African Americans Are More Likely to Have MM, but Are Underrepresented in Research

While African Americans are 3 times more likely than Caucasians to be diagnosed with multiple myeloma (MM)—and are twice as likely to die of the disease—they are underrepresented in MM disease research. Advances in the treatment of MM may have left this patient population behind—improved overall survival for MM has predominantly been observed in patients of Caucasian descent. A newly published study that represents comprehensive genomic analysis of tumor type in patients of African descent seeks to bring much-needed clarity to potential ancestry-related differences in the biological mechanisms of MM.

The study, led by Zarko Manojlovic, PhD, of the University of California’s Keck School of Medicine and published in PLOS Genetics, prospectively observed the natural history of MM through a comprehensive profiling of 1000 MM cases at diagnosis, with multiple biological and clinical follow-up points. Patients reported their ethnicity, which allowed researchers to perform genomic analyses to assess differences among tumors based on self-reported race as well as on genetic ancestry data. A total of 127 African-American patients and 591 Caucasian patients were included in all downstream analyses.

The researchers observed a 2-fold increase in early-age onset of MM (disease onset from 40 to 49 years of age) among African-American patients (11%) versus Caucasian patients (4.6%). They also identified a reverse effect in later ages of onset (between 70 and 79 years of age), with a significantly higher frequency in Caucasian patients (22%) than in African-American patients (14%).

The following differences in genetic mutations between the 2 populations were also observed:

• There were significantly higher frequencies of IRF4 and TP53 mutations in Caucasian patients than in African-American patients. Further investigation demonstrated that TP53 mutations were strongly associated with cases of MM in patients with high European ancestry, suggesting that a therapy targeting this mutation might be less effective for African-American patients than it would be for Caucasian patients.
• FAM46C mutations were present in 8.3% of the Caucasian patients and in 12.6% in African American patients.
• Three genes with significantly higher mutation frequency in African-American patients are also involved in other B-cell malignancies: BCL7A is involved in non-Hodgkin lymphoma, the protein encoded by BRWD3 is believed to have a chromatin-modifying function, and AUTS2 is involved in acute lymphoblastic leukemia and other cancers.

It is critical to better understand the difference between MM tumors in these 2 patient populations, the authors conclude, in order to improve clinical management of the disease for all patients, not just for a subset of those diagnosed with the disease. “We in the cancer genomics community have a responsibility to ensure that our studies represent true population diversity so we can understand the role of ancestry and biology in health outcomes,” fellow study author John D. Carpten, PhD, told USC News. “The new candidate myeloma genes we identified in the African-American population may have been overlooked because of the lack of diversity in previous genomic efforts.”