Image by Spencer Phillips
DNA helix
Researchers say they have identified significant genetic differences between African-American patients with multiple myeloma (MM) and Caucasian patients with the disease.
For example, the researchers found that African Americans were more likely to have mutations in BCL7A, BRWD3, and AUTS2, but Caucasians were more likely to have mutations in IRF4 and TP53.
“A cancer therapy that targets TP53 would not be as effective for African Americans with multiple myeloma as it would be for a white population because doctors would be trying to fix the wrong mutated gene,” said Zarko Manojlovic, PhD, of the University of Southern California in Los Angeles.
Dr Manojlovic and his colleagues conducted this research and detailed the results in PLOS Genetics.
The researchers analyzed genetic sequencing data and clinical data from 718 MM patients participating in the MMRF CoMMpass Study.
Race was reported by the patients, but the researchers also used the genetic data to determine that 127 patients were of African descent and 591 were of European descent. The researchers noted that the mean European admixture among self-reported African Americans was 31% (range; 11%-67.8%). And the mean west-African admixture among self-reported Caucasians was 0.1% (range; 0-34.3).
The African-American patients were significantly more likely than the Caucasians to have early onset MM (at ages 40-49)—11% and 4.6%, respectively (P=0.004). And Caucasians were significantly more likely than African Americans to have late-onset MM (at ages 70-79)—22% and 14%, respectively (P=0.04).
There was no significant difference in overall survival based on race, age of onset, or MM karyotype in this population.
Mutations in the following genes occurred at significantly higher frequencies in African-American patients than in Caucasians: RYR1, RPL10, PTCHD3, BCL7A, SPEF2, MYH13, ABI3BP, BRWD3, GRM7, AUTS2, PARP4, PLD1, ANKRD26, DDX17, and STXBP4.
On the other hand, Caucasians had a significantly higher frequency of mutations in IRF4 and TP53. In fact, there was a TP53 somatic mutation frequency of 6.3% in Caucasians and 1.6% in African Americans (P=0.035).
“One of the most surprising discoveries from this large cohort is that cancers from patients of European descent were 6 times more likely than their African-descent counterparts to have mutations in TP53, a known tumor suppressor gene,” Dr Manojlovic said.
“Biologically speaking, higher mutation rates in this gene should lead to overall lower survival rates among patients of European descent, but that does not correlate with what we see in clinical outcomes. Going forward, we hope to functionally validate these results for more insight into the underlying biology.”
“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,” added study author John D. Carpten, PhD, of the University of Southern California.
“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. There are clearly molecular differences between African-American and Caucasian multiple myeloma cases, and it will be critical to pursue these observations to better improve clinical management of the disease for all patients.”
