scholarly journals Risk of monoclonal gammopathy of undetermined significance (MGUS) and subsequent multiple myeloma among African American and white veterans in the United States

Blood ◽  
2006 ◽  
Vol 107 (3) ◽  
pp. 904-906 ◽  
Author(s):  
Ola Landgren ◽  
Gloria Gridley ◽  
Ingemar Turesson ◽  
Neil E. Caporaso ◽  
Lynn R. Goldin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
African American ◽  
African Americans ◽  
Monoclonal Gammopathy ◽  
White Male ◽  
Cumulative Risk ◽  
Prevalence Ratio ◽  
The United States ◽  
Increased Risk ◽  
Undetermined Significance

Abstract The age-adjusted incidence of multiple myeloma (MM) is 2-fold higher in African Americans than in whites. A few small studies have reported a higher prevalence of monoclonal gammopathy of undetermined significance (MGUS) in African Americans versus whites. Etiologic factors for MGUS and determinants for transformation of MGUS to MM are unknown. We quantified the prevalence of MGUS and subsequent risk of MM among 4 million African American and white male veterans admitted to Veterans Affairs (VA) hospitals. The age-adjusted prevalence ratio of MGUS in African Americans compared with whites was 3.0 (2.7-3.3 95% confidence interval). Among 2046 MGUS cases, the estimated cumulative risk of MM during the first 10 years of follow-up was similar (P = .37) for African Americans (17%) and whites (15%). In the largest study to date, we suggest that the excess risk of MM in African Americans results from an increase in risk of MGUS rather than an increased risk of progression from MGUS to MM.

Risk of Monoclonal Gammopathy of Undetermined Significance (MGUS) and Subsequent Multiple Myeloma among African-American and White Veterans in the U.S.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1541-1541
Author(s):  
Ola Landgren ◽  
Gloria Gridley ◽  
Ingemar Turesson ◽  
Neil E. Caporaso ◽  
Lynn R. Goldin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
African American ◽  
African Americans ◽  
Monoclonal Gammopathy ◽  
Statistical Significance ◽  
Cox Proportional Hazards Model ◽  
Wilcoxon Test ◽  
Cumulative Probability ◽  
Increased Risk ◽  
Undetermined Significance

Abstract Background: The age-adjusted incidence of multiple myeloma (MM) is 2-fold higher in African-Americans than in Whites, which is paralleled by reports of a higher prevalence of monoclonal gammopathy of undetermined significance (MGUS) in African Americans. Etiological factors for MGUS and determinants for transformation of MGUS to MM are unknown, but data on the race-specific prevalence of MGUS and progression of MGUS to MM may provide clues to etiology. Objective: To determine the prevalence and the probability of progression from MGUS to MM in African-Americans compared to Whites. Patients and Methods: The cohort was identified from review of discharge diagnoses in hospital medical records for inpatient hospitalizations at 142 nationwide U.S. Veterans Affairs (VA) hospitals between October 1, 1980 and September 30, 1996. The target population for calculation of MGUS prevalence included all African-American (N=749,020) and White (N=3,248,795) veterans hospitalized at least once at age 18 or older. For estimating the risk of malignancy, all subjects without a prior discharge diagnosis of malignancy were followed from one year after index hospital discharge (MGUS diagnosis for MGUS cases, and first discharge for any reason for all others) until the diagnosis of a first malignancy, death, or the end of the observation period (September 30, 1996), whichever came first. Using the Kaplan-Meier procedure, we calculated the cumulative probability of developing MM among MGUS cases according to race, testing for statistical significance using the Wilcoxon-test appropriate for censored data. The Cox proportional hazards model was applied. Poisson regression was used for analyses comparing risk for MM among MGUS versus non-MGUS cohorts. Results: We identified 734 cases of MGUS in African-Americans and 1,312 in Whites. The age-adjusted prevalence-rate for MGUS was 3.0-fold (2.7–3.3 95% CI) higher in African-Americans than in Whites. Among MGUS cases, the estimated cumulative risk of developing MM during the first 10 years of follow-up was similar (Wilcoxon-test P=0.37) for African-Americans (17%) and for Whites (15%). The risk of developing MM among all MGUS (versus non-MGUS) cases was very high (RR=89.1; 74.7–106.3, 95%CI). Conclusions: In the largest study to date, we suggest that the excess risk of MM in African-Americans results from an increase in risk of MGUS rather than an increased risk of progression from MGUS to MM.

Obesity is Associated with a 2-Fold Elevated Risk of Monoclonal Gammopathy of Undetermined Significance (MGUS) Among African-American and Caucasian Women.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4876-4876
Author(s):  
Ola Landgren ◽  
Vincent Rajkumar ◽  
Ruth Pfeiffer ◽  
Robert Kyle ◽  
Jerry Katzmann ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
African American ◽  
African Americans ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Conflicts Of Interest ◽  
Pearson Correlation ◽  
Elevated Risk ◽  
Caucasian Women ◽  
Undetermined Significance

Abstract Abstract 4876 Background Recent studies have found obesity to be associated with a 1.5- to 2-fold elevated risk of developing multiple myeloma. This is of particular interest given that elevated levels of the pro-inflammatory cytokine interleukin (IL)-6 have been found in obese persons, and, at the same time, IL-6 has well-known proliferative and anti-apoptotic effects on monoclonal plasma-cells. Also insulin-like growth factors (IGFs) have been proposed to play a role since obesity often causes insulin resistance, which in turn modulates the bioavailability of IGF-1 Similar to IL-6, prior studies have found IGF-1 to have both growth and survival effects on monoclonal plasma-cells. Based on these facts, we have speculated that obesity might increase the risk of the multiple myeloma precursor monoclonal gammopathy of undetermined significance (MGUS), or, alternatively, that obesity may increase the risk for transformation from MGUS to multiple myeloma. We conducted the first large screening study designed to assess the association between obesity and MGUS among almost 2,000 African-American and Caucasian women. Methods We included 1000 African-American and 996 Caucasian women (age 40-79, median 48 years) from the Southern Community Cohort Study to assess MGUS risk in relation to obesity. Per our sampling strategy, about 50% of the participants were obese. Medical record-abstracted weight and height (measured on the day of study enrollment) and self-reported values had very high concordance (Pearson correlation >0.95). Serum samples from all subjects were analyzed by electrophoresis performed on agarose gel; samples with a discrete or localized band were subjected to immunofixation. Using logistic regression models, we estimated odds ratios (ORs) as measures of risk. Results Among all study participants, 39 (3.9%) African-Americans and 21 (2.1%) Caucasians were found to have MGUS, yielding a 1.9-fold (95%CI 1.1-2.3; p=0.021) higher risk of MGUS among African-Americans (vs. Caucasians). On multivariate analysis, we found obesity (OR=1.8, 95%CI 1.03-3.1; p=0.039), African-American race (OR=1.8, 95%CI 1.04-3.1; p=0.037), and increasing age (quartiles: ≥55 vs. <43 years) (OR=2.5, 95%CI 1.1-5.7; p=0.028) to be independently associated with an excess risk of MGUS. Another interesting finding was that the distribution of the monoclonal immunoglobulin isotype usage among African-American and Caucasian women was significantly different (p=0.007). Their respective rates were: IgG in 79.5% and 71.3 %; IgA in 7.7% and 0%; IgM in 7.7% and 19%; biclonal in 5.1% and 4.7%; and triclonal in 0% and 4.7%. The distribution of serum light-chain types between the two races was also significantly different (P=0.003, chi-square test): kappa in 53.8% and 47.6%; lambda in 43.6% and 42.8%; biclonal 2.6% and 4.7%; and triclonal in 0% and 4.7%. Conclusions Our finding that MGUS is twice as common among obese (vs. non-obese) women, and independent of race, supports the hypothesis that obesity is etiologically linked to myelomagenesis and may have public health impact. The observed 2-fold excess of MGUS among African-Americans (vs. Caucasians) of similar socio-economic status, coupled with other recent studies supports a role for susceptibility genes as the cause for racial disparity in the prevalence of MGUS. Disclosures No relevant conflicts of interest to declare.

scholarly journals Deep vein thrombosis after monoclonal gammopathy of undetermined significance and multiple myeloma

Blood ◽  
2008 ◽  
Vol 112 (9) ◽  
pp. 3582-3586 ◽  
Author(s):  
Sigurdur Y. Kristinsson ◽  
Thomas R. Fears ◽  
Gloria Gridley ◽  
Ingemar Turesson ◽  
Ulf-Henrik Mellqvist ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Gammopathy ◽  
First Year ◽  
Small Hospital ◽  
Entire Study ◽  
Crude Incidence ◽  
Vein Thrombosis ◽  
Increased Risk ◽  
Underlying Mechanisms ◽  
Undetermined Significance

Patients with multiple myeloma (MM) have an increased risk of deep venous thrombosis (DVT), particularly when treated with immunomodulatory drugs. Recently, 2 small hospital-based studies observed persons with the MM precursor condition, monoclonal gammopathy of undetermined significance (MGUS), to be at increased risk of developing DVT. Among 4 196 197 veterans hospitalized at least once at US Veterans Affairs hospitals, we identified a total of 2374 cases of MGUS, and 39 272 persons were diagnosed with DVT (crude incidence 0.9 per 1000 person-years). A total of 31 and 151 DVTs occurred among MGUS and MM patients, respectively (crude incidence 3.1 and 8.7 per 1000 person-years, respectively; P < .01). Compared with the entire study population, the relative risk (RR) of DVT after a diagnosis of MGUS and MM was 3.3 (95% confidence interval [CI], 2.3-4.7) and 9.2 (95% CI, 7.9-10.8), respectively. The most prominent excess risk of DVT was found during the first year after diagnosis of MGUS (RR = 8.4; 95% CI, 5.7-12.2) and MM (RR = 11.6; 95% CI, 9.2-14.5). Among 229 MGUS cases (9.5%) that progressed to MM, only one person had a DVT diagnosis before transformation. Our findings suggest the operation of shared underlying mechanisms causing coagulation abnormalities among patients with MGUS and MM.

Abstract 15312: Racial Disparities in Trends in Mortality From Cardiac Arrests in the United States

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Anas M Al Zubaidi ◽  
Graham Bevan ◽  
Mariam Rana ◽  
Abdul Rahman Al Armashi ◽  
Mustafa Alqaysi ◽  
...  
Keyword(s):  
United States ◽  
Cardiac Arrest ◽  
African American ◽  
African Americans ◽  
Cause Of Death ◽  
Census Data ◽  
International Classification Of Diseases ◽  
The United States ◽  
Population Based ◽  
Increased Risk

Background: African Americans are at increased risk of fatal cardiac arrests, but population-based studies exploring contemporary epidemiology are not available. We sought to identify the trend in race-specific mortality from cardiac arrest in the United States. Methods: Using the multiple cause of death database, we identified all patients (Caucasians or African Americans) who died of cardiac arrest (International Classification of Diseases, 10th revision code I46.x listed as underlying cause of death) between 1999 and 2018. Age-adjusted mortality rates were standardized to the 2000 US census data, and stratified by age group (<35 years, 35-64 years, and ≥ 65 years). Results: A total of 311,065 cardiac arrest deaths were identified, with an overall age-adjusted mortality of 53.6 per million (Caucasian: 49.1 per million, African American: 90.6 per million). Overall, age-adjusted mortality decreased from 80.1 per million persons (1999) to 44.3 per million persons (2012), followed by 8.8% increase to 48.2 (2018). Between 2012 and 2018, African Americans had higher rates of increase (10.9%) compared with Caucasians (6.9%). Largest disparities in relative changes between 2012 and 2018 occurred in patients younger than 35 years (African American: 35%, Caucasians -11%), and patients ≥ 65 years (African Americans: 8%, Caucasians 4%), figure. Conclusions: Although the mortality due to cardiac arrest has declined in the US between 1999 and 2012, a recent increase has been noted between 2012 and 2018, particularly among younger African Americans. Studies should focus on identifying causes of disparities and identifying methods to reduce the racial gap.

scholarly journals Obesity and risk of monoclonal gammopathy of undetermined significance and progression to multiple myeloma: a population-based study

2017 ◽  
Vol 1 (24) ◽  
pp. 2186-2192 ◽  
Author(s):  
Marianna Thordardottir ◽  
Ebba K. Lindqvist ◽  
Sigrun H. Lund ◽  
Rene Costello ◽  
Debra Burton ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Multiple Myeloma ◽  
Body Mass ◽  
Monoclonal Gammopathy ◽  
High Body Mass Index ◽  
Population Based ◽  
Population Based Study ◽  
Increased Risk ◽  
Key Points ◽  
Undetermined Significance

Key PointsObesity is not associated with MGUS or LC-MGUS. High body mass index during midlife is associated with increased risk of progressing from MGUS and LC-MGUS to MM and other LP diseases.

Hyperphosphorylated paratarg-7: a new molecularly defined risk factor for monoclonal gammopathy of undetermined significance of the IgM type and Waldenström macroglobulinemia

Blood ◽  
2011 ◽  
Vol 117 (10) ◽  
pp. 2918-2923 ◽  
Author(s):  
Sandra Grass ◽  
Klaus-Dieter Preuss ◽  
Alexandra Wikowicz ◽  
Evangelos Terpos ◽  
Marita Ziepert ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Gammopathy ◽  
Immunoglobulin A ◽  
Cell Receptor ◽  
Carrier State ◽  
Waldenström Macroglobulinemia ◽  
Waldenstrom Macroglobulinemia ◽  
Phosphatase Treatment ◽  
Increased Risk ◽  
Undetermined Significance

Abstract We recently described paratarg-7 (P-7), a protein of unknown function, as the target of 15% of immunoglobulin A (IgA) and IgG paraproteins in monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma. To determine the frequency of P-7 as a paraprotein target in IgM-MGUS and Waldenström macroglobulinemia (WM), sera from patients with IgM-MGUS/WM were tested for reactivity with recombinant P-7 by enzyme-linked immunoabsorbent assay. The specificity of the paraprotein-mediated reaction was shown by absorption studies and cloning of the respective B-cell receptor. The paraproteins of 18 (9 WM and 9 IgM-MGUS) of 161 patients (11%) reacted with P-7. Isoelectric focusing and phosphatase treatment showed that P-7 was hyperphosphorylated (pP-7) in all patients with an anti–P-7-specific IgM paraprotein tested. Because only 4 of 200 healthy controls (2%) were carriers of pP-7, pP-7 carrier state is associated with a significantly increased risk (odds ratio = 6.2; P = .001) for developing IgM-MGUS/MW. Family analyses showed that the pP-7 carrier state is inherited as a dominant trait. After IgA/IgG-MGUS and multiple myeloma, IgM-MGUS/WM is the second neoplasia associated with pP-7 carrier state. The dominant inheritance of pP-7 explains cases of familial IgM-MGUS/WM and enables the identification of family members at increased risk.

scholarly journals Increased risk of monoclonal gammopathy in first-degree relatives of patients with multiple myeloma or monoclonal gammopathy of undetermined significance

Blood ◽  
2009 ◽  
Vol 114 (4) ◽  
pp. 785-790 ◽  
Author(s):  
Celine M. Vachon ◽  
Robert A. Kyle ◽  
Terry M. Therneau ◽  
Barbara J. Foreman ◽  
Dirk R. Larson ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Gammopathy ◽  
Population Based ◽  
Detection Methods ◽  
Shared Environment ◽  
Serum Samples ◽  
Adjusted Risk ◽  
First Degree Relatives ◽  
Increased Risk ◽  
Undetermined Significance

Abstract We examined whether monoclonal gammopathy of undetermined significance (MGUS) is increased in first-degree relatives of multiple myeloma (MM) or MGUS patients. Probands were recruited from a population-based prevalence study (MGUS) and the Mayo Clinic (MM). Serum samples were collected from first-degree relatives older than 40 years and subjected to electrophoresis and immunofixation. The prevalence of MGUS in relatives was compared with population-based rates. Nine-hundred eleven relatives of 232 MM and 97 MGUS probands were studied. By electrophoresis, MGUS was detected in 55 (6%) relatives, and immunofixation identified 28 additional relatives for an age- and sex-adjusted prevalence of 8.1% (95% CI, 6.3 to 9.8). The prevalence of MGUS in relatives increased with age (1.9%, 6.9%, 11.6%, 14.6%, 21.0% for ages 40-49, 50-59, 60-69, 70-79, ≥ 80 years, respectively; P < .001). Using similar MGUS detection methods, there was a higher risk of MGUS in relatives (age-adjusted risk ratio [RR], 2.6; 95% CI, 1.9 to 3.4) compared with the reference population. The increased risk was seen among relatives of MM (RR, 2.0; 95% CI, 1.4 to 2.8) and MGUS probands (RR, 3.3; 95% CI, 2.1 to 4.8). The increased risk of MGUS in first-degree relatives of MGUS or MM patients implies shared environment and/or genetics.

scholarly journals Monoclonal gammopathy of undetermined significance and COVID-19: a population-based cohort study

2021 ◽  
Vol 11 (12) ◽  
Author(s):  
Saemundur Rognvaldsson ◽  
Elias Eythorsson ◽  
Sigrun Thorsteinsdottir ◽  
Brynjar Vidarsson ◽  
Pall Torfi Onundarson ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cohort Study ◽  
Odds Ratio ◽  
Monoclonal Gammopathy ◽  
Large Population ◽  
Immune Dysfunction ◽  
Population Based ◽  
Study Group ◽  
Increased Risk ◽  
Undetermined Significance

AbstractMultiple myeloma (MM) patients have increased risk of severe coronavirus disease 2019 (COVID-19) when infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Monoclonal gammopathy of undetermined significance (MGUS), the precursor of MM has been associated with immune dysfunction which may lead to severe COVID-19. No systematic data have been published on COVID-19 in individuals with MGUS. We conducted a large population-based cohort study evaluating the risk of SARS-CoV-2 infection and severe COVID-19 among individuals with MGUS. We included 75,422 Icelanders born before 1976, who had been screened for MGUS in the Iceland Screens Treats or Prevents Multiple Myeloma study (iStopMM). Data on SARS-CoV-2 testing and COVID-19 severity were acquired from the Icelandic COVID-19 Study Group. Using a test-negative study design, we included 32,047 iStopMM participants who had been tested for SARS-CoV-2, of whom 1754 had MGUS. Among these participants, 1100 participants, tested positive, 65 of whom had MGUS. Severe COVID-19 developed in 230 participants, including 16 with MGUS. MGUS was not associated with SARS-CoV-2 infection (Odds ratio (OR): 1.05; 95% confidence interval (CI): 0.81–1.36; p = 0.72) or severe COVID-19 (OR: 0.99; 95%CI: 0.52–1.91; p = 0.99). These findings indicate that MGUS does not affect the susceptibility to SARS-CoV-2 or the severity of COVID-19.

Plasma Cell Disorders

2015 ◽  
Author(s):  
Morie A. Gertz
Keyword(s):  
Multiple Myeloma ◽  
Black Women ◽  
Plasma Cell ◽  
Bone Disease ◽  
Monoclonal Gammopathy ◽  
White Women ◽  
Plasma Cells ◽  
The United States ◽  
Lytic Lesion ◽  
Undetermined Significance

Multiple myeloma represents 1.4% of all new patients with cancer and will result in an estimated 11,090 deaths in 2014. It is twice as common in black men as in white men and 2.5 times more common in black women than in white women. Myeloma is the 14th most common cause of cancer in the United States, with a median age at diagnosis of 69 years. Multiple myeloma is defined by the presence of a clonal growth of plasma cells, usually in the bone marrow, but patients may also present with extramedullary disease. Anemia and bone disease are common in patients with multiple myeloma. Multiple myeloma cells display multiple genetic abnormalities, with no one specific genetic lesion common to a majority of patients. This module describes the immunologic profile of multiple myeloma and its diagnosis, monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, plasmacytoma, plasma cell leukemia, the clinical presentation of multiple myeloma bone disease, anemia, renal impairment, hypercalcemia, and neurologic symptoms associated with multiple myeloma. Therapy for transplantation-eligible and non–transplantation-eligible patients, maintenance treatment for multiple myeloma, Waldenström macroglobulinemia, and amyloidosis are also discussed. Tables outline the risk of monoclonal gammopathy of undetermined significance evolution, the myeloma staging system, recommended diagnostic testing and uniform response criteria for myeloma, and commonly used regimens in the treatment of myeloma. Figures include a magnetic resonance image showing multiple plasmacytomas, tibial lytic lesion from myeloma, calvarial lytic lesions, a positron emission tomographic scan in a myeloma patient, and hyperviscosity causing retinal hemorrhages. This review contains 5 highly rendered figures, 5 tables, and 149 references.

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