Authors:
Evans TJ, Milne E, Anderson D, De Klerk NH, Jamieson SE, Talseth-Palmer BA, et al.
Authors notes:
PLoS ONE. 2014;9(10):e110255
Keywords:
acute lymphoblastic leukemia, ARID5B gene, IKZF1 gene, single nucleotide polymorphism
Abstract:
Genome wide association studies (GWAS) have established association of ARID5B and IKZF1 variants with childhood acute lymphoblastic leukemia (ALL).
Epidemiological studies suggest that environmental factors alone appear to make a relatively minor contribution to disease risk.
The polygenic nature of childhood ALL predisposition together with the timing of environmental triggers may hold vital clues for disease etiology.
Thirteen SNPs achieved genome wide significance in the population based case/control analysis; ten annotated to ARID5B and three to IKZF1.
The most significant SNPs in these regions were ARID5B rs4245595, and IKZF1 rs1110701.
There was evidence of geneenvironment interaction for risk genotype at IKZF1, whereby an apparently stronger genetic effect was observed if the mother took folic acid or if the father did not smoke prior to pregnancy.
There were no interactions of risk genotypes with age or sex.
Our results evidence that interaction of genetic variants and environmental exposures may further alter risk of childhood ALL however, investigation in a larger population is required.
If interaction of folic acid supplementation and IKZF1 variants holds, it may be useful to quantify folate levels prior to initiating use of folic acid supplements.