, physical activity, cancer screening, epidemiology