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Three gene types drive MM disparity in African Americans


 

Photo by Rhoda Baer

Cancer patient receiving treatment

Researchers say they may have determined why African Americans have a two- to three-fold increased risk of multiple myeloma (MM) compared to European Americans.

The team genotyped 881 MM samples from various racial groups and identified three gene subtypes—t(11;14), t(14;16), and t(14;20)—that explain the racial disparity.

They found that patients with African ancestry of 80% or more had a significantly higher occurrence of these subtypes compared to individuals with African ancestry less than 0.1%.

And these subtypes are driving the disparity in MM diagnoses between the populations.

The researchers state that previous attempts to explain the disparity relied on self-reported race rather than quantitatively measured genetic ancestry, which could result in bias.

“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,” said study author Vincent Rajkumar, MD, of the Mayo Clinic in Rochester, Minnesota.

He and his colleagues reported their findings in Blood Cancer Journal.

All 881 samples had abnormal plasma cell FISH, 851 had a normal chromosome study, and 30 had an abnormal study.

Median age for the entire group was 64 (range, 26–90), with 35.4% in the 60–69 age category. More samples were from men (n=478, 54.3%) than women (n=403, 45.7%).

Researchers observed no significant difference between men and women in the proportion of primary cytogenetic abnormalities.

Of the 881 samples, the median African ancestry was 2.3%, the median European ancestry was 64.7%, and Northern European ancestry was 26.6%.

Thirty percent of the entire cohort had less than 0.1% African ancestry, and 13.6% had 80% or greater African ancestry.

Using a logistic regression model, the researchers determined that a 10% increase in the percentage of African ancestry was associated with a 6% increase in the odds of detecting t(11;14), t(14;16), or t(14;20) (odds ratio=1.06, 95% CI: 1.02–1.11; P=0.05).

The researchers plotted the probability of observing these cytogenetic abnormalities with the percentage of African ancestry and found the differences were most striking in the extreme populations—individuals with ≥80.0% African ancestry and individuals with <0.1% African ancestry.

Upon further analysis, the team found a significantly higher prevalence of t(11;14), t(14;16), and t(14;20) in the group of patients with the greatest proportion of African ancestry (P=0.008) compared to the European cohort.

The researchers said the differences only emerged in the highest (n=120 individuals) and lowest (n=235 individuals) cohorts. Most patients (n=526, 60%) were not included in these extreme populations because they had mixed ancestry.

The team observed no significant differences when the cutoff of African ancestry was greater than 50%.

“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,” Dr. Rajkumar said.

The research was supported by the National Cancer Institute of the National Institutes of Health and the Mayo Clinic Department of Laboratory Medicine and Pathology and Center for Individualized Medicine. One study author reported relationships with Celgene, Takeda, Prothena, Janssen, Pfizer, Alnylam, and GSK. Two authors reported relationships with the DNA Diagnostics Center.

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