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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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“In addition, as MGUS is present in about 3 % of people greater than age 50 years [1], it is almost certainly underrepresented in this database.”
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“IgM MGUS represents only 15 to 17% of all MGUS cases 10,11 .”
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“MGUS is present in 3% of people over 50 years and in up to 5% of people over 70 years.(3,4) Patients with MGUS have a twofold increased risk of developing any infection at 5- and 10-year follow-up.”
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ResultBlood donor eligibility criteria for medical conditions: A BEST collaborative study
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“Although IgG is the most common paraprotein (~5970%), followed by IgM (~17%) and IgA (~11-17%) (19,20).”
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“5% in the general adult population >50 years; its incidence increases with age (being >5% in patients aged >70 years).([3])”
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“These findings are also consistent with previous reports.(9,11) In previous studies, although IgG was the most common M-protein found in the general population, the most common paraprotein detected in association with paraproteinemic neuropathies was IgM, usually along with the kappa light chain.”
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“The classical definitions of Mspike-MGUS and light-chain-MGUS used in previous FDNY and Olmsted County prevalence studies were applied [16, 17, 23].”
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“Recent studies have shown how MGUS can be found in about 5% of the population above the age of 40 [3], with a prevalence increasing with age and a rate of progression from MGUS to MM of approximately 1% of patients per year [4].”
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“3% in persons of 70 years or older [4].”
BackgroundExtraosseous multiple myeloma: imaging spectrum in the abdomen and pelvis
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“MGUS is the most common type of plasma cell dyscrasia and is seen in more than 3% of the general population aged 50 years or older [4].”
BackgroundFalsely markedly elevated 25-hydroxyvitamin D in patients with monoclonal gammopathies
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“study among residents of Olmsted County, Minnesota [19].”
BackgroundInfluentialCardiac amyloidosis: an update on diagnosis, current therapy, and future directions
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Monoclonal gammopathy in a tertiary referral hospital
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Familial Multiple Myeloma: Report on Two Families and Discussion of Screening Options
Gerkes, E. H., de Jong, M. M., Sijmons, R. H., & Vellenga, E. (2007) · Hereditary Cancer in Clinical Practice · doi:10.1186/1897-4287-5-2-72 · Cited by 9
“MGUS progresses into MM in about 1% of cases per year and progression cannot be prevented [27-28].”
BackgroundSmith, J. D., Raines, G., & Schneider, H. G. (2015) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2015-0806 · Cited by 9
Strategy for Detecting and Following Monoclonal Gammopathies
Katzmann, J. A., & Keren, D. F. (2016) · ASM Press eBooks · doi:10.1128/9781555818722.ch11 · Cited by 9
Self-citationAsymmetric Deep Stromal Keratopathy in a Patient With Multiple Myeloma
Tainsh, L. T., Coady, P. A., Sinard, J. H., Neparidze, N., Meskin, S. W., Adelman, R. A., & Chow, J. (2017) · Cornea · doi:10.1097/ico.0000000000001139 · Cited by 9
Plasma cell diseases and organ transplant: A comprehensive review
Cowan, A. J., Johnson, C. K., & Libby, E. N. (2018) · American Journal of Transplantation · doi:10.1111/ajt.14731 · Cited by 9
John, K., Mishra, A. K., & Iyyadurai, R. (2019) · European Heart Journal - Case Reports · doi:10.1093/ehjcr/ytz162 · Cited by 9
“5% of the population above 50 years of age.(9) Hence ATTR amyloidosis with co-existent MGUS is the most likely diagnosis in our patient.”
BackgroundDistinctive patterns of peripheral neuropathy across the spectrum of plasma cell disorders
Byun, J. M., Kwon, Y. N., Koh, Y., Yoon, S., Sung, J., & Kim, I. (2019) · Scientific Reports · doi:10.1038/s41598-019-53289-w · Cited by 9
An update to the pathogenesis for monoclonal gammopathy of renal significance
Zuo, C., Zhu, Y., & Xu, G. (2020) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2020.102926 · Cited by 9
Diagnostic evaluation of monoclonal gammopathy of undetermined significance
Rajan, A. M., & Rajkumar, S. V. (2013) · European Journal Of Haematology · doi:10.1111/ejh.12198 · Cited by 9
“Monoclonal gammopathy of undetermined significance (MGUS) is a common premalignant plasma cell proliferative disorder present in over 3% of the general population 50 yrs and older (1, 2).”
BackgroundSelf-citationA tower of babel of acronyms? The shadowlands of MGUS/MBL/CHIP/TCUS
Bravo‐Pérez, C., & Gurnari, C. (2024) · Seminars in Hematology · doi:10.1053/j.seminhematol.2024.01.004 · Cited by 8
Moreno, D. F., Jiménez, C., Escalante, F., Askari, E., Castellanos‐Alonso, M., Arnao, M., Heredia, Á., Canales, M. Á., Alcalá, M., Bermúdez, A., et al. (2024) · HemaSphere · doi:10.1002/hem3.70029 · Cited by 8
“1 The spectrum of disease progression includes predominantly WM, followed by diffuse large B cell lymphoma (DLBCL), AL amyloidosis, chronic lymphocytic leukemia (CLL), and multiple myeloma (MM), among others.”
BackgroundKyrtsonis, M. C. (2010) · The Application of Clinical Genetics · doi:10.2147/tacg.s7456 · Cited by 8
Kidney Biopsy in Patients With Monoclonal Gammopathy: A Multicenter Retrospective Cohort Study
Nie, S., Wang, M., Wan, Q., Kong, Y., Ou, J., Jia, N., Zhang, X., Luo, F., Liu, X., Wang, L., et al. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.687149 · Cited by 8
Histological Findings in Kidney Biopsies of Patients with Monoclonal Gammopathy—Always a Surprise
Klank, D., Hoffmann, M. F., Porubský, Š., & Bergner, R. (2022) · Diagnostics · doi:10.3390/diagnostics12081912 · Cited by 8
“5% among those 85 years of age or older [3].”
BackgroundPérez‐Escurza, O., Flores-Montero, J. A., Óskarsson, J. Þ., Sanoja-Flores, L., Pozo, J., Lécrevisse, Q., Martín, S., Reed, E. R., Hákonardóttir, G. K., Harding, S. J., et al. (2023) · Blood Cancer Journal · doi:10.1038/s41408-023-00944-1 · Cited by 12
Emery, A., Moore, S. E., Crowe, J., Murray, J., Peacock, O., Thompson, D., Betts, F., Rapps, S., Ross, L., Rothschild-Rodriguez, D., et al. (2024) · BMC Cancer · doi:10.1186/s12885-024-11817-6 · Cited by 9
“The patient was aged 44 years– which is relatively young in the context of MGUS and SMM [3]– and was a former elite handball athlete with a 20-year training history at high volumes ( > 30 h/week) prior to diagnosis of SMM [9].”
BackgroundDNA vaccines against GPRC5D synergize with PD-1 blockade to treat multiple myeloma
Neeli, P. K., Maza, P. A. M., Chai, D., Zhao, D., Hoi, X. P., Chan, K. S., Young, K. H., & Li, Y. (2024) · npj Vaccines · doi:10.1038/s41541-024-00979-w · Cited by 9
Vermorken, A. J. M., Zhu, J., de Ven, W. J. M. V., Cui, Y., & Fryns, J. P. (2010) · Experimental and Therapeutic Medicine · doi:10.3892/etm_00000041 · Cited by 8
“The prevalence gradually increases from 1.7% in individuals between 50 and 59 years to 6.6% in individuals above 80 years of age (6).”
InfluentialMonoclonal B cell lymphocytosis: Clinical and population perspectives
Caporaso, N. E., Marti, G. E., Landgren, O., Azzato, E. M., Weinberg, J. B., Goldin, L. R., & Shanafelt, T. D. (2010) · Cytometry Part B Clinical Cytometry · doi:10.1002/cyto.b.20555 · Cited by 8
“(MM) as a B-cell precursor (18); The etiologic origin of MBL is a mystery.”
BackgroundRoof, L., Coker, W. J., Lazarchick, J. J., & Kang, Y. (2014) · PubMed · Cited by 8
Campbell, J. P., Heaney, J. L. J., Pandya, S., Afzal, Z., Kaiser, M., Owen, R. G., Child, J. A., Cairns, D. A., Gregory, W. M., Morgan, G. J., et al. (2017) · The Lancet Haematology · doi:10.1016/s2352-3026(17)30209-0 · Cited by 8
“In one patient, the MGUS MAB progressed to MM; this is broadly in line with known rates of MGUS progression over a one year period in persons of this age (6).”
BackgroundResultSfeir, J. G., Guzman, T. D. P., Bedatsova, L., Broski, S. M., & Drake, M. T. (2020) · Bone · doi:10.1016/j.bone.2020.115394 · Cited by 8
Gran, C., Liwing, J., Wagner, A. K., Verhoek, A., Gezin, A., Alici, E., & Nahi, H. (2020) · American Journal of Hematology · doi:10.1002/ajh.25999 · Cited by 8
Abell, K. B., Chadwell, S. E., Burrow, T. A., Becker, A. P. P., Bailey, L. A., Steele, P. E., Zhang, X., Islas‐Ohlmayer, M., Bittencourt, R., Schwartz, I. V. D., et al. (2020) · American Journal of Medical Genetics Part C Seminars in Medical Genetics · doi:10.1002/ajmg.c.31870 · Cited by 8
“In the general population, the prevalence of MGUS is 2–3 % of adults over 50 years-old with median age of 70 years (Kyle et al., 2006), and the median age for MM is 66 years old (Anderson, 2003).”
BackgroundVasco-Mogorrón, M. A., Campillo, J. A., Periago, A., Cabañas, V., Berenguer, M., García-Garay, M. C., Gimeno, L., Soto‐Ramírez, M. F., Martínez-Hernández, M. D., Muro, M., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22083895 · Cited by 8
“Plasma cell neoplasms with a prevalence >3% on population aged ≥ 50 (>5% on aged > 70) for MGUS [9,10] and close to 1% for MM are one of the most common pathologies in hematology clinics worldwide.”
BackgroundAutoimmune Peripheral Neuropathies
Dalakas, M. C. (2019) · Elsevier eBooks · doi:10.1016/b978-0-7020-6896-6.00067-3 · Cited by 8
Alreshq, R. S., Cozzolino, M. J., Lilleness, B., Pipilas, A. R., Mendelson, L. M., Joshi, T., Muralidhar, V., Guardino, E. T., Berk, J. L., Siddiqi, O. K., et al. (2022) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2022.06.064 · Cited by 8
Prevalence of MGCS Among Patients With Monoclonal Gammopathies
Theodorakakou, F., Fotiou, D., Gavriatopoulou, M., Ntanasis‐Stathopoulos, I., Spiliopoulou, V., Malandrakis, P., Migkou, M., Eleutherakis‐Papaiakovou, E., Kanellias, N., Terpos, E., et al. (2023) · HemaSphere · doi:10.1097/hs9.0000000000000908 · Cited by 8
Monoclonal Gammopathy and Smoldering Multiple Myeloma: Diagnosis, Staging, Prognosis, Management
Hillengaß, J., Moehler, T. M., & Hundemer, M. (2011) · Recent results in cancer research/Recent Results in Cancer Research · doi:10.1007/978-3-540-85772-3_6 · Cited by 8
“5% in those 85 years and older, respectively with a preference of men (Kyle et al. 2006).”
BackgroundGalioto, A., Morando, F., Rosi, S., Schipilliti, M., Fasolato, S., Magrin, M., Frigo, A. C., Adami, F., Cavallin, M., Zanus, G., et al. (2011) · Transplant International · doi:10.1111/j.1432-2277.2011.01362.x · Cited by 8
“3% in those over 70, the prevalence being higher in men than in women [2].”
Background
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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