A Nested Case-Control Study of Monoclonal Gammopathy of Undetermined Significance in the Multiethnic Cohort Study.

Monoclonal gammopathy of undetermined significance (MGUS) is a necessary precursor of multiple myeloma (MM). Compared to non-Hispanic Whites (Whites), African Americans experience about 2-fold greater, and Asian Americans 50% lower, occurrence of MGUS and MM. We examined determinants of MGUS and progression to MM or other plasma cell neoplasms (PCN) among Japanese American, African American, Latino, Native Hawaiian, and White participants in a case-control study nested in the Multiethnic Cohort (MEC) Study. Presumptive cases included MEC participants 65+ years old initially screened using the Medicare billing code for paraproteinemia along with those with MM/PCN at least one year after blood draw. Presumptive controls had no Medicare billing code or MM. Laboratory confirmation resulted in 426 confirmed MGUS cases (370 non-IgM and 56 IgM) and 863 MGUS-free controls. We used multivariable logistic regression and Cox regression to estimate associations with MGUS and MGUS progression. The distribution of immunoglobulin (Ig) isotypes differed by race/ethnicity (P=0.005): Japanese Americans had the lowest (11.0%) and Native Hawaiians the highest (23.5%) proportion of IgA. Each unit increase in BMI (kg/m2) was associated with a 6% increase in non-IgM MGUS (95% CI= 3-9%) among all racial/ethnic groups combined. BMI was also significantly associated within most racial/ethnic groups, especially among Native Hawaiians (13% increase per BMI unit), and with IgA and IgG MGUS. Progression to MM or other PCN was associated with an M-spike >1.5 g/dL, but not with BMI. BMI was the main determinant associated with MGUS, but not with progression. Isotype distribution differed between racial/ethnic groups.