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Prevalence of Monoclonal Gammopathy of Undetermined Significance
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BACKGROUND: The prevalence of monoclonal gammopathy of undetermined significance (MGUS), a premalignant plasma-cell disorder, among persons 50 years of age or older has not been accurately determined. We used sensitive laboratory techniques to ascertain the prevalence of MGUS in a large population in a well-defined geographic area. METHODS: We identified all living residents of Olmsted County, Minnesota, as of January 1, 1995. We obtained serum that remained after the performance of routine clinical tests at Mayo Clinic or asked subjects for whom such serum was unavailable to provide a sample. Agarose-gel electrophoresis was performed on all serum samples, and any serum sample with a discrete band of monoclonal protein or thought to have a localized band was subjected to immunofixation. RESULTS: Serum samples were obtained from 21,463 of the 28,038 enumerated residents 50 years of age or older (76.6 percent). MGUS was identified in 694 (3.2 percent) of these persons. Age-adjusted rates were higher in men than in women (4.0 percent vs. 2.7 percent, P<0.001). The prevalence of MGUS was 5.3 percent among persons 70 years of age or older and 7.5 percent among those 85 years of age or older. The concentration of monoclonal immunoglobulin was less than 1.0 g per deciliter in 63.5 percent and at least 2.0 g per deciliter in only 4.5 percent of 694 persons. The concentration of uninvolved immunoglobulins was reduced in 27.7 percent of 447 persons tested, and 21.5 percent of 79 tested had a monoclonal urinary light chain. CONCLUSIONS: Among residents of Olmsted County, Minnesota, MGUS was found in 3.2 percent of persons 50 years of age or older and 5.3 percent of persons 70 years of age or older.
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“This tumor does not develop rapidly; instead, it may take decades for symptoms and organ damage to manifest.4-8”
From Evolution of Multiple Myeloma from a Genomic Perspective (2026) · cites this paper as [5]
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“MM is well-described to be universally preceded by precursor states, often decades before it is even diagnosed.”
From Evolution of Multiple Myeloma from a Genomic Perspective (2026) · cites this paper as [5]
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“Several epidemiological studies have shown that patients with MGUS and SMM might experience progression to MM over an extremely variable timeframe. Some patients progressed to MM within 2 years of diagnosis, while others may progress after 10 to 20 years or might never progress at all.4-6,75”
From Evolution of Multiple Myeloma from a Genomic Perspective (2026) · cites this paper as [5]
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“Monoclonal Gammopathy of Undetermined Significance Monoclonal gammopathy of undetermined significance (MGUS) occurs in 5% of persons older than age 50 years.(138) The criteria for MGUS have been defined previously in the literature.”
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“In a recent Mayo Clinic study that included residents of Olmsted County, MN, the prevalence of MGUS was 3% and 6% in patients aged older than 50 and 70 years, respectively [ 21 ].”
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“2% in the Caucasian general population 50 years of age or older.(1) It is characterized by the presence of a monoclonal immunoglobulin (M-protein) in individuals lacking evidence of multiple myeloma (MM) or other lymphoproliferative malignancies.”
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Monoclonal gammopathy: natural history studied with a retrospective approach
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“The frequency of MGUS in controls was similar to that reported in several other studies.(1) As would be expected, the prevalence of detectable prodromal MG was higher in samples collected within 10 years of diagnosis.”
BackgroundResultDiseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus
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“On average, about 1% of MGUS patients will go on to develop MM each year [27,28].”
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“2%, which corresponds to grossly twice that of the general population of this age group (2).”
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“function declines with age [14], and the prevalence of monoclonal gammopathy of undetermined significance, including the newly recognized light chain subtype, increases [15, 16].”
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“In other patients, a monoclonal gammopathy may represent a coincidental finding, as monoclonal gammopathies of undetermined significance occur in 3% of individuals above age 50 [34].”
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“At an approximate annual rate of 1% MGUS progresses to MM, lymphoplasmacytic lymphoma/ Waldenström macroglobulinemia or amyloid light chain amyloidosis (AL amyloidosis) (Kyle et al. 2006; Dispenzieri et al. 2010).”
BackgroundMonoclonal Gammopathy of Undetermined Significance: Current Concepts and Future Prospects
Seth, S., Zanwar, S., Vu, L., & Kapoor, P. (2020) · Current Hematologic Malignancy Reports · doi:10.1007/s11899-020-00569-2 · Cited by 14
Venous thromboembolism in patients with monoclonal gammopathy of undetermined significance.
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“46% compared with that reported for whites and blacks but is comparable to that in Asian populations.(3-6,8,9,19) Because the screening studies for MGUS have enrolled populations with widely variable age ranges, we evaluated the prevalence of MGUS in separate age brackets across the studies.”
ResultRacial disparities, cancer and response to oxidative stress
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“For instance, in a community-based study of AAs and CAs, AAs had significantly greater levels of oxidative stress compared to CAs after controlling for differences in inflammation and risk factors for cardiovascular disease (Morris et al., 2012).”
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“The standard definition of HC-MGUS and LC-MGUS used in prior Olmsted County prevalence studies were applied (Kyle et al, 2006; Dispenzieri et al, 2010).”
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Siepen, F. A. D., & Hansen, T. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13195873 · Cited by 13
“In addition, in the population aged >70 years, monoclonal gammopathy of undetermined significance (MGUS) can be detected in >5% of cases [23].”
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Naddaf, E., Dasari, S., Selcen, D., Charlesworth, M. C., Johnson, K. L., Mauermann, M. L., & Kourelis, T. (2022) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.51527 · Cited by 13
“A causal relationship between the plasma cell disorder and SLONM has not been well established, especially since MPs are also identified in 3– 5% of the general population of the same age.(6) However, the higher than expected frequency of an MP in SLONM raises suspicion for association between the two entities.”
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Peripheral Neuropathies Associated With Monoclonal Gammopathies
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“MGUS progresses to incurable multiple myeloma at a relentless rate of 1% per year (Kyle et al., 2006), yet little information is available about the molecular events that mediate this progression.”
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“2% over 50 years) and is higher in men and in Africans.(9,10) IgG is the commonest subtype (68.”
BackgroundInfluentialHematopoietic Tumors Primarily Presenting in Bone
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“2%) of monoclonal gammopathy in the general population [18].”
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Caers, J., Vekemans, M., Bries, G., Beel, K. A., Delrieu, V., Deweweire, A., Demuynck, H., Prijck, B. D., Samblanx, H. D., Kentos, A., et al. (2013) · Annals of Medicine · doi:10.3109/07853890.2013.801562 · Cited by 13
Cherry, B. M., Costello, R., Zingone, A., Burris, J. K., Korde, N., Manasanch, E. E., Kwok, M., Annunziata, C. M., Roschewski, M. J., Engels, E. A., et al. (2012) · American Journal of Hematology · doi:10.1002/ajh.23355 · Cited by 13
“The Mayo Clinic has determined the prevalence of MGUS to be approximately 3% in whites aged 50 years or older [4], and in follow-up studies has reported serum free light chain (FLC) abnormalities to be present in this group among persons with and without ‘‘conventional’’ heavy-chain MGUS, increasing the overall preval…”
BackgroundGaucher disease and dysgammaglobulinemia: A report of 61 patients, including 18 with GD type III
Jurecka, A., Gregorek, H., Kleinotienė, G., Czartoryska, B., & Tylki‐Szymańska, A. (2010) · Blood Cells Molecules and Diseases · doi:10.1016/j.bcmd.2010.07.015 · Cited by 13
Chi, K.-Y., Song, J., Desphande, S., Lee, P., Soni, A., Gonzales-Uribe, A., Lessa, Y., Morgan, A. A., Chang, Y., Lin, Y.-S., et al. (2025) · JAMA Network Open · doi:10.1001/jamanetworkopen.2025.17541 · Cited by 12
Sporadic Late-Onset Nemaline Myopathy: Current Landscape
Nicolau, S., & Milone, M. (2023) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-023-01311-0 · Cited by 12
“Moreover, monoclonal gammopathy occurs in approximatively 3% of individuals older than 50 years, making it a poorly specific biomarker of SLONM [31].”
BackgroundYONEZAWA, S., Haruki, T., Koizumi, K., Taketani, A., Oshima, Y., Oku, M., Wada, A., Sato, T., Masuda, N., Tahara, J., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25031570 · Cited by 12
“Approximately 5.3% of individuals older than 70 years old have MGUS [5], and about 1% of MGUS progresses to MM each year [6].”
BackgroundInfluentialPinney, J. H., Roufosse, C. A., Kousios, A., Chaidos, A., Gillmore, J. D., Rainone, F., Choudhuri, S., Ramasamy, K., Blakey, S., Ashcroft, J., et al. (2025) · British Journal of Haematology · doi:10.1111/bjh.19956 · Cited by 12
Treatment of newly diagnosed multiple myeloma: advances in current therapy
Kumar, S. K. (2009) · Medical Oncology · doi:10.1007/s12032-009-9370-1 · Cited by 12
“This condition, commonly referred to as monoclonal gammopathy of undetermined significance (MGUS), can be present for varying durations and may or may not be identified before the diagnosis of myeloma is made [9].”
BackgroundProteomic analysis of multiple myeloma: Current status and future perspectives
Ge, F., Bi, L., Tao, S., Xu, X., Zhang, Z., Kitazato, K., & Zhang, X. (2010) · PROTEOMICS - CLINICAL APPLICATIONS · doi:10.1002/prca.201000044 · Cited by 12
“Although gene expression profiling has provided novel insights into the understanding the pathogenesis of MM, ultimately Abbreviations: apoC-I, apolipoprotein C-I; ATO, arsenic trioxide; BM, bone marrow; FGFR3, fibroblast growth factor receptor 3; MGUS, monoclonal gammopathy of undetermined clinical significance; MM,…”
BackgroundInfluentialMa, L., Xu, S., Qu, J., Hou, J., Wang, Y., Wen, L., Liu, Y., Kang, Y., Jiang, M. Y., Fu, W., et al. (2018) · Hematological Oncology · doi:10.1002/hon.2548 · Cited by 12
“8%, and significantly increases with age.(2-13) The prevalence and type of immunoglobulin may be different between different races.”
BackgroundInfluentialBelouni, R., Allam, I., Cherguelaîne, K., Berkani, L. M., Belaid, B., Berkouk, Y., Nekkal, S. M., Saidani, M., Belhani, M. F., Ghaffor, M., et al. (2019) · Current Research in Translational Medicine · doi:10.1016/j.retram.2019.11.003 · Cited by 12
Jin, Y., Savage, N. M., Bollag, R. J., Xu, H., & Singh, G. (2021) · The Journal of Applied Laboratory Medicine · doi:10.1093/jalm/jfab090 · Cited by 12
A polygenic risk score for multiple myeloma risk prediction
Canzian, F., Piredda, C., Macauda, A., Zawirska, D., Andersen, N. F., Nagler, A., Zaucha, J. M., Mazur, G. J., Dumontet, C., Wątek, M., et al. (2021) · European Journal of Human Genetics · doi:10.1038/s41431-021-00986-8 · Cited by 12
“MM is preceded by monoclonal gammopathy of undetermined significance (MGUS), an asymptomatic premalignant condition [2, 3], and by smoldering myeloma (SM), a more advanced precursor of the disease [4].”
BackgroundChang, V. C., Khan, A. A., Huang, W., Katki, H. A., Purdue, M. P., Landgren, O., & Hofmann, J. N. (2022) · Blood Cancer Journal · doi:10.1038/s41408-022-00642-4 · Cited by 12
“MGUS affects approximately 2–3% of the general US population 50 years of age or older [3, 4] and has an estimated annual average risk of progression of 1% [5].”
BackgroundLécluse, Y., Comby, E., Mariotte, D., Tual, S., Mauff, B. L., Lebailly, P., & Gauduchon, P. (2015) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.3109/10428194.2015.1113277 · Cited by 12
“23%; kappa: 57%; lambda: 43%).[2,4] Two men had”
MethodMultimodality imaging of osseous involvement In haematological malignancies
Keraliya, A. R., Krajewski, K. M., Jagannathan, J. P., Shinagare, A. B., Braschi‐Amirfarzan, M., Tirumani, S. H., & Ramaiya, N. H. (2016) · British Journal of Radiology · doi:10.1259/bjr.20150980 · Cited by 12
Targeting plasma cells: are we any closer to a panacea for diseases of antibody‐secreting cells?
Low, M. S. Y., Infantino, S., Grigoriadis, G., & Tarlinton, D. M. (2016) · Immunological Reviews · doi:10.1111/imr.12388 · Cited by 13
“It is also possible to detect a ‘light chain MGUS’ that presumably precedes light chain myeloma, which comprises approximately 20% of all new myeloma diagnoses (70).”
BackgroundInfluentialBarceló, F., Gomila, R. M., de Paúl, I., Gili, X., Segura, J., Pérez-Montaña, A., Jimenéz‐Marco, T., Sampol, A., & Portugal, J. (2018) · PLoS ONE · doi:10.1371/journal.pone.0201793 · Cited by 12
Schmidt, B., Debold, E., Frank, M., Arendt, M., Dragano, N., Dürig, J., Dührsen, U., Moebus, S., Erbel, R., Jöckel, K., et al. (2019) · Annals of Hematology · doi:10.1007/s00277-019-03825-5 · Cited by 12
Biochemistry, Immunoglobulin M
Sathe, A. R., & Cusick, J. (2021) · StatPearls · Cited by 12
Monoclonal gammopathy of undetermined significance and COVID-19: a population-based cohort study
Rögnvaldsson, S., Eyþórsson, E. S., Þorsteinsdóttir, S., Viðarsson, B., Onundarson, P. T., Agnarsson, B. A., Sigurðardóttir, M. S., Þorsteinsdóttir, I., Ólafsson, Í., Runolfsdottir, H. L., et al. (2021) · Blood Cancer Journal · doi:10.1038/s41408-021-00580-7 · Cited by 12
“These findings are important since MGUS is the most common precursor condition of hematological malignancy, affecting millions of individuals worldwide [11, 12].”
BackgroundJurczyszyn, A., & Suska, A. (2019) · Reference Module in Biomedical Sciences · doi:10.1016/b978-0-12-801238-3.11412-6 · Cited by 13
Monoclonal Gammopathy of Undetermined Significance: An Update for Nephrologists
Parry, H., Pratt, G., & Hutchison, C. A. (2012) · Advances in Chronic Kidney Disease · doi:10.1053/j.ackd.2012.07.006 · Cited by 12
Overview of monoclonal gammopathies of undetermined significance
Vogt, R. F., & Marti, G. E. (2007) · British Journal of Haematology · doi:10.1111/j.1365-2141.2007.06860.x · Cited by 12
“However, some overlap in these outcomes is evident from the extensive studies of MGUS (Kyle, 1978, 1993; Kyle et al, 2002, 2004, 2006) and the much more limited studies of MBL. MGUS can occasionally progress to CLL or non-Hodgkin lymphoma (NHL), and at least one report describes a case of MBL that…”
Jasiński, M., Biliński, J., & Basak, G. W. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.853540 · Cited by 12
“In 3-4% of the whole population over the age of 50, the diagnosis of MGUS could be stated (3).”
BackgroundCárdenas, M. C., García‐Sánz, R., Puig, N., Pérez-Surribas, D., Flores-Montero, J. A., Ortiz-Espejo, M., de la Rubia, J., & Cruz-Iglesias, E. (2023) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2023-0326 · Cited by 11
Systematic review and meta-analysis of the clinical features of MGRS
Du, J., & Hu, Z. (2024) · BMC Nephrology · doi:10.1186/s12882-024-03458-5 · Cited by 11
“The estimated prevalence of MGUS was 3.2% in individuals > 50 years and 5.3% in those > 70 years [18].”
InfluentialRögnvaldsson, S., Gasparini, A., Þorsteinsdóttir, S., Sverrisdottir, I. S., Eyþórsson, E. S., Long, T. E., Pálmason, R., Viðarsson, B., Onundarson, P. T., Agnarsson, B. A., et al. (2024) · British Journal of Haematology · doi:10.1111/bjh.19957 · Cited by 12
Voigtlaender, M., Vogler, B. K., Trepel, M., Panse, J., Jung, R., Bokemeyer, C., Bacher, U., & Binder, M. (2015) · Annals of Hematology · doi:10.1007/s00277-015-2409-9 · Cited by 11
“7 %) as compared to previous studies [10].”
BackgroundResultMuchtar, E., Kumar, S. K., Magen, H., & Gertz, M. A. (2017) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.1080/10428194.2017.1334124 · Cited by 11
“MGUS is a common finding, found in approximately 3% of the population over the age of 50 [28].”
BackgroundThe Role of the Gut Microbiome in Pathogenesis, Biology, and Treatment of Plasma Cell Dyscrasias
Jasiński, M., Biliński, J., & Basak, G. W. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.741376 · Cited by 11
“2% of the population aged over 50 years (2).”
BackgroundVià, M. D., Lionetti, M., Marella, A., Matera, A., Travaglino, E., Signaroldi, E., Galbussera, A. A., Lucca, U., Mandelli, S., Riva, E., et al. (2022) · Blood Advances · doi:10.1182/bloodadvances.2021006498 · Cited by 11
“8 NOVEMBER 2022 • VOLUME 6, NUMBER 21 median age of the cohort was aged 91 years (range, 81-104), significantly higher than other previously published MGUS studies.(11) Other clinical and laboratory features of the cohort are shown in Table 1.”
Result
Metadata
- Authors
- Kyle, R. A., Therneau, T. M., Rajkumar, S. V., Larson, D. R., Plevak, M. F., Offord, J. R., Dispenzieri, A., Katzmann, J. A., & Melton, L. J.
- Affiliations
- Mayo Clinic (US)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2006-03-30
- Volume
- 354
- Issue
- 13
- Pages
- 1362-1369
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2086990334
- Cited by
- 1,423
- References
- 22
- Citations by year
- 2026: 56 · 2025: 80 · 2024: 90 · 2023: 71 · 2022: 83 · 2021: 88 · 2020: 93 · 2019: 77 · 2018: 64 · 2017: 73 · 2016: 66 · 2015: 60 · 2014: 66 · 2013: 78 · 2012: 70
- FWCI
- 33.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA 107 476, CA6 2242, R01CA107476, P01CA062242)
- Topics
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Health Sciences › Medicine › Hematology › Chronic Lymphocytic Leukemia Research
- Health Sciences › Medicine › Internal Medicine › Amyloidosis: Diagnosis, Treatment, Outcomes
- Keywords
- monoclonal gammopathy of undetermined significance, prevalence, plasma cell dyscrasia, M protein, serum protein electrophoresis, immunofixation, age differences, Olmsted County, Minnesota
- MeSH terms
- Aged, Aged, 80 and over, Female, Humans, Immunoglobulin A, Immunoglobulin G, Immunoglobulin M, Male, Middle Aged, Minnesota, Paraproteinemias, Prevalence, Age Distribution, Sex Distribution
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