Three Genetic Types Drive Higher Prevalence of MM in African Americans

Multiple myeloma (MM) occurs 2 to 3 times more frequently in Americans of African descent than in Americans of European descent, and a new study¹ has identified 3 gene types that account for this disparity.

The paper, published in Blood Cancer Journal, demonstrated that the disparity is largely driven by disparities in the occurrence of the t(11;14), t(14;16), and t(14;20) subtypes of MM.

“We sought to identify the mechanisms of this health disparity to help us better understand why myeloma occurs in the first place and provide insight into the best forms of therapy,” Vincent Rajkumar, MD, a hematologist at Mayo Clinic and senior author of the study, said in a statement.

The researchers studied 881 patients with monoclonal gammopathies. While previous research into disparities in prevalence of disease have relied on self-reported race, this study identified the ancestry of patients through DNA sequencing. Self-reported race can result in bias, but the DNA sequencing allowed researchers to determine ancestry more accurately, Rajkumar said.

In the entire cohort, the media African ancestry was 2.3%, the median European ancestry was 64.7%, and the median Northern European ancestry was 26.6%. To better observe differences in the prevalence of MM subtypes, the authors separated the cohort into the most extreme populations with regard to African ancestry.

“Although many individuals in the US are of mixed ancestry, ancestral characterization of patient cohorts is required to fully understand how the role of human genetic variation associated with ancestry impacts health disparities,” the authors wrote.

They found that the probability of having 1 of the 3 subtypes associated with higher risk of MM was significantly higher in the 120 individuals who had at least 80% African ancestry compared with the 235 individuals who had less than 0.1% African ancestry.

Previous research² has shown that despite being more likely to be diagnosed with MM, African Americans are underrepresented in MM disease research. As a result, improved overall survival for MM has largely been observed in Caucasian patients.

“There are efforts to enroll more minorities in clinical studies, and this is important,” Rajkumar said. “However, it is equally, if not more important, to determine the mechanisms of racial disparities in terms of why cancers occur more often in certain racial groups. Our findings provide important information that will help us determine the mechanism by which myeloma is more common in African Americans, as well as help us in our quest to find out what causes myeloma in the first place.”

Reference

1. Baugh LB, Pearce K, Larson D, et al. Differences in genomic abnormalities among African individuals with monoclonal gammopathies using calculated ancestry. Blood Cancer J. 2018;8:96. doi: 10.1038/s41408-018-0132-1.

2. Manoklovic A, Christofferson A, Liang WS, et al. Comprehensive molecular profiling of 718 multiple myelomas reveals significant differences in mutation frequencies between African and European descent cases. 2017;13(11):e1007087. doi: 10.1371/journal.pgen.1007087.