Abstract
Previous genome-wide association studies (GWAS) have implicated several single nucleotide polymorphisms (SNPs) in the AT-rich interactive domain 5B (ARID5B) gene with childhood acute lymphoblastic leukemia (ALL). However, replicated studies reported some inconsistent results in different populations. Using meta-analysis, we here aimed to clarify the nature of the genetic risks contributed by the two polymorphisms (rs10994982, rs7089424) for developing childhood ALL. Through searches of PubMed, EMBASE, and manually searching relevant references, a total of 14 articles with 16 independent studies were included. Odds ratios (ORs) with 95% confidence intervals (95%CI) were calculated to assess the associations. Both SNPs rs10994982 and rs7089424 showed significant associations with childhood ALL risk in all genetic models after Bonferroni correction. Furthermore, subtype analyses of B-lineage ALL provided strong evidence that SNP rs10994982 is highly associated with the risk of developing B-hyperdiploid ALL. These results indicate that SNPs rs10994982 and rs7089424 are indeed significantly associated with increased risk of childhood ALL.
Highlights
Acute lymphoblastic leukemia (ALL), the most common malignancy in children (Linabery and Ross, 2008; Jiang et al, 2013), is a heterogeneous disease, with respect to its underlying cellular and molecular biology (Papaemmanuil et al, 2009), acquired genetic abnormalities, and social clinical responses to combination chemotherapy (Pui et al, 2004)
Hui Zeng et al studies included in the meta-analysis were selected by searching the PubMed, EMBASE databases up to May 2014 using the following keywords: “ and (AT-rich interactive domain 5B gene or ARID5B) and”
We mainly examined the overall effects for each polymorphism
Summary
Acute lymphoblastic leukemia (ALL), the most common malignancy in children (Linabery and Ross, 2008; Jiang et al, 2013), is a heterogeneous disease, with respect to its underlying cellular and molecular biology (Papaemmanuil et al, 2009), acquired genetic abnormalities, and social clinical responses to combination chemotherapy (Pui et al, 2004). Previous genome-wide association studies (GWAS) have implicated the associations of several single nucleotide polymorphisms (SNPs) in the AT-rich interactive domain 5B (ARID5B) gene with childhood ALL (Papaemmanuil et al, 2009; Trevino et al, 2009). ARID5B, the gene encoding the ARID5B protein, which located on chromosome 10q21.2, is one of the common susceptibility loci associated with childhood ALL risk (Papaemmanuil et al, 2009; Trevino et al, 2009). Many studies have evaluated the associations between ARID5B gene polymorphisms and childhood ALL risk; the results were often irreproducible, possibly due to the ethnicity-specific genetic profiles, inadequate sample size, etc. To shed some light on these inconsistencies, we sought to assess the associations of two SNPs (rs10994982, rs7089424) from ARID5B gene with risk of childhood ALL by conducting a comprehensive metaanalysis of individual participant data from all qualified studies
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