New Genetic Variations Found to Elevate Risk of Acute Lymphoblastic Leukemia in Hispanic Children

Researchers have discovered new genetic variations that increase the susceptibility of Hispanic children to acute lymphoblastic leukemia (ALL), the most common childhood cancer, according to a study published in Blood.

It has been established that Hispanics are disproportionately affected by ALL, with high incidence and inferior survival compared with other ethnicities. The study, led by scientists from St. Jude Children’s Research Hospital, highlights a potential genetic basis for this disparity.

In the study, the researchers identified genetic variations in a gene called ERG, a transcription factor that is also mutated in the leukemic cells of some patients with ALL, which contributes to an elevated risk of the disease.

To find this, they performed a genome-wide association study in 940 Hispanic children with ALL and 681 children of similar backgrounds without an ALL diagnosis. Hispanic ethnicity was defined as having more than 10% Native American gene variations, as well as having more Native American than African gene variations.

The researchers identified the novel susceptibility in the ERG gene, discovering high-risk variations in ERG that were associated with a 1.56-fold increased risk of ALL in Hispanic children. In addition, the study also confirmed previous findings that high-risk genetic variations in ARID5B, GATA3, and PIP4K2A were common in Hispanic children and were associated with an increased risk of developing ALL.

Children with the highest percentage of Native American ancestry were at the highest risk of developing ALL, whereas children with the lowest percentage were least likely to develop the disease. Additionally, African American children with high-risk ERG variations showed no significant increased risk of ALL and children of European ancestry had just a 12% elevated risk, according to the study.

Interestingly, the ALL cases with germline ERG risk variations were significantly less likely to have somatic variations, the researchers noted. The study showed that Hispanic patients with ALL rarely had both ERG germline and somatic variations at the same time.

Not only were the high-risk EGR variants more common in Hispanic children, but the study authors found that they also had a stronger effect in this population. They noted that further research is needed to understand the mechanism involved.

“The more we understand the biology behind these disparities, the more likely we are to develop more effective therapies for different patient populations or better methods to track and monitor disease risk,” study author Jun J. Yang, PhD, an associate member of the Hematological Malignancies Program of the St. Jude Comprehensive Cancer Center and in the Pharmaceutical Sciences Department, said in a press release about the findings.

References

Qian M, Xu H, Perez-Andreu V, et al. Novel susceptibility variants at the ERG locus for childhood acute lymphoblastic leukemia in Hispanic. Blood. 2019. doi: https://doi.org/10.1182/blood-2018-07-862946

Genetic variations in a fourth gene linked to elevated leukemia risk in Hispanic children [news release]. St. Jude Children’s Research Hospital. https://www.stjude.org/media-resources/news-releases/2019-medicine-science-news/genetic-variations-in-a-fourth-gene-linked-to-elevated-leukemia-risk-in-hispanic-children.html. Accessed February 14, 2019.