Differences in genomic abnormalities among African individuals with monoclonal gammopathies using calculated ancestry

Abstract

Multiple myeloma (MM) is two- to three-fold more common in African Americans (AAs) compared to European Americans (EAs). This striking disparity, one of the highest of any cancer, may be due to underlying genetic predisposition between these groups. There are multiple unique cytogenetic subtypes of MM, and it is likely that the disparity is associated with only certain subtypes. Previous efforts to understand this disparity have relied on self-reported race rather than genetic ancestry, which may result in bias. To mitigate these difficulties, we studied 881 patients with monoclonal gammopathies who had undergone uniform testing to identify primary cytogenetic abnormalities. DNA from bone marrow samples was genotyped on the Precision Medicine Research Array and biogeographical ancestry was quantitatively assessed using the Geographic Population Structure Origins tool. The probability of having one of three specific subtypes, namely t(11;14), t(14;16), or t(14;20) was significantly higher in the 120 individuals with highest African ancestry (≥80%) compared with the 235 individuals with lowest African ancestry (<0.1%) (51% vs. 33%, respectively, p value = 0.008). Using quantitatively measured African ancestry, we demonstrate a major proportion of the racial disparity in MM is driven by disparity in the occurrence of the t(11;14), t(14;16), and t(14;20) types of MM.

Fig. 1. Percent African ancestry by self-reported race in cohort of 881 individuals.

Distribution of the percent of African ancestry based on the sum of all 10 African regional ancestries within the 881 samples in this study by self-report race in 393 samples or non-reported race information in 488 samples

Fig. 2. Probability of either t(11;14),t(14;16) or t(14;20) or any trisomy in relation to percent African ancestry.

Smoothing spline was used to visualize the relationship between percentage of African genetics and probability of of t(11;14), t(14;16) or t(14;20) or of any trisomy