27 November 2017

Experts have called for more research to help identify effective blood cancer treatments for people of African descent.

The plea comes after the largest and most ethnically diverse genomics study of multiple myeloma showed that although African-American men are three times more likely to be diagnosed with multiple myeloma, most scientific research on the disease has been based on Caucasian populations.

Research led by a team at the Keck School of Medicine at the University of Southern California (USC) says African-Americans are the most at-risk population for multiple myeloma and are twice as likely than those of European descent to die from the disease.

Because of genetic differences between the populations, disease progression is different, which means specific targeted therapies are needed, emphasised Zarko Manojlovic, lead author of the study.

The study, published in PLOS Genetics, says multiple myeloma patients of European descent are six times more likely than their African peers to have mutations in the TP53 gene, while African-Americans are more likely to have mutations in BCL7A.

"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 Manojlovic, assistant professor of research translational genomics at the Keck School of Medicine.

The study team analysed the genetic sequencing data of 718 multiple myeloma patients and found that African-Americans had increased mutations in the genes BCL7A, BRWD3 and AUTS2, while white people had more mutations in the genes TP53 and IRF4.

"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," said senior author John D. Carpten, who is chair of the Department of Translational Genomics at the Keck School of Medicine.

He said that genomics experts must ensure their studies represent true population diversity to enable an understanding of the role of ancestry and biology in health outcomes.

“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,” he added.

Source: Manojlovic Z et al. (2017) Comprehensive molecular profiling of 718 Multiple Myelomas reveals significant differences in mutation frequencies between African and European descent cases. PLoS Genet13(11): e1007087. https://doi.org/10.1371/journal.pgen.1007087

Link: http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1007087


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