The Association Between XRCC1 Arg399Gln Polymorphism and Risk of Leukemia in Different Populations: A Meta-Analysis of Case-Control Studies

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The single-nucleotide polymorphism (SNP) XRCC1 Arg399Gin is a risk factor for pediatric lymphoblastic leukemia in Asian persons, a study published in the journal OncoTargets and Therapy has shown.

Although previous studies have evaluated associations between the XRCC1 Arg399Gin SNP and leukemia susceptibility, the findings have been inconsistent. Therefore, researchers sought to conduct a meta-analysis to assess the association of the SNP and leukemia risk in different populations in relevant studies. A total of 21 articles were analyzed. Of those, 5 focused on acute myeloid leukemia (AML), 10 focused on acute lymphocytic leukemia (ALL), 3 focuses on chronic lymphocytic leukemia (CLL), 2 focused on chronic myelogenous leukemia (CML), and 1 focused on both AML and CML.

Results showed that the XRCC1 Arg399Gin SNP was associated with increased childhood risk of ALL among Asians, but there was no association among Caucasians or those of mixed race. Researchers also found no association between the SNP and childhood CML or CLL risk among Caucasians, which was the primary study population for these 2 diseases. The authors speculate that the development of chronic leukemia may be greatly influenced by environmental factors with limited influence from the SNP.

The authors note, however, that large-scale studies are necessary to confirm these results.

OncoTargets and Therapy
OncoTargets and Therapy

Background: Associations between Arg399Gln single-nucleotide polymorphism (SNP) in the XRCC1gene and leukemia susceptibility have been studied extensively, however, the results are inconsistent. The aim of this study was to determine these associations using meta-analytical methods.
Methods: A meta-analysis was performed to examine the associations between XRCC1 Arg399Gln SNP and leukemia risk. A literature search of PubMed and Web of Science databases was conducted to identify relevant studies published up to March 10, 2015. The references of the retrieved articles were also screened. All the statistical analyses were conducted using Review Manager software.
Results: The XRCC1 Arg399Gln SNP was found to be associated with increased childhood risk of acute lymphoblastic leukemia among Asians under the dominant (odds ratio [OR] 2.11, 95% confidence interval [CI] 1.50–2.97, P<0.0001), allele contrast (OR 1.72, 95% CI 1.33–2.23,P<0.0001), and homozygote contrast (OR 2.34, 95% CI 1.25–4.36, P=0.008) models. However, no association was found in Caucasians between the SNP and risk of either chronic myeloid leukemia or chronic lymphocytic leukemia under any contrast model.
Conclusion: The findings of the current meta-analysis indicate that the XRCC1 Arg399Gln SNP is a risk factor for childhood lymphoblastic leukemia in Asians.

Keywords: Arg399Gln, AML, ALL, CML, CLL, susceptibility


Leukemia is a malignant neoplasm of blood-forming tissues1 that can be classified into the following four groups according to the cell type and growth rate: acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic myeloid leukemia (CML), and chronic lymphocytic leukemia (CLL).2 Despite numerous studies on leukemogenesis, the mechanism underlying the development of these cancers is yet to be fully elucidated.

DNA repair pathways play a vital role in maintaining genetic integrity, and it is becoming clear that defects in repair pathways are connected to many different types of diseases, including leukemia.3 It has been reported that impaired DNA repair may be associated with increased susceptibility to human cancers.4 The XRCC1 gene is one of the most important DNA repair genes, and plays a key role in the process of base excision repair.1 XRCC1 single-nucleotide polymorphism (SNP) Arg399Gln at codon 399 has been extensively examined and is associated with diminished capacity to remove DNA adducts, causing DNA damage due to oxidation.5 Therefore, the Arg399Gln SNP may contribute to leukemia.

Studies of the association between XRCC1 SNPs and leukemia have produced conflicting findings, possible reasons for which include differences in ethnicity and sample size. The aim of the present meta-analysis was to obtain a more accurate picture with regard to the role of the XRCC1 Arg399Gln SNP in the risk of leukemia.  

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