Abstract
Objectives: The aim of the present study was to define the potential relationship between xeroderma pigmentosum group D (XPD) Lys751Gln polymorphisms and the risk of leukemia.Methods: A comprehensive search of Pubmed, Web of Science, EBSCO, the Cochrane Library and China National Knowledge Infrastructure was conducted to identify original articles published before March 2017 concerning the association between XPD Lys751Gln polymorphisms and leukemia risk. A literature quality assessment was performed using the Newcastle-Ottawa Scale. Heterogeneity across studies was assessed using I2 statistics. Random- or fixed-effects models were used to calculate pooled odds ratios (ORs) in the presence or absence of heterogeneity, respectively. Sensitivity analysis was used to assess the influence of individual studies on the pooled estimate. Publication bias was investigated using funnel plots and Egger’s regression test. All data analyses were performed using Stata 14.0 and Revman 5.3.Results: Fourteen studies with a total of 7525 participants (2,757 patients; 4,768 controls) were included in this meta-analysis. We found that XPD Lys751Gln polymorphisms significantly increased the risk of developing leukemia in both dominant OR = 1.21, 95%CI [1.10–1.35], P ≤ 0.001) and heterozygote (OR = 1.22, 95%CI [1.09–1.36], P ≤ 0.001) model. An allele model showed a borderline significant increase in leukemia risk (OR = 1.13, 95%CI [1.00–1.27], P = 0.05). A subgroup analysis revealed a consistent association between XPD Lys751Gln polymorphisms and leukemia risk for some genetic models in Caucasian populations, adult or chronic groups, and in almost all models of childhood or acute groups.Conclusion: Our results indicate that XPD Lys751Gln polymorphism increases the risk of leukemia, especially in childhood and acute cases.
Highlights
Leukemia, a common malignant disease of the hematopoietic system (Jiang et al, 2014), can be classified on the basis of speed of disease progression and cell cytogenetics into four common subtypes: acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL) (Arber et al, 2016)
A significant increase in leukemia risk was identified in dominant (Gln/Gln + Lys/Gln vs. Lys/Lys: I2 = 24%, P < 0.001, Figure 2) and heterozygote models (Lys/Gln vs. Lys/Lys: I2 = 0%, P < 0.001, Figure 3)
Our results indicate that xeroderma pigmentosum group D (XPD) Lys751Gln polymorphism significantly increases the overall leukemia risk in dominant and heterozygote models, but not in an allele model or homozygote model
Summary
A common malignant disease of the hematopoietic system (Jiang et al, 2014), can be classified on the basis of speed of disease progression and cell cytogenetics into four common subtypes: acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL) (Arber et al, 2016). The etiology and XPD Lys751Gln Polymorphism and Leukemia Risk mechanisms underlying of leukemogenesis are still unclear, radiation, smoking, obesity and exposure to chemical carcinogens are considered high risk factors (Larsson and Wolk, 2008; Fircanis et al, 2014; Malagoli et al, 2016; Nikkila et al, 2016). Only a small proportion of people exposed to these risks develops leukemia, suggesting that hereditary factors may play a critical role in leukemia carcinogenesis (Li et al, 2016; Huang and Ovcharenko, 2017). Decreased efficiency of DNA repair is considered a crucial event in carcinogenesis (Hoeijmakers, 2001). A series of studies revealed that reduced DNA repair, leading to chromosomal aberrations and genomic instability, is a major contributor to the pathogenesis of leukemia (DasGupta et al, 2000; Esposito and So, 2014). Because of the biological significance of XPD, XPD polymorphisms have been extensively studied in different malignant diseases, such as pancreatic (Wu et al, 2017), colorectal (Ni et al, 2014) and gallbladder (Srivastava et al, 2010) cancers
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