Closing in On Why Kids Get Cancer

Acute lymphoblastic leukemia risks higher in children who inherit certain altered genes

/ Author:  / Reviewed by: Joseph V. Madia, MD

(RxWiki News) With some forms of cancer, race matters. New research may explain why Hispanic children are more prone to a type of blood cancer.

Inheriting four specific gene variations dramatically increased children’s risk of developing acute lymphoblastic leukemia (ALL), a new study has found.

This research also uncovered that Hispanic children were more likely to inherit two of those altered risk genes than children of European or African descent.

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Jun J. Yang, PhD, an assistant member of the St. Jude Department of Pharmaceutical Sciences, was the senior author of this study.

This was one of the largest multi-ethnic ALL studies ever conducted, involving 2,450 pediatric ALL patients and 10,977 individuals without the disease from a variety of racial and ethnic backgrounds.

ALL is the most common type of childhood leukemia, and is diagnosed in about 3,000 youngsters in the US every year. The blood cancer that attacks certain immune cells is one of the more curable childhood cancers. Most cases of ALL are seen in children 2 to 4 years old.

For this study, researchers used an automated system to check each individual’s DNA for 709,059 gene variations.

Since genes are inherited from both parents, a child has the possibility of inheriting two copies of the four risk genes, for a total of eight copies.

Researchers found that children who inherited more than five copies of the variant genes had a nine-fold higher risk of developing childhood ALL compared to those who inherited none or only one copy.

Dr. Yang explained that the absolute risk for a particular child of developing ALL is quite low. "ALL is a complex disease that likely involves many genes," he said.

"The discoveries we are reporting in this paper are an important step forward in terms of understanding why children develop ALL in the first place, particularly for those with African or Hispanic ethnicity. However, this is probably still just a small part of the complete picture."

Previous St. Jude research has shown that four genetic variations are linked to pediatric ALL risks – ARID5B, IKZF1, CEBPE and CDKN2A/2B genes.

The study found Hispanic patients were more likely than others in this study to inherit high-risk versions of two of the genes – ARID5B and PIP4K2A – while black patients were less likely to have these variants.

Younger children were also more vulnerable to the disease if they inherited these altered genes.

A trend in research has suggested that inheritance plays a role in ALL risks. Previous work, though, has only included patients of European ancestry. This study helps to explain why Hispanic children are more prone to ALL.

Ching-Hon Pui, MD, Oncology Department chair at St. Jude and co-author of the paper, told dailyRx News, "National data show that children of African ancestry have a lower risk of ALL than children of European or Hispanic ancestry. This study suggests the difference might be due in part to these high-risk variants, which are less common in children of African ancestry."

The report on this study was published March 19 in the Journal of the National Cancer Institute.

This work was supported by the National Institutes of Health, the Intramural Program of the National Cancer Institute and the American Lebanese Syrian Associated Charities. No conflicts of interest were reported.

Reviewed by: 
Review Date: 
March 19, 2013
Last Updated:
March 21, 2013