Genetic Susceptibility Loci ID'd for Leukemia in Children
Findings consistent for ethnically diverse children with acute lymphoblastic leukemia
WEDNESDAY, March 27 (HealthDay News) -- For children, inherited genetic variants correlate strongly with susceptibility to acute lymphoblastic leukemia (ALL), according to a study published online March 19 in the Journal of the National Cancer Institute.
Heng Xu, Ph.D., from St. Jude Children's Research Hospital in Memphis, Tenn., and colleagues performed a genome-wide association study in a multiethnic group of 1,605 children with ALL and 6,661 control subjects. Results were validated in three replication series of 845 case subjects and 4,316 control subjects.
The researchers identified a novel ALL susceptibility locus at 10p12.31-12.2 (BMI1-PIP4K2A, rs7088318), which was independently replicated in European-Americans, African-Americans, and Hispanic-Americans. Four known ALL susceptibility loci (ARID5B, IKZF1, CEBPE, and CDKN2A/2B) were also validated. Across ethnicities, the correlations with ARID5B, IKZF1, and BMI1-PIP4K2A were consistent, with multiple independent signals seen at IKZF1, and BMI1-PIP4K2A. In parallel with ethnic differences in ALL incidence, the frequency of ARID5B and BMI1-PIP4K2A variants differed by ethnicity. Age was suggested to have a modifying effect on the genetic predisposition to ALL. There was a cumulative effect observed, with ARID5B, IKZF1, CEBPE, and BMI1-PIP4K2A variants conferring a strong predisposition to ALL; children carrying six to eight copies of risk alleles had a nine-fold higher relative risk for ALL compared to those carrying zero to one risk allele.
"These findings indicate strong associations between inherited genetic variation and ALL susceptibility in children and shed new light on ALL molecular etiology in diverse ancestry," write the authors.