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.

Characteristics of long‐term survivors with multiple myeloma: A National Cancer Data Base analysis

“…11 In addition, estrogen could decrease myeloma tumor growth by inhibiting interleukin 6 via the PIAS3-STAT3 pathway. 3,14,15 The difference in results could be explained by health care disparities and socioeconomic differences between races. However, some previous studies have demonstrated that African American individuals had a 1.3-fold to 2-fold higher mortality risk compared with white individuals.…”

“…However, some previous studies have demonstrated that African American individuals had a 1.3-fold to 2-fold higher mortality risk compared with white individuals. 3,14,15 The difference in results could be explained by health care disparities and socioeconomic differences between races. [16][17][18] After statistical adjustment of other sociodemographic factors in the current study, race was no longer found to be a significant prognostic factor, a finding that is consistent with the results of a previous population-based study.…”

The CCND1 c.870G risk allele is enriched in individuals of African ancestry with plasma cell dyscrasias

“…Many previous studies evaluating the mechanism of racial disparities in MGUS/MM have assessed race using self-reported demographic data rather than utilizing ancestry informative single-nucleotide polymorphisms (SNPs) as a method to determine the proportion of racial admixture. Using SNP data, we have recently identified a higher prevalence of IgH translocations t (11;14), t(14;16) and t(14;20) in individuals with ≥80% African ancestry 11 . Enrichment of t (11;14) was confirmed in a more recent study 12 .…”

“…Enrichment of t (11;14) was confirmed in a more recent study 12 . As an extension to our previous work 11 , we investigated which, if any, of the germline risk alleles previously associated with MM or MGUS risk, survival or risk of development of t(11;14) 13 (Supplemental Table 1) are enriched in individuals of African ancestry in our cohort of patients with plasma cell dyscrasias.…”

Population Genetic Considerations for Using Biobanks as International Resources in the Pandemic Era and Beyond

“…This criterion is believed to account for the participants genetic background and supposedly allow controlling for population genetic structure (e.g. Baughn et al, 2018Baughn et al, , 2020. A numerical example of how a false positive association can be created due to population stratification is shown in Table 1 (Hellwege et al, 2017).…”