Direct evidence for a polygenic etiology in familial multiple myeloma
Open accessAbstract
Key Points: Although common risk alleles for multiple myeloma have been identified, their contribution to familial MM is unknown. We demonstrate an enrichment of common MM risk alleles in familial cases, providing the first direct evidence for a polygenic contribution.
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Studies report sporadic genetic events in families with a history of multiple myeloma.
“The first includes studies reporting sporadic genetic events in families with a history of MM.51,52”
From Evolution of Multiple Myeloma from a Genomic Perspective (2026) · cites this paper as [51]
The Results (p. 621) report an enrichment of common multiple-myeloma risk alleles in familial cases compared with sporadic cases. The discussion (p. 621) raises rare mutations only as a possible cause in other familial cases; it does not report sporadic genetic events in those families. (LLM, conf=0.82)
Experimental — accuracy not yet measuredThere exist families in which multiple myeloma and MGUS/SMM are clearly enriched.
“While occasional, these studies highlighted the existence of families in which MM and MGUS/SMM are clearly enriched.”
From Evolution of Multiple Myeloma from a Genomic Perspective (2026) · cites this paper as [51]
The Introduction reports families with multiple MM cases, and Materials and methods identifies patients with relatives who also had MM. The paper mentions MGUS as an MM precursor, but does not establish that MGUS or SMM is enriched in those families; it notes on p. 621 that the Swedish registries did not record MGUS cases. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThere is a fraction of individuals with a genetic predisposition to develop multiple myeloma.
“Finally, the idea that there is a fraction of individuals with a genetic predisposition to develop MM is further supported by two additional lines of evidence.”
From Evolution of Multiple Myeloma from a Genomic Perspective (2026) · cites this paper as [51]
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Cites
Genome-wide association analysis identifies 13 new risk loci for schizophrenia
Multicenter Genetic Studies of Schizophrenia Consortium, Ripke, S., Psychosis Endophenotypes International Consortium, Wellcome Trust Case Control Consortium 2, O'Dushlaine, C., Chambert, K., Moran, J. L., Kähler, A. K., Akterin, S., Bergen, S. E., et al. (2013) · Nature Genetics · doi:10.1038/ng.2742 · Cited by 1,496 · see citing works
Prevalence of monoclonal gammopathy of undetermined significance
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. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa054494 · Cited by 1,423 · cited 1× · see citing works
“It is preceded bymonoclonal gammopathy of unknown significance (MGUS),(2,3) a common condition (3% of$ 50-year-olds) defined as a clonal growth of plasma cells that does not satisfy the criteria for MM, but progresses to MM at a rate of about 1% per year.(4,5) Since the 1920s, several authors have reported families wi…”
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Research works printed but not linked: 16
- [1]1. Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15(12):e538-e548.
- [2]2. Landgren O, Kyle RA, Pfeiffer RM, et al. Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study. Blood. 2009;113(22):5412-5417.
- [3]3. Weiss BM, Abadie J, Verma P, Howard RS, Kuehl WM. A monoclonal gammopathy precedes multiple myeloma in most patients. Blood. 2009;113(22): 5418-5422.
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- [12]12. Ogmundsdóttir HM, Haraldsdóttirm V, Jóhannesson GM, et al. Familiality of benign and malignant paraproteinemias. A population-based cancer-registry study of multiple myeloma families. Haematologica. 2005;90(1):66-71.
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- [16]16. Broderick P, Chubb D, Johnson DC, et al. Common variation at 3p22.1 and 7p15.3 influences multiple myeloma risk. Nat Genet. 2011;44(1):58-61.
- [17]17. Chubb D, Weinhold N, Broderick P, et al. Common variation at 3q26.2, 6p21.33, 17p11.2 and 22q13.1 influences multiple myeloma risk. Nat Genet. 2013;45(10):1221-1225.
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Evolution of Multiple Myeloma from a Genomic Perspective
Maura, F., Samur, M., & Munshi, N. (2026) · Blood · doi:10.1182/blood.2024026313 · Cited by 8 · see citing works
- Authors
- Halvarsson, B.-M., Wihlborg, A.-K., Ali, M., Lemonakis, K., Johnsson, E., Niroula, A., Cibulskis, C., Weinhold, N., Försti, A., Alici, E., Langer, C., Pfreundschuh, M., Goldschmidt, H., Mellqvist, U.-H., Turesson, I., Waage, A., Hemminki, K., Golub, T., Nahi, H., Gullberg, U., Hansson, M., & Nilsson, B.
- Affiliations
- Lund University (SE)
- Broad Institute (US)
- Heidelberg University (DE)
- German Cancer Research Center (DE)
- Karolinska Institutet (SE)
- Universität Ulm (DE)
- Saarland University (DE)
- Sahlgrenska University Hospital (SE)
- Norwegian University of Science and Technology (NO)
- Corresponding author
- Hansson, Markus
- Nilsson, Björn
- ORCID
- Venue
- Blood Advances
- Publisher
- American Society of Hematology
- Published
- 2017-04-07
- Volume
- 1
- Issue
- 10
- Pages
- 619-623
- ISSN
- 2473-9529 (ISSN-L)
- 2473-9537
- PMC
- PMC5728350
- OpenAlex
- W2605155192
- Cited by
- 21
- References
- 2
- Citations by year
- 2025: 3 · 2024: 3 · 2023: 1 · 2022: 1 · 2021: 4 · 2020: 2 · 2019: 2 · 2018: 5
- FWCI
- 1.90
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Blood Advances (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Keywords
- multiple myeloma, heritability, genetic enrichment, mixture models, hematologic malignancies, genetic risk factors
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