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Multiple myeloma gammopathies

Risk of MGUS in relatives of multiple myeloma cases by clinical and tumor characteristics


We and others have shown increased risk of monoclonal gammopathy of undetermined significance (MGUS) in first-degree relatives of patients with multiple myeloma (MM). Whether familial risk of MGUS differs by the MM proband’s age at onset, tumor or clinical characteristics is unknown. MM and smoldering MM (SMM) cases (N = 430) were recruited from the Mayo Clinic in Rochester, Minnesota between 2005–2015. First-degree relatives over age 40 provided serum samples for evaluation of MGUS (N = 1179). Age and sex specific rates of MGUS among first-degree relatives were compared to a population-based sample. Cytogenetic subtypes were classified by Fluorescence in situ hybridization. MGUS was detected in 75 first-degree relatives for an age- and sex- adjusted prevalence of 5.8% (95% CI: 4.5–7.2). Prevalence of MGUS in first-degree relatives was 2.4 fold (95% CI: 1.9–2.9) greater than expected rates. Familial risk did not differ by proband’s age at diagnosis, gender, isotype, IgH translocation, or trisomy. This study confirms first-degree relatives of MM cases have a significantly higher risk of MGUS compared to the general population, regardless of age, gender, or tumor characteristics. In selected situations, such as multiple affected first-degree relatives, screening of first-degree relatives of MM cases could be considered for follow-up and prevention strategies.

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We would especially like to acknowledge the many MM/SMM patients and their families who contributed to this research. This work was supported in part by grants R01 CA107476, R01 CA168762, R25 CA092049, and P50 CA186781 (Mayo Clinic Myeloma SPORE) from the National Cancer Institute of the National Institutes of Health and the Mayo Clinic Cancer Center.

Authors' contributions

AICG wrote, reviewed, and edited the original draft, and visualized the tables/figures. SK and SVR helped with conceptualization, methodology, contributed with patients’ samples, provided funding for study, and reviewed/edited. AR helped with data abstraction and reviewed/edited. RAK defined MGUS in first-degree relatives, helped with study methodology, and reviewed/edited. JAK defined MGUS in first-degree relatives and reviewed/edited. DLM contributed to FISH methodology and reviewed/edited. ADN provided project management and reviewed/edited. AJG reviewed/edited. DRL and MMO’B performed statistical analyses and helped with methodology, reviewed/edited, and contributed to visualization of tables/figures. SLS helped with conceptualization and methodology, contributed with patients’ samples, provided funding for the study, reviewed/edited, and supervised research and data analysis. CMV helped with conceptualization and study methodology, defined statistical analytic approach, contributed with patients’ samples, provided funding for the study, reviewed/edited, visualized the tables/figures, and supervised research and data analysis.

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The authors declare that they have no conflict of interest.

Correspondence to Celine M. Vachon.

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