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

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.