Risk of multiple myeloma and monoclonal gammopathy of undetermined significance among white and black male United States veterans with prior autoimmune, infectious, inflammatory, and allergic disorders

Brown, Linda Morris; Gridley, Gloria; Check, David P.; Landgren, Ola

doi:10.1182/blood-2007-10-121285

Cited by 204 publications

(186 citation statements)

References 44 publications

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“…Recently, a nationwide study based on 4 million US veterans found immunerelated conditions to be associated with the elevated risk of MGUS and MM. 29 Similar findings, based on the Scandinavian data, have also been reported. 23,30 From all the above, it is clear that further studies are needed to better define the role of genetics and environmental factors in the development of monoclonal gammopathies.…”

Section: Genesissupporting

confidence: 78%

“…In addition, there is recent evidence supporting a role for immune-mediated conditions in the etiology/progression of MGUS and MM. 23,29,30,49 In the case of the so-called 'evolving' MGUS (see the section 'Predictors of malignant transformation'), the mechanisms that limit the growth of the emerging plasma cell clone would not exist and, irrespective of the initial plasma cell mass, all these patients would eventually end up with a symptomatic monoclonal gammopathy. In fact, the authors of this review believe that evolving MGUS are slowly growing myelomas from the beginning, but this observation needs confirmation in other series.…”

Section: Mechanisms Of Progressionmentioning

confidence: 99%

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Pathogenesis and progression of monoclonal gammopathy of undetermined significance

et al. 2008

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In Caucasians, monoclonal gammopathy of undetermined significance (MGUS) is an age-related condition with prevalence as high as 3% in persons older than 50 years. Compared with whites, blacks have around two-and threefold higher prevalence rates of MGUS and multiple myeloma (MM), respectively. Risk of progression from MGUS to MM has been found to be very similar in whites and blacks. On average, the transformation rate to a malignant monoclonal gammopathy is 1% per year, with the mechanisms of progression likely related to bone marrow microenvironment and/or the cytokine network. Overall, the actuarial probability of progression at 25 years of follow-up is about 30%. However, when the competing causes of death are taken into account, the actual rate of progression is only 11%. The predictors of malignant transformation are the plasma cell mass (M-protein size and/or proportion of plasma cell in the bone marrow), IgA isotype, serum free light-chain ratio and 'evolving' type and ratio between phenotypically aberrant and normal bone marrow plasma cells. It is recommended to follow these patients, particularly those with high risk of progression, annually to detect MM before complications, such as renal failure or extensive skeletal, involvement occur. Leukemia ConceptThe term monoclonal gammopathy of undetermined significance (MGUS) indicates the presence of a monoclonal protein (M-protein) in individuals with no features of multiple myeloma (MM), Waldenströ m's macroglobulinemia, primary amyloidosis or other related disorders. 1 Patients with MGUS have a serum M-protein size lower than 3 g per 100 ml, and proportion of bone marrow plasma cells of less than 10%, with no clinical manifestations related to their monoclonal gammopathy (Table 1). 1,2 MGUS was initially considered to be a benign condition and was frequently named 'benign' or 'idiopathic' monoclonal gammopathy. 3,4 However, from the time of the pioneer observations in the Mayo Clinic (Rochester, MN, USA) series, this disorder could no longer be considered as 'benign' as a number of patients ultimately develop a malignant monoclonal gammopathy. 1,[5][6][7][8] For this reason, Dr Robert Kyle coined the term 'monoclonal gammopathy of undetermined significance'. 1,5 Considering that MGUS is usually an unexpected finding in a routine medical survey, or in the study of an unrelated disorder, not surprisingly, this condition is usually first seen by physicians working in many different fields of medical practice. In consequence, it is crucial to know the significance of the finding: whether it will require further investigation and whether it will remain stable or, by the contrary, will evolve into a symptomatic monoclonal gammopathy requiring therapeutic intervention. 9 EpidemiologyPrior studies based on Caucasians showed that the prevalence of MGUS increases with age. For many years, it was considered that the prevalence of MGUS was 1 and 3 % in persons older than 50 and 70 years, respectively. 10-14 However, in a recent study performed on residents of Olms...

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Section: Genesissupporting

confidence: 78%

Section: Mechanisms Of Progressionmentioning

confidence: 99%

Pathogenesis and progression of monoclonal gammopathy of undetermined significance

et al. 2008

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“…One possible explanation for this finding is a difference in the response to immune stimulation between the races as these are putative triggers for the development of MGUS/MM. 8,43,44 In addition, the differences between the study of African Americans compared with Ghanaians suggest the possibility of differing environmental exposures, such as infectious agents or toxins, which may result in differing the immune responses. In the Ghana study, the self-reported history of infections did not show any association with the development of MGUS.…”

Section: Other Clinical and Biological Racial Disparity Patternsmentioning

confidence: 99%

“…In fact, in a large study from the US Veteran's Affairs system, a history of autoimmune, infectious and inflammatory conditions were associated with an increased risk for MGUS and MM; risk seemed to be equal between the races. 44 Although gene-expression profiling and cytogenetic analysis in MM reveal evidence of heterogeneity reflected in markedly different clinical outcomes, [45][46][47] to our knowledge, no large studies have specifically addressed the molecular features of MM across ethnic groups. A few studies have compared survival patterns between African-American and Caucasian patients treated with both conventional therapy and autologous stem cell transplantation and have reported similar outcomes.…”

Section: Other Clinical and Biological Racial Disparity Patternsmentioning

confidence: 99%

Patterns of monoclonal gammopathy of undetermined significance and multiple myeloma in various ethnic/racial groups: support for genetic factors in pathogenesis

2009

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Monoclonal gammopathy of undetermined significance (MGUS) is one of the most common premalignant disorders in Western countries. Recent studies show that almost every multiple myeloma (MM) case is preceded by an MGUS stage. Interestingly, prevalence and incidence patterns for MGUS and MM show striking disparity patterns across ethnic/racial groups, most notably the two-to threefold increase in both these disorders in African Americans compared with Caucasians. In contrast, studies on Asian patients show lower prevalence/ incidence for MGUS/MM compared with Caucasians. Familial aggregation for both MGUS and MM has been observed; the risk for MGUS or MM in family members with these disorders is increased about two-to three fold compared with the general population. Although underlying mechanisms remain unclear, there is evidence of heterogeneity among MGUS patients from different ethnic/racial groups. For example, compared with Caucasians, African-American and African MGUS patients have reportedly lower rates of immunoglobulin M (IgM) MGUS (versus IgG/IgA MGUS) and higher rates of unquantifiable immunoglobulins (Igs). This review focuses on racial disparity and familial aggregation patterns for MGUS and MM and discusses how these observations provide novel clues with regard to pathogenesis.

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“…Prior studies have found a history of infectious disease to increase the risk of developing MGUS and MM suggesting that infections may trigger MGUS or MM in susceptible patients. 19,20 Furthermore, low levels of polyclonal immunoglobulins in MGUS patients have been found to be a risk factor for progression to MM or a related lymphoproliferative malignancy. 21 Taken together, the predisposing role of infections in MGUS and MM remains for the most part unclear.…”

Section: Mgus Patients Mgus Controlsmentioning

confidence: 99%

Monoclonal gammopathy of undetermined significance and risk of infections: a population-based study

Kristinsson¹,

Tang²,

Pfeiffer³

et al. 2011

Haematologica

122

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Risk of multiple myeloma and monoclonal gammopathy of undetermined significance among white and black male United States veterans with prior autoimmune, infectious, inflammatory, and allergic disorders

Cited by 204 publications

References 44 publications

Pathogenesis and progression of monoclonal gammopathy of undetermined significance

Pathogenesis and progression of monoclonal gammopathy of undetermined significance

Patterns of monoclonal gammopathy of undetermined significance and multiple myeloma in various ethnic/racial groups: support for genetic factors in pathogenesis

Monoclonal gammopathy of undetermined significance and risk of infections: a population-based study

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