New research from investigators at the Keck School of Medicine of USC has identified a key genetic variant that contributes to the increased risk of developing acute lymphoblastic leukemia (ALL) among children of Hispanic/Latino origin. The variant, located on the IKZF1 gene, was found using genetic fine-mapping analysis, a statistical method that allows researchers to better understand the individual effects in genetic variants in a genomic region.
Details of the team’s research are published in the journal Cell Genomics.
“Combined with the fact that around 30% of Hispanic/Latino people in the United States carry this gene variant, but it’s basically absent in people of predominantly European ancestry, we think it’s an important contributor to the increased ALL risk among this group,” says lead author, Adam de Smith, PhD, an assistant professor of population and public health sciences and a member of the USC Norris Comprehensive Cancer Center at the Keck School of Medicine.
In addition to the discovery of the IKZF1 gene variant, the Keck team also conducted research aimed at better understanding how it affects the development of ALL via its influence on B-cell development, a type of white blood cell that is disrupted in ALL.
“Together, the analyses in our study provide the statistical, biological and evolutionary insights behind this increased risk, and may ultimately aid scientists working to develop screening tools and therapies for ALL,” notes Charleston Chiang, PhD, an associate professor of population and public health sciences and associate director of the Center of Genetic Epidemiology at Keck and the study’s co-senior author.
For their work, the researchers tapped the California Cancer Records Linkage Project to analyze genetic data aimed at discovering why Hispanic/Lation children have an elevated risk of ALL. Their data included:
- 1,878 Hispanic/Latino children in California with ALL and 8,411 without the condition;
- 1,162 non-Hispanic white children with ALL and 57,341 without; and
- 318 East Asian children with ALL and 5,017 without.
The investigators homed in on IKZF since it was known to be associated with ALL but had not previously been identified as contributing to conferring higher risk. Their statistical approach analyzed single nucleotide polymorphisms (SNPs) to determine whether certain variants were responsible for this increased risk.
This analysis yielded three independent SNPs linked to higher ALL incidence and one which was present in roughly 30% of Hispanics and Latinos in the U.S., but was present in only about 1% of people of European origin. They determined that overall, children in the study with the variant located at SNP rs76880433 were 1.44 times more likely to develop ALL compared with children without that specific variant.
While more research is warranted, this newly implicated variant could lead to the development of screening tests to determine those most at risk of developing ALL, as well as potential avenues for developing new treatments for the disease.
