Researchers Identify 3 Genetic Alterations Associated with Higher Risk of Myeloma in African-Americans

Researchers have identified three genetic alterations associated with the known twofold to threefold risk of multiple myeloma among African-Americans.

The study, “Differences in genomic abnormalities among African individuals with monoclonal gammopathies using calculated ancestry,” was published in the Blood Cancer Journal.

Multiple myeloma is the most common form of blood cancer affecting African-Americans, who can experience onset some four years earlier compared with European-Americans. But when African-American patients have access to proper care, they often have a better treatment response and overall survival than European-Americans.

These data suggest that African-Americans may have a genetic predisposition to specific types of multiple myeloma that are less aggressive or respond better to treatment.

Many multiple myeloma patients have a type of genetic alteration called translocations — where chromosome segments and their genes change positions within the same chromosome or into another chromosome.

Translocations most associated with standard risk of developing multiple myeloma are t(11;14) or t(6;14), while t(4;14), t(14;16) and t(14;20) have been associated with a high risk. The designation t(11;14) means there is a translocation between chromosome 11 and chromosome 14.

Researchers at the Mayo Clinic have identified the genetic alterations and ancestry of 881 patients (478 men and 403 women) of various racial groups and evaluated potential associations between genetic alterations and high African ancestry. Patients’ samples were obtained from the Mayo Clinic Genomics Laboratory.

“Previous efforts to understand this disparity have relied on self-reported race rather than on genetic ancestry, which may have resulted in bias,” Vincent Rajkumar, MD, the study’s senior author and a hematologist at Mayo Clinic, said in a 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.”

Patients’ mean age was 64 at the time of genetic analysis — with 35.4% of patients in the 60-69 age category — and self-reported race was available for 393 patients.

The median African ancestry of 161 self-reporting patients was 80%, and the majority (96.9%) of these patients had at least 50% African ancestry.

The 120 individuals with the highest African ancestry (greater than 80%) displayed a significantly higher frequency of t(11;14), t(14;16), or t(14;20), compared with the 235 individuals with the lowest African ancestry (less than 0.1%).

Thus, the data revealed that high African ancestry is associated with a higher frequency of one standard-risk translocation and two high-risk translocations.

“Using quantitatively measured African ancestry, we demonstrate a major proportion of the racial disparity in [multiple myeloma] is driven by disparity in the occurrence of the t(11;14), t(14;16), and t(14;20) types of MM,” the researchers stated.

The team noted that whether there is a common mechanism resulting specifically in the generation of these three translocations remains unclear and that additional studies are required to understand the underlying mechanisms of these differences in predisposition between Africans and Europeans.

They believe that future use of ancestry markers for the precise characterization of a patient’s genetic history will help clarify how race contributes to health differences, to better understand what causes myeloma, and to provide new therapeutic approaches.

The team plans to conduct this type of analysis in a larger group of patients with the highest African ancestry, including specific regions within Africa.

Rajkumar also noted that because treatment response in myeloma patients is associated with specific genetic subtypes of the cancer, these findings will help the development of more effective treatment strategies for African-Americans myeloma patients.