The mechanism driving the increased prevalence of t(11;14), t(14;16), and t(14;20) translocations among individuals of African descent is unclear. It is possible that this group faced evolutionary pressure to mount elevated immune responses to antigens, which could have given rise to cellular processes resulting in higher risk of chromosome 14 translocations, Dr Rajkumar speculated.

Researchers involved in the study are currently looking at germline SNPs for the 881 patients to determine whether specific risk alleles may help explain the increased incidence of myeloma in the African ancestry cohort as well as their better survival outcomes, said Linda B. Baughn, PhD, FACMG, codirector of the Genomics Laboratory at the Mayo Clinic and lead author of the study.


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Prior research has suggested that, “while environmental factors contribute to the risk of multiple myeloma, the racial disparity is most likely genetic,” Dr Rajkumar said. A study comparing Ghanaian men with white men from Minnesota reported that MGUS was twice as prevalent in the former group regardless of age and education status.2 Furthermore, Dr Rajkumar and his colleagues have found that MGUS prevalence is higher among black women in the southern United States compared with white women of similar socioeconomic status, further bolstering the idea that the disparity is likely driven by genetic factors.

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The current study found that, along with higher frequency of t(11;14), t(14;16), and t(14;20) among individuals of African descent, individuals in the African ancestry cohort were less likely to be in the older age group (aged 70-79 years) and more likely to be female. The reasons for these differences are unclear, Dr Rajkumar said.

These findings underscore the importance of pathology labs probing specifically for the t(11;14) subtype in patients, especially in African Americans, which many labs already do because t(11;14) is a common subtype, Dr Baughn said. Future research should will center around conducting more comprehensive genomic analyses to understand if the nature of the t(11;14) translocation is similar between people of African and European descent, she added.

Understanding the specific subtypes of myeloma that are more prevalent among Africans and African Americans could translate into better disease management. A drug called venetoclax targets the t(11;14) translocation and is approved for patients with chronic lymphocytic leukemia (CLL). “There are data that myeloma patients with t(11;14) respond to venetoclax, and we need more studies to determine if the effect is similar in African Americans.” Dr Baughn said.

References

  1. Baughn 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(10):96.
  2. Landgren O, Katzmann JA, Hsing AW, et al. Prevalence of monoclonal gammopathy of undetermined significance among men in Ghana. Mayo Clin Proc. 2007;82(12):1468-1473.