Genome-wide association study of childhood acute lymphoblastic leukemia in Korea
Introduction
Acute lymphoblastic leukemia (ALL) is the most common malignancy in childhood, accounting for 30% of all childhood cancers [1]. The etiology of childhood ALL is mostly unknown, although infections in the first years of life and some environmental factors such as ionizing radiation and parental alcohol and tobacco use could play a causative role in ALL [2], [3], [4].
ALL is known to result from an accumulation of mutations in tumor suppressor genes and oncogenes, and genetic alterations affecting several chromosomes [5], [6], [7], [8], [9]. Although common genetic variations may play a role in determining individual susceptibility of leukemia development in children, limited studies have evaluated the association between genetic polymorphisms in candidate genes such as CYP, GST, NAT, MTHFR, NQO1, XRCC1, MDR1, cyclin D1, and CCND1 and childhood ALL risk [1], [10], [11], [12].
Given that investigation of a single enzyme (pathway) and/or a single genotype might not be sufficient to explain the etiology of childhood leukemia [11], a genome-wide approach may add to comprehensive knowledge about genetic susceptibility to childhood ALL.
In this context, we conducted a genome-wide association study (GWAS) to identify genetic variations associated with childhood ALL in our Korean Childhood Leukemia Study.
Section snippets
Subjects
The detailed information on selection criteria of the subjects and data collection was described elsewhere [13]. Histologically confirmed incident childhood ALL cases (n = 201) aged 0–18 years old were recruited from three teaching hospitals located in Seoul, Korea, between May 2003 and August 2008. Non-cancer controls (n = 558) aged 0–18 years old without medical history of childhood cancer were recruited from the Department of Pediatrics of the same hospitals. Participation rate was approximately
Results
There was no significant difference of the selected characteristics between case and control group except for birth weight: higher birth weight was associated with increased risk of childhood ALL (3.25–3.70 vs. ≤3.25 kg: OR = 6.04, 95% CI = 2.04–17.01; >3.70 vs. ≤3.25 kg: OR = 4.56, 95% CI = 1.53-13.52; Ptrend = 0.001, data not shown). Fig. 1 shows P values on a logarithmic scale from trend tests for 681,931 selected variants.
Among the 681,931 SNPs, 57,173 SNPs in 7,791 genes had a Ptrend < 0.05 from
Discussion
In our genome-wide association study, 6 novel SNPs in 4 genes in childhood ALL using Affymetrix SNP Array 6.0 platform were associated with childhood ALL (HAO1: rs6140264; EPB41L2: rs9388856, rs9388857, and rs1360756, C2orf3: rs12105972; MAN2A1: rs3776932).
Although our observation should be interpreted cautiously due to limited biological plausibility for the observed association between those SNPs and childhood ALL risk, we note that erythrocyte membrane protein band 4.1-like 2 (EPB41L) plays
Conflict of interest
The authors declare no conflict of interest.
Acknowledgements
The authors thank all patients and their parents who consented to participate in genetics study related to leukemia.
This study was supported by a grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, R.O.K. (AO30001) and a grant No. R31-2008-000-10103-0 from the WCU project of the MEST and the NRF.
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High-resolution melting analyses for genetic variants in ARID5B and IKZF1 with childhood acute lymphoblastic leukemia susceptibility loci in Taiwan
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