Disease associations with monoclonal gammopathy of undetermined significance can only be evaluated using screened cohorts : results from the population-based iStopMM study

• Published in: Haematologica
• Main Authors: Sigurbergsdóttir, Aðalbjörg Ýr, Rögnvaldsson, Sæmundur, Thorsteinsdóttir, Sigrún, Sverrisdóttir, Ingigerður, Sigurðardóttir, Guðrún Ásta, Viðarsson, Brynjar, Önundarson, Páll Torfi, Agnarsson, Bjarni Agnar, Sigurðardóttir, Margrét, Þorsteinsdóttir, Ingunn, Ólafsson, Ísleifur, Þórðardóttir, Ásdís Rósa, Gíslason, Gauti Kjartan, Ólafsson, Andri, Hultcrantz, Malin, Durie, Brian G M, Harding, Stephen, Landgren, Ola, Löve, Þorvarður Jón, Kristinsson, Sigurður Yngvi
• Other Authors: Faculty of Medicine, Internal Medicine and Emergency Services, Other departments, Clinical Laboratory Services, Diagnostics and Blood Bank
• Format: Article in Journal/Newspaper
• Language: English
• Published: 2023
• Subjects: Blóðlæknisfræði; Meinafræði; Lífefna- og sameindalíffræði; Gigtarlæknisfræði; SDG 3 - Good Health and Well-being; Iceland
• Online Access: https://hdl.handle.net/20.500.11815/4645; https://doi.org/10.3324/haematol.2023.283191

Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic precursor condition that precedes multiple myeloma and related disorders but has also been associated with other medical conditions. Since systematic screening is not recommended, MGUS is typically diagnosed due to underlying diseases and most cases are not diagnosed. Most previous studies on MGUS disease associations have been based on clinical cohorts, possibly resulting in selection bias. Here we estimate this selection bias by comparing clinically diagnosed and screened individuals with MGUS with regards to demographics, laboratory features, and comorbidities. A total of 75,422 participants in the Iceland Screens, Treats, or Prevents Multiple Myeloma (iStopMM) study were screened for MGUS by serum protein electrophoresis, immunofixation and free light chain assay (clinicaltrials gov. Identifier: NCT03327597). We identified 3,352 individuals with MGUS, whereof 240 had previously been clinically diagnosed (clinical MGUS), and crosslinked our data with large, nationwide registries for information on comorbidities. Those with clinical MGUS were more likely to have at least one comorbidity (odds ratio=2.24; 95% confidence interval: 1.30-4.19), and on average had more comorbidities than the screened MGUS group (3.23 vs. 2.36, mean difference 0.68; 95% confidence interval: 0.46-0.90). They were also more likely to have rheumatological disease, neurological disease, chronic kidney disease, liver disease, heart failure, or endocrine disorders. These findings indicate that individuals with clinical MGUS have more comorbidities than the general MGUS population and that previous studies have been affected by significant selection bias. Our findings highlight the importance of screening data when studying biological and epidemiological implications of MGUS. Peer reviewed