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Multiple Myeloma Subtypes Linked to Patients' African Ancestry

NEW YORK (GenomeWeb) – A team led by researchers at the Mayo Clinic has delved into the genetic contributors to multiple myeloma risk in individuals with varying levels of African and European ancestry.

"Our findings provide important information that will help us determine the mechanism by which myeloma is more common in African Americans, as well as help us in our quest to find out what causes myeloma in the first place," corresponding author Vincent Rajkumar, a hematology researcher at the Mayo Clinic, said in a statement.

For a study published in the Blood Cancer Journal yesterday, Rajkumar and colleagues from the Mayo Clinic, the University of Sheffield, and genetic testing lab DNA Diagnostics Center performed cytogenetic analyses, genotyping, and genetic ancestry profiling on samples from 881 individuals with monoclonal gammopathy — a set of blood plasma cell neoplasms ranging from non-cancerous conditions that increase myeloma risk, such as monoclonal gammopathy of undetermined significance (MGUS), to multiple myeloma itself.

"Previous efforts to understand this disparity have relied on self-reported race rather than on genetic ancestry, which may have resulted in bias," Rajkumar explained. "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."

Prior studies described a general rise in multiple myeloma or MGUS risk, combined with earlier disease onset, in African American and West African individuals, the researchers noted. But the new work provides a clearer look at ties between genetic ancestry and the prevalence of specific disease subtypes.

Based on fluorescence in situ hybridization analyses of plasma cell chromosomes — along with tumor cytogenetic analyses, array-based genotyping, and ancestry estimates using the Geographic Population Structure Origins tool — the team found that three cytogenetic subtypes were significantly overrepresented in the 120 participants with 80 percent or greater ancestry from Africa.

The researchers estimated that the risk of developing one of three multiple myeloma subtypes — marked by the so-called t(11;14), t(14;16), and t(14;20) translocations, affecting an immunoglobulin heavy chain gene on chromosome 14 — jumped by roughly 6 percent for each 10 percent increase in African ancestry.

Compared to 235 individuals with less than 0.1 percent African ancestry according to their genomes, the individuals with at least 80 percent African ancestry also appeared less likely to develop multiple myelomas marked by trisomies and specific chromosome 13 alterations.

"Future studies will include enlarging our [80 percent or greater African ancestry] cohort and increasing the granularity of our studies with regards to specific regions within Africa," the authors concluded. "Understanding the cause of health disparities in monocloncal gammopathies has the potential to provide previously unrecognized interventions."

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