Biological determinants of health disparities in multiple myeloma.

Multiple myeloma is a rare plasma cell cancer, and incidence rates among patients of African descent are about twice those among patients of European descent. Rates of multiple myeloma vary among different populations, but the reasons for the racial disparities in multiple myeloma are largely unknown. Epidemiology has identified risk factors for multiple myeloma including race, advanced age, gender, family history, and exposure to different genetic toxins including radiation. Race and ancestry play a large role in predicting the risk for multiple myeloma, yet there exists a paucity of literature that explores the molecular contribution of race and ancestry to disease. In this review, we describe the relevant literature that describes the observed racial differences according to distinct tumor immunobiological and ancestral differences in populations.

Over one-third of African-American MGUS and multiple myeloma patients are carriers of hyperphosphorylated paratarg-7, an autosomal dominantly inherited risk factor for MGUS/MM.

As hyperphosphorylated paratarg-7 (pP-7) carrier state was shown to be the first molecularly defined autosomal dominantly inherited risk factor for monoclonal gammopathy of unknown significance (MGUS) and multiple myeloma (MM) in a European population, the prevalence of pP-7 carrier state among African-Americans who have a significantly higher incidence of MGUS/MM is of interest. We therefore determined pP-7 carrier state and paraproteins with specificity for P-7 in African-American, European and Japanese patients with MGUS/MM and healthy controls. By isoelectric focusing and ELISA, a paratarg-7-specific paraprotein and the associated pP-7 carrier state was observed in 30/81 (37.0%) African-American, 42/252 (16.7%) European and 7/176 (4.0%) Japanese MGUS/MM patients (p < 0.001). A pP-7 carrier state was found in 11/100 (11.0%) African-American, 8/550 (1.5%) European and 1/278 (0.4%) Japanese healthy controls (p < 0.001), resulting in an odds ratio for MGUS/MM of 4.8 (p < 0.001) among African-American, 13.6 among European (p < 0.001) and 11.5 (p = 0.023) among Japanese carriers of pP-7. We conclude that pP-7 carriers are most prevalent among African-Americans, but a pP-7 carrier state is the strongest molecularly defined single risk factor for MGUS/MM known to date in all three ethnic groups. The high prevalence of pP-7 carriers among African-American patients emphasizes a predominant role of this genetic factor in the pathogenesis of these diseases. The large number of pP7 African-American patients and controls should facilitate the identification of the SNP or mutation underlying the pP-7 carrier state.

Prevalence of monoclonal gammopathy of undetermined significance in Thailand.

Individuals with monoclonal gammopathy of undetermined significance (MGUS) develop multiple myeloma and related malignancies at the rate of 1% per year. Given differences in ethnicity, data on prevalence and risk factors of MGUS in Thai population will be helpful in understanding the pathogenesis of plasma cell disorders and designing an early cancer detection strategy. Subjects of 50 years or older were included. Demographic data and suspected risk factors were collected. Monoclonal proteins were detected using serum protein electrophoresis. Serum was obtained from 3,260 participants; 1,104 males (33.9%) and 2,156 females (66.1%). The median age was 57 years (range 50-93 years). Monoclonal proteins were detectable in 2.3% (95% confidence interval [CI] 1.8-2.8). M spikes were found in gamma- and beta-globulin regions in 50 (1.5%) and 25 (0.8%) subjects, respectively. The prevalence of MGUS in subjects 50-59, 60-69, and 70 years or older was 2.0% (41/1,975), 2.6% (22/851), and 2.8% (12/434), respectively. By multivariate analysis, MGUS was associated with living outside Bangkok (odds ratio 2.25, 95% CI 1.11-4.58). The overall prevalence of MGUS in the Thai population was 2.3%, which was lower than that in Western countries, but comparable to that in Japan.

Disparities in the prevalence, pathogenesis and progression of monoclonal gammopathy of undetermined significance and multiple myeloma between blacks and whites.

There is marked racial disparity in the incidence of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma, with a two to threefold increased risk in blacks compared with whites. The increased risk has been seen both in Africans and African Americans. Similarly, an increased risk of monoclonal gammopathies in blacks compared with whites has been noted after adjusting for socioeconomic and other risk factors, suggesting a genetic predisposition. The higher risk of multiple myeloma in blacks is likely a result of the higher prevalence of the premalignant MGUS stage; there are no data to suggest that blacks have a higher progression rate of MGUS to myeloma. Studies are emerging that suggest the baseline cytogenetic characteristics, and progression may differ by race. In contrast, to the increased risk noted in blacks, studies suggest that the risk may be lower in certain racial and ethnic groups, notably persons from Japan and Mexico. We review the literature on racial disparity in the prevalence, pathogenesis and progression of MGUS and multiple myeloma between blacks and whites. We also discuss future directions for research that could inform management of these conditions and positively influence patient outcomes.

Prevalence of monoclonal gammopathy of undetermined significance in an elderly urban Korean population.

Research on the epidemiology of monoclonal gammopathy of undetermined significance (MGUS) is limited in Korea. The aim of this study was to determine the prevalence and characteristics of MGUS in an elderly urban Korean population. A random sample of 1118 Korean elders was selected from residents aged 65 years or older living in Seongnam, Korea 1 year from August 2005. We obtained plasma samples remaining after scheduled tests for the Korean Longitudinal Study on Health and Aging. The mean age of the study population was 72 years (range, 65-97 years). To screen for MGUS, immunofixation and free light-chain (FLC) assays were performed. Age-adjusted and gender-adjusted MGUS prevalence rates in 680 responders were estimated as 3.3% [95% confidence interval (CI) = 2.0-4.6%], and the estimated age-adjusted prevalence of MGUS was 4.3% in men (95% CI = 1.9-6.6%) and 2.6% in women (95% CI = 1.0-4.2%). Abnormal FLC ratios were detected in 10% of MGUS cases. Multivariate analysis of 945 participants revealed that significant risk factors for MGUS included advanced age, male sex, hyperproteinemia, increased erythrocyte sedimentation rate, and abnormal FLC ratio. MGUS is less prevalent among elderly Koreans (3.3%) than other races. This is the first study to estimate the prevalence of MGUS in the Korean elderly population. Our findings should be confirmed with additional studies analyzing follow-up samples from 2010.

Patterns of monoclonal immunoglobulins and serum free light chains are significantly different in black compared to white monoclonal gammopathy of undetermined significance (MGUS) patients.

Monoclonal gammopathy of undetermined significance (MGUS), the precursor to multiple myeloma, is more common in blacks than whites. The serum free light chain (sFLC) assay is an important prognostic test in MGUS, but no study has evaluated sFLC levels and ratios in black MGUS patients. One-hundred and twenty-five black MGUS patients at two urban centers were compared to the white population of the Mayo Clinic. The median age for blacks was 73 years [41-94] and 75% were male. The M-protein isotype in blacks was 81% IgG, 13% IgA, 2% IgM, and 4% biclonal compared to 70%, 12%, 16%, and 2%, respectively, in whites, (P < 0.0005). The median M-protein concentration for blacks was 0.44 gm/dL (trace-2.33) compared to 1.2 gm/dl in whites. An abnormal sFLC ratio was present in 45% of black compared to 33% of white (P = 0.01) patients. Using the Mayo Clinic risk model, black patients had a significantly lower proportion of higher risk MGUS compared to whites: low 43%, low-intermediate 45%, high-intermediate 10%, and high 2% (P = 0.014). Black patients with MGUS have significantly different laboratory findings compared to whites. The biologic basis for these disparities and their effect on prognostic assessment is unknown. Prognostic models based on these biomarkers should be used cautiously in nonwhite populations.

Increased incidence of monoclonal gammopathy of undetermined significance in blacks and its age-related differences with whites on the basis of a study of 397 men and one woman in a hospital setting.

Serum samples from 398 individuals (270 whites and 128 blacks) exhibiting quantitatively normal amounts of five typically seen fractions (albumin, alpha 1-globulin, alpha 2-globulin, beta-globulin, and gamma-globulin) in serum protein electrophoresis and showing no evidence of multiple myeloma, other immunoproliferative diseases, or any of the other diseases known to produce monoclonal proteins were tested for monoclonal gammopathy of undetermined significance (MGUS) by immunofixation electrophoresis. No individual in the study had a serum protein electrophoresis pattern suggestive of monoclonal protein gammopathy. Except for one 37-year-old woman, all subjects were men. Subjects were divided into seven age groups: 20 to 29 years (I), 30 to 39 years (II), 40 to 49 years (III), 50 to 59 years (IV), 60 to 69 years (V), 70 to 79 years (VI), and all over 79 years (VII) of age. Considering all subjects in a given race, blacks had two times (14.8%) higher incidence of MGUS than whites (7.8%); this difference was statistically significant. An increased incidence of MGUS in blacks when compared with whites prevailed in each age group, and the difference was statistically significant in all age groups except group II. No MGUS was found in groups I and III in either race. Both races showed a threefold increase in incidence of MGUS from group II to group VII. No routine laboratory test such as erythrocyte sedimentation rate in subjects with MGUS was significantly different than that in age- and race-matched individuals without MGUS. These results show that the incidence of MGUS is higher in the group (blacks) also known to have a higher prevalence of multiple myeloma.