Mentor-Molecular Pathology and Clinical Research Services, Research and Development, Goregaon, Mumbai, India
Background Childhood acute lymphoblastic leukemia (ALL) is a heterogeneous genetic disease and its etiology remains poorly understood. Recent genome wide association and replication studies have highlighted speci c polymorphisms contributing to childhood ALL predispositions mostly in European populations. It is unclear if these observations generalize to other populations with a lower incidence of ALL. The current case-control study evaluated variants in ARID5B (rs7089424, rs10821936), IKZF1 (rs4132601) and CEBPE (rs2239633) genes, which appear most signi cantly associated with risk of developing childhood B-lineage ALL. Materials and Methods Using TaqMan assays, genotyping was conducted for 162 de novo B-lineage ALL cases and 150 unrelated healthy controls in India. Appropriate statistical methods were applied. Results Genotypic and allelic frequencies differed signi cantly between cases and controls at IKZF1-rs4132601 (p0.039, p0.015) and ARID5B-rs10821936 (p0.028, p0.026). Both rs10821936 (p0.019; OR 0.67; 95% CI0.47-0.94) and rs4132601 (p0.018; OR 0.67; 95%CI 0.48-0.94) were associated with reduced disease risk. Moreover, gender- analysis revealed male-speci c risk associations for rs10821936 (p0.041 CT+CC) and rs4132601 (p0.005 G allele). Further, ARID5B-rs7089424 and CEBPE-rs2239633 showed a trend towards decreased disease risk but without signi cance (p0.073; p0.73). Conclusions Our ndings provide the rst evidence that SNPs ARID5B- rs10821936 and IKZF1-rs4132601 are associated with decreased B-lineage ALL susceptibility in Indian children. Understanding the effects of these variants in different ethnic groups is crucial as they may confer different risk of ALL within different populations.