Leukemia is one of the most common cancers among children, affecting around 55,000 globally each year. The most prevalent type, Acute Lymphoblastic Leukemia (ALL), has known risk factors, with research indicating that certain genetic variants may contribute to the likelihood of developing the disease.

 

In the United States, children of Hispanic descent have a 30-40% higher risk of leukemia compared to other populations. Researchers at the Keck School of Medicine at USC recently identified a genetic variant linked to this increased risk, primarily found among individuals of Latino/Hispanic ancestry. This variant is associated with a 1.4% higher chance of developing ALL.

 

The ancestry of Hispanic/Latino populations in the U.S. typically includes European, African, and Indigenous American roots. The risk variant discovered is specifically linked to Indigenous American ancestry, where it may have conferred a genetic advantage historically.

 

The variant is located in the IKZF1 gene, which plays a role in ALL by influencing the development of B-cells—white blood cells affected by the disease. The IKZF1 gene is found on chromosome 7 (7p12.2) and includes eight exons that code for 519 amino acids.

 

Using data from the California Cancer Records Linkage Project, researchers examined single nucleotide polymorphisms (SNPs) in the IKZF1 gene to identify those associated with ALL risk. Three independent SNPs were linked to an elevated risk, including rs76880433, which appears in roughly 30% of Hispanic/Latino individuals in the U.S. but in less than 1% of those of primarily European descent. Although the absolute risk of ALL remains low across all racial and ethnic groups, children carrying this gene variant have a 1.44 times higher likelihood of developing ALL compared to those without it.

 

Researchers also found that the IKZF1 gene struggles to express effectively in individuals with the risk variant. This compromised expression disrupts B-cell maturation, leaving cells in an immature state and thus more susceptible to mutations that can lead to ALL.

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