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Prevalence of Monoclonal Gammopathy of Undetermined Significance
Open accessAbstract
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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“MM is always preceded by a condition known as monoclonal gammopathy of undetermined significance (MGUS) that displays a lifelong rate of progression of 1% per year [6,7] and is characterized by less than 10% PCs BM infiltration [8].”
BackgroundMonoclonal gammopathy in the setting of Pyoderma gangrenosum
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Shankar, M., & Yadla, M. (2024) · Frontiers in Nephrology · doi:10.3389/fneph.2024.1439288 · Cited by 3
Jónsdóttir, Á. H., Sigurjónsdóttir, H. Á., Thorsteinsdóttir, S., Long, T. E., Sverrisdóttir, I. S., Eyþórsson, E. S., Óskarsson, J. Þ., Pálsson, R., Indridason, Ó. S., Viðarsson, B., et al. (2024) · Blood · doi:10.1182/blood.2024025624 · Cited by 3
Monoklonale Gammopathie unklarer Signifikanz – ein häufiger Nebenbefund
Schieferdecker, A., Binder, M., Weisel, K. C., & Bokemeyer, C. (2019) · DMW - Deutsche Medizinische Wochenschrift · doi:10.1055/a-0832-3393 · Cited by 3
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BackgroundLokale und systemische Leichtkettenamyloidosen bei Patienten mit rheumatologischen Erkrankungen
Veelken, K., Hegenbart, U., Schönland, S. O., & Blank, N. (2020) · Zeitschrift für Rheumatologie · doi:10.1007/s00393-020-00848-6 · Cited by 3
Kreutzer, E. P., Sauer, S., Kriegsmann, M., Staemmler, H., Egerer, G., & Kriegsmann, K. (2021) · Cancers · doi:10.3390/cancers13184508 · Cited by 3
“≥70 years, MGUS is of particular clinical interest [3].”
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“MGUS progresses to multiple myeloma (MM) at a rate of 1% per year [1], but can also progress to light chain amyloidosis (AL amyloidosis), Waldenström macroglobulinemia, and lymphoma.”
BackgroundSelf-citationTherapie des multiplen Myeloms
Peest, D., Ganser, A., & Einsele, H. (2013) · Der Internist · doi:10.1007/s00108-013-3323-7 · Cited by 3
Pulmonary masses in a patient with dyspnea: Apply Occam's razor or Hickam's dictum?
Leung, N., Grogan, M. A., Johnson, G. B., Klecka, M. E., & Dispenzeiri, A. (2014) · American Journal of Hematology · doi:10.1002/ajh.23870 · Cited by 3
Large granular lymphocytic leukaemia
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Self-citationUpdate on the Diagnosis and Classification of the Plasma Cell Neoplasms
Lorsbach, R. B. (2010) · Surgical pathology clinics · doi:10.1016/j.path.2010.09.005 · Cited by 3
Immunostaining of skin biopsy adds no diagnostic value in MGUS-associated peripheral neuropathy
Al‐Zuhairy, A., Schrøder, H. D., Plesner, T., Abildgaard, N., & Sindrup, S. H. (2014) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2014.12.026 · Cited by 3
“MGUS is the most common monoclonal gammopathy [1–3].”
BackgroundSurvival of cancer patients with prior monoclonal gammopathy of undetermined significance
Gregersen, H., Sørensen, H. T., Engebjerg, M. C., Jensen, P., Severinsen, M. T., & Nørgaard, M. (2010) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2010.08.010 · Cited by 3
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“Almost 9% of males hat are 85 years of age and older have MGUS.2 Patients who have small monoclonal proteins without evidence of multiple myeloma (MM) were considered to have benign monoclonal gammopathy3 until a 1978 landmark study showed that these individuals showed an increased risk for progression to malignant B-…”
BackgroundInfluentialSun, Y., Sandhu, A., Gabaldon, D., Danaraj, J. J., Servilla, K. S., & Tzamaloukas, A. H. (2012) · Case Reports in Nephrology · doi:10.1155/2012/573650 · Cited by 3
Recent Advances in Antimultiple Myeloma Drug Development
Wang, N., Bartlow, P., Ouyang, Q., & Xie, X. (2014) · Pharmaceutical Patent Analyst · doi:10.4155/ppa.14.18 · Cited by 3
Immunological evidence of monoclonal gammopathy in North India: a hospital based study
Arora, S. (2010) · Pathology and Laboratory Medicine International · doi:10.2147/plmi.s10842 · Cited by 3
“5% in those over 70 years.(6) Geographical variation tends to exist with monoclonal gammopathies.”
Cinquanta, L., Tani, M., Sorrentino, M. C., Simula, M. P., Mangraviti, S., Milanesi, B., & Brusca, I. (2016) · La Rivista Italiana della Medicina di Laboratorio - Italian Journal of Laboratory Medicine · doi:10.1007/s13631-016-0130-x · Cited by 3
“I criteri per la definizione di MGUS prevedono per le classi IgG e IgA la presenza di una componente monoclonale <3,0 g/dl, una percentuale di plasmacellule midollari inferiore al 10% e l’assenza clinica di segni o sintomi riconducibile al mieloma quali l’ipercalcemia, l’insufficienza renale, l’anemia e la presenza di…”
Autoimmune peripheral neuropathies
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“The origin and pathophysiological significance of this monoclonal gammoglobin peak is unknown but may be interpreted as a parathymic syndrome, or an associated MGUS, which occurs in 3% of general population older than 50 years.(13) Few or absent B cells (87% of patients) may explain the lack in γ-globulin synthesis.”
Differential privacy for survival analysis and user data collection
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“• The FL chain dataset (FL) - It is obtained from a study on the association of the serum free light chain with higher death rates [69, 30].”
BackgroundThe caloric restriction fallacy, rodent diet aids and the tumor suppression theory of agingPreprint
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“In contrast, population-based studies from Europe and North America typically report MGUS prevalences of around 3%–6% among adults aged ≥ 50 years, while MM remains much less common [62, 63].”
InfluentialCassez, R., Cortet, B., Bouvard, B., Theis, D., Potey, C., Manier, S., Paccou, J., & Philippoteaux, C. (2026) · Archives of Osteoporosis · doi:10.1007/s11657-026-01693-x · Cited by 2
“…fracture risk and comparable to MGUS cohorts, such as that of Kyle et al., which shows that the prevalence of MGUS increases with age, suggesting that the mean age of affected patients is around 70 (21,463 individuals from Minnesota in the USA underwent SPE, identifying 694 cases of MGUS) [11].”
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Marcadores pronósticos en pacientes con gammapatía monoclonal de significado incierto
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“2% [34] and could therefore only account for Fig.”
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“However, it is important to accurately characterize MGUS lesions, since 1–2% of patients with MGUS progress to MM each year [4,5].”
BackgroundMonoclonal gammopathy detection and current technologies
Hutcherson, S. M., & Thoren, K. L. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-824302-2.00005-9 · Cited by 2
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Hematologic Disorders and the Nervous System
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“Furthermore, this increased risk of MGUS was only observed for prior cancers less than a year before screening and because MGUS is often present for decades 2,3 without progressing, it is unlikely that this is a causative association.”
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“We apply VIBNSurv to four real-world datasets SUPPORT (Study to understand prognoses and preferences for outcomes and risks of treatment) [42], GBSG [43], FLCHAIN (Assay of Serum Free Light Chain) [44], and multi-omics data from The Cancer Genome Atlas Low Grade Glioma (TCGA-LGG) [45].”
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Torka, P., Grover, N. S., Voorhees, T. J., Karmali, R., Annunzio, K., Watkins, M. P., Guzman, A. A., Reves, H., Tavakkoli, M., Christian, B. A., et al. (2025) · Hematological Oncology · doi:10.1002/hon.70087 · Cited by 2
“This is not surprising since monoclonal gammopathy of undetermined significance (MGUS) increases in incidence with age [20].”
SurvFormer: A Transformer Based Framework for Survival Analysis in Insurance Underwriting
Li, Y., Zhang, X., Hu, J., Xia, W., Liu, Z., Qin, X., Fei, B., & Zhou, J. (2025) · International World Wide Web Conference (WWW) · doi:10.1145/3701716.3715262 · Cited by 2
Monoclonal Gammopathy in ANCA-Negative Pauci-Immune Crescentic GN
Vargas-Brochero, M. J., Buglioni, A., Mekraksakit, P., Thongprayoon, C., Inácio, A. D. S., Domingues, P. A. D. C., Fervenza, F. C., & Zand, L. (2025) · Kidney360 · doi:10.34067/kid.0000000902 · Cited by 2
Bashall, S., Thomas, B., Sim, V., Wain, M., Child, F. J., Whittaker, S. J., & Morris, S. L. (2025) · British Journal of Dermatology · doi:10.1093/bjd/ljaf338 · Cited by 2
Cantley, M. D., Trainor, L. J., Cheney, E. A.-J., Watt, S. M., & Vandyke, K. (2025) · Pathology · doi:10.1016/j.pathol.2025.11.002 · Cited by 3
Batt, T. J., Tegg, E. M., & Johnston, A. M. (2016) · Pathology · doi:10.1016/j.pathol.2016.07.006 · Cited by 2
Hultcrantz, M. L., & Usmani, S. Z. (2022) · The Hematologist · doi:10.1182/hem.v19.1.202217 · Cited by 2
Epidemiology of Multiple Myeloma
Langston, A. A., & Francis, D. (2008) · Humana Press eBooks · doi:10.1007/978-1-59745-564-0_2 · Cited by 2
Zangari, M., Zhan, F., & Tricot, G. J. K. (2010) · Current Opinion in Supportive and Palliative Care · doi:10.1097/spc.0b013e32833d3011 · Cited by 2
A case of monoclonal gammopathy of undetermined significance (MGUS): type IgD-lambda
Galeazzi, M., Frezzotti, A., Paladini, C., Leoni, P., & Tocchini, M. (2013) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2012-0687 · Cited by 2
Coexistence of Charcot‐Marie‐Tooth disease type 1A and anti‐MAG neuropathy
Piscosquito, G., Salsano, E., Ciano, C., Palamara, L., Morbin, M., & Pareyson, D. (2013) · Journal of the Peripheral Nervous System · doi:10.1111/jns5.12029 · Cited by 2
García‐Castillo, H., Leal‐Ugarte, E., Ortiz‐Lazareno, P. C., Barrera‐Chairez, E., Rosales-García, V. H., & Barros‐Núñez, P. (2014) · Medical Oncology · doi:10.1007/s12032-014-0900-0 · Cited by 2
“6 % in individuals aged [80 years [5].”
BackgroundCharacterization of monoclonal gammopathy in patients with amyotrophic lateral sclerosis
Wolf, H., Posa, A., Panitz, S., Kornhuber, M. E., & Hanisch, F. (2015) · Acta Neurologica Scandinavica · doi:10.1111/ane.12377 · Cited by 2
“Comparable prevalences have been reported in octogenarians and non-agenarians (6, 12).”
BackgroundBiclonal Gammopathy in a Patient taking Efalizumab for the Treatment of Psoriasis
Fthenakis, A. (2013) · Journal of Hematology & Thromboembolic Diseases · doi:10.4172/2329-8790.1000106 · Cited by 2
“3% of those ≥ 70 according to a large epidemiological study in Olmsted County, Minnesota [9].”
BackgroundInfluentialPojero, F., Casuccio, A., Bassiano, F. D., Gervasi, F., Romano, G. C., & Caruso, C. (2015) · Immunity & Ageing · doi:10.1186/s12979-015-0032-1 · Cited by 2
“MM is usually preceded by a premalignant PC proliferative stage characterized by asymptomatic M-protein production known as monoclonal gammopathy of undetermined significance (MGUS), which is associated with a rate of progression to multiple myeloma of 1 % per year [4, 5].”
BackgroundSumekar, T. A., Ashrani, A. A., Winarni, T. I., & Hagerman, R. J. (2011) · Case Reports in Genetics · doi:10.1155/2011/143132 · Cited by 2
“It is an age-related medical condition found predominantly in older persons [15].”
BackgroundGalanakis, D. K., Spitzer, E. D., Perrotta, P. L., Nagaswami, C., Marchi, R. C., Spitzer, S. G., Refailovich, M., Smith, R. E., Zhang, L., Marmorat, C., et al. (2016) · Blood Coagulation & Fibrinolysis · doi:10.1097/mbc.0000000000000533 · Cited by 2
Short-term outcome and quality of life in kidney transplant recipient with monoclonal gammopathy
Yanishi, M., Tsukaguchi, H., Yoshida, T., Taniguchi, H., Yoshida, K., Mishima, T., Komai, Y., Yasuda, K., Watanabe, M., Sugi, M., et al. (2016) · CEN Case Reports · doi:10.1007/s13730-016-0218-1 · Cited by 2
Etiologia i patogeneza szpiczaka plazmocytowego
Iskierka‐Jazdzewska, E., & Jamroziak, K. (2015) · Hematologia · doi:10.5603/hem.2015.0037 · Cited by 1
FACULTE MIXTE DE MEDECINE ET DE PHARMACIE DE ROUEN
Eltchaninoff, H., Lacroix, D., & Savoure, D. A. (2013) · Cited by 2
Immunoglobulin and MYC Rearrangements in Multiple Myeloma Pathogenesis
Bergsagel, P. L., & Kuehl, W. M. (2015) · Springer eBooks · doi:10.1007/978-3-319-19983-2_8 · Cited by 2
Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma
Kastritis, E., & Dimopoulos, M. A. (2013) · Cambridge University Press eBooks · doi:10.1017/cbo9780511862465.010 · Cited by 2
Li, J., Wen, L., Tang, J., Zhang, H., Zhou, Z., Zhang, Y., Chen, Y., Chen, S., Wang, Q., Shao, J., et al. (2016) · Acta Haematologica · doi:10.1159/000450881 · Cited by 2
Monoclonal Gammopathy of Undetermined Significance
Patricia, M., Álvarez, R., Maldonado, J., Vinet, R., & Barri, K. (2013) · InTech eBooks · doi:10.5772/56138 · Cited by 2
Zakharova, E., Stolyarevich, E. S., Vorobyeva, O. A., & Nikitin, E. A. (2017) · Integrative Cancer Science and Therapeutics · doi:10.15761/icst.1000225 · Cited by 2
“MM is consistently preceded by precursor states of MGUS and SMM, these represent a continuum of progression of the tumor burden from the absence of symptoms or signs of end-organ damage towards full-blown symptomatic disease [1-8].”
BackgroundPrivacy-Preserving Mechanisms for Parametric Survival Analysis with Weibull Distribution
Nguyen, T. T., & Hui, S. C. (2017) · IEEE International Conference on Trust, Security and Privacy in Computing and Communications (TrustCom) · doi:10.1109/trustcom/bigdatase/icess.2017.271 · Cited by 2
Plasma cell neoplasms in HIV-Infected Patients: A Literature Review and Case Series
Leigton, R. A., Pivnik, A. V., Sergeeva, E. P., Kremneva, N. V., & Мухин, О. В. (2017) · Clinical oncohematology · doi:10.21320/2500-2139-2017-10-4-464-470 · Cited by 2
“У ВИЧ-инфицированных пациентов MGUS определяется в 3,8–26 % случаев в возрасте 34–43 лет [8], в общей популяции — в 3,2 % случаев в возрасте 70 лет и старше [9].”
Severe mononeuritis multiplex after rituximab in IgM‐κ monoclonal gammopathy
Lizarraga, A., Lizárraga, K. J., Hoffman, J. E., Ascherman, D. P., Shebert, R. T., & Verma, A. K. (2017) · Muscle & Nerve · doi:10.1002/mus.26005 · Cited by 2
“5% of the elderly population.(1,2) Immunoglobulin M (IgM)-MGUS may evolve into the B-cell malignancy Waldenstr€ om macroglobulinemia (WM), potentially requiring more aggressive treatment.”
BackgroundRodríguez, A. J. G., Bella-Navarro, R., Quiles, D. R., & Jordá-Cuevas, E. (2014) · Dermatology Online Journal · doi:10.5070/d3205022611 · Cited by 2
Léger, J., Chassande, B., Bombelli, F., Viala, K., Musset, L., & Neil, J. (2009) · Bulletin de l Académie Nationale de Médecine · doi:10.1016/s0001-4079(19)32500-2 · Cited by 2
Reisin, R. C., Salutto, V., Aguirre, F., Alvarez, V., Barroso, F. A., Bendersky, M., Berardo, A., Bettini, M., Borrelli, M. M., Chaves, M., et al. (2020) · Neurología Argentina · doi:10.1016/j.neuarg.2020.01.004 · Cited by 2
Devesa, A., Olleros, C. R., Kaçi, X., Askari, E., Blasco, A. C., Lázaro, A. M. P., Talavera, S. G., Octavio, J. G., Lapeña, G., Navarro, F., et al. (2020) · Cardiology Journal · doi:10.5603/cj.a2020.0059 · Cited by 2
“22% among individuals ≥ 60 years of age in the general population [8].”
BackgroundInfluentialMonoclonal gammopathies of undetermined significance and smoldering myeloma
Jurczyszyn, A. J., Hutch, R., Waszczuk‐Gajda, A., Suska, A., Krzanowska, K., & Vesole, D. H. (2020) · Acta Haematologica Polonica · doi:10.2478/ahp-2020-0035 · Cited by 2
Pyoderma gangrenosum with plasma cell dyscrasia should be subject for anti‐myeloma treatment
Nahi, H., Afram, G., Brauner, H., Talme, T., & Kuzmina, N. (2021) · International Journal of Dermatology · doi:10.1111/ijd.15504 · Cited by 2
The Value of Nerve Biopsy in Transthyretin Amyloidosis with Competing Comorbidities
Mak, G., Chum, M., & Lu, J. (2021) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/cjn.2021.175 · Cited by 2
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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