Germline Variants Linked to Risk of Childhood Leukemia

Inherited variation appears to contribute to risk of ALL, development of some particular subtypes

TUESDAY, Aug. 25 (HealthDay News) -- Inherited genetic variants appear to play a role both in the risk of childhood acute lymphoblastic leukemia (ALL) and the development of specific types of the disease, according to research published online Aug. 16 in Nature Genetics.

Lisa R. Trevino, Ph.D., of the St. Jude Children's Research Hospital in Memphis, Tenn., and colleagues discuss the results of their genome-wide association study. The researchers analyzed germline DNA from 317 children of European descent from a discovery cohort and identified 18 single-nucleotide polymorphisms (SNPs) with an allele frequency that differed significantly between cases and controls. They then compared the frequency of these SNPs with the four most common subtypes of ALL, and found six of the SNPs differentiated the subtypes. The comparison was repeated with a validation cohort of 124 children of European descent.

The researchers discovered that two SNPs in the ARID5B gene discriminated B-hyperdiploid ALL from the other subtypes; this type responds better to methotrexate chemotherapy than other subtypes. Three of the 18 SNPs that were associated with ALL were localized to the IKZF1 and DDC genes and distinguished T-cell from B-lineage ALL in the discovery cohort.

"Our findings indicate that inherited genetic variation contributes to the risk of childhood ALL and is likely to contribute to the development of some specific ALL subtypes. The data further suggest that the same genetic variation that predisposes to B-hyperdiploid ALL may underlie the superior response of this subtype to chemotherapy. Thus, genomic variation may affect not only disease risk but treatment outcome as well," the authors conclude.

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