Comprehensive Assessment of Associations between ERCC2 Lys751Gln/Asp312Asn Polymorphisms and Risk of Non-Hodgkin Lymphoma

Abstract

Background: Excision repair crossing-complementing group 2 (ERCC2), also called xeroderma pigmentosum complementary group D (XPD), plays a crucial role in the nucleotide excision repair (NER) pathway. Previous epidemiological studies have reported associations between ERCC2 polymorphisms and non-Hodgkin lymphoma (NHL) risk, but the results have remained controversial. Materials and Methods: We conducted this metaanalysis based on eligible case-control studies to investigate the role of two ERCC2 polymorphisms (Lys751Gln and Asp312Asn) in determining susceptibility to NHL. Ten case-control studies from several electronic databases were included in our study up to August 14, 2014. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using fixed-or random-effects models to estimate the association strength. Results: The combined results based on all studies did not show any association between Lys751Gln/Asp312Asn polymorphisms and NHL risk for all genetic models. Stratified analyses by histological subtype and ethnicity did not indicate any significant association between Lys751Gln polymorphism and NHL risk. However, a significant reduced risk of NHL was found among population-based studies (Lys/Gln versus Lys/Lys: OR=0.87, 95% CI=0.77-0.99, P=0.037) but not hospital-based studies. As for Asp312Asn polymorphism, there was no evidence for the association between this polymorphism and the risk of NHL in all subgroup analyses. Conclusions: This meta-analysis suggests that there may be no association between Lys751Gln/Asp312Asn polymorphism and the risk of NHL and its two subtypes, whereas ERCC2 Lys751Gln heterozygote genotype may provide protective effects against the risk of NHL in population-based studies. Therefore, large-scale and well-designed studies are needed to clarify the effects of haplotypes, gene-gene, and gene-environment interactions on these polymorphisms and the risk of NHL and its different histological subtypes in an ethnicity specific population.

Association of ERCC2 Gene Polymorphisms with Susceptibility to Diffuse Large B-Cell Lymphoma

“…Meanwhile, El-Din et al found no significant association between rs1799793 SNP and DLBCL susceptibility in an Egyptian population, despite A allele carriers having a higher trend for DLBCL [ 27 ]. Inversely, a recent meta-analysis study showed that rs1799793 was negatively correlated with DLBCL risk under Asn (A) vs. Asp (G) genetic model [ 28 ]. These differences might be caused by differences in ethnicity or regions.…”

“…In this study, no significant association has been discovered between rs13181 genotypes and DLBCL risk; while an approximately 1.820 times elevated DLBCL risk was associated with rs13181 C allele. El-Din et al indicated that rs13181 CC genotype carriers had higher susceptibility for DLBCL, but the association was not significant [ 28 ]. However, Worrillow et al demonstrated that rs13181 CC genotype was significantly associated with reduced risk for DLBCL in an English population [ 26 ].…”

“…However, Worrillow et al demonstrated that rs13181 CC genotype was significantly associated with reduced risk for DLBCL in an English population [ 26 ]. In addition, meta-analysis studies also failed to find a significant association between this SNP and DLBCL risk [ 23 , 28 ].…”