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African Ancestry and Genetic Alterations Leading to Multiple Myeloma

By: Joseph Fanelli
Posted: Friday, February 1, 2019

Three genetic alterations—t(11;14), t(14;16), or t(14;20)—may be associated with a higher risk of multiple myeloma among African American individuals, according to findings reported in Blood Cancer Journal. S. Vincent Rajkumar, MD, of the Mayo Clinic, Rochester, Minnesota, and colleagues focused on the mechanisms of this racial disparity, in the hope that their findings may lead to the development of more effective treatment strategies for African American patients with myeloma.

“Previous efforts to understand this disparity have relied on self-reported race rather than on genetic ancestry, which may have resulted in bias,” explained Dr. Rajkumar in a Mayo Clinic press release. “A major new aspect of this study is that we identified the ancestry of each patient through DNA sequencing, which allowed us to determine ancestry more accurately.”

The investigators focused on 881 patients (478 men and 403 women) with monoclonal gammopathies who had undergone uniform testing to identify primary cytogenetic abnormalities. DNA from bone marrow samples underwent genotyping, and biogeographic ancestry was quantitatively assessed. Most of the patients (96.9%) had at least 50% African ancestry.

For the 120 individuals with the highest African ancestry (at least 80%), the probability of having 1 of the 3 genetic alterations was significantly higher than in the 235 individuals with the lowest African ancestry (up to 0.1%): 51% vs. 33%, respectively. The individuals with high African ancestry also displayed a lower prevalence of 13q deletion/monosomy 13 as well as a trend toward a lower prevalence of trisomy (with or without immunoglobulin heavy chain translocation) compared with individuals with the least African ancestry.

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

Disclosure: The study authors’ disclosure information may be found at nature.com.



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