Replication analysis confirms the association of ARID5B with childhood B-cell acute lymphoblastic leukemia

Abstract

Although childhood acute lymphoblastic leukemia is the most common pediatric cancer, its etiology remains poorly understood. In an attempt to replicate the findings of 2 recent genome-wide association studies in a French-Canadian cohort, we confirmed the association of 5 SNPs [rs7073837 (P=4.2¥10 ) and rs7089424 (P=3.6¥10 -7 )] in the ARID5B gene with childhood acute lymphoblastic leukemia. We also confirmed a selective effect for B-cell acute lymphoblastic leukemia with hyperdiploidy and report a putative gender-specific effect of ARID5B SNPs on acute lymphoblastic leukemia risk in males. This study provides a strong rationale for more detailed analysis to identify the causal variants at this locus and to better understand the overall functional contribution of ARID5B to childhood acute lymphoblastic leukemia susceptibility.

Genetic markers in a multi-ethnic sample for childhood acute lymphoblastic leukemia risk

“…Most GWAS, until recently, have identified risk loci using only European-origin populations. Variant polymorphisms located within the ARID5B, IKZF1, and CEBPE genes have reported strong risk associations in multiple studies [19][20][21][22][38][39][40]. Our study provides some confirmation of previously discovered genetic markers associated with childhood ALL, which also validated our case-control set for further exploration.…”

“…The ARID5B gene is involved in transcriptional regulation during embryonic development [38]. Overexpression of the gene in particular leukemias have led some to speculate that variations within the gene may affect B-lineage development, and increase susceptibility to B-lineage leukemia [20].…”

Genetic Markers, Birth Characteristics, and Childhood Leukemia Risk

“…Most GWAS, until recently, have identified risk loci using only European-origin populations. Variant polymorphisms located within the ARID5B, IKZF1, and CEBPE genes have reported strong risk associations in multiple GWAS [34][35][36][37][55][56][57]. Our study provides some confirmation of previously discovered genetic markers associated with childhood ALL, which also validated our case-control set for further exploration.…”

“…The ARID5B gene is involved in transcriptional regulation with embryonic development [55]. Overexpression of the gene in particular acute leukemias have led some to speculate that variations within the gene may affect B-lineage development, and increase susceptibility to B-lineage leukemia [35].…”

“…A Finnish study [55] is the only other published study that looked at HFE variants in childhood leukemia. The study population only included 32 childhood ALL patients, of which 14 were male, and did not find any significant results.…”