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

Abstract

<b>Background:</b> Excision repair crossing-complementing group 2 (ERCC2), also called xeroderma pigmentosumcomplementary group D (XPD), plays a crucial role in the nucleotide excision repair (NER) pathway. Previousepidemiological studies have reported associations between ERCC2 polymorphisms and non-Hodgkin lymphoma(NHL) risk, but the results have remained controversial. Materials and <br/><b>Methods</b>: We conducted this metaanalysisbased on eligible case-control studies to investigate the role of two ERCC2 polymorphisms (Lys751Glnand Asp312Asn) in determining susceptibility to NHL. Ten case-control studies from several electronic databaseswere 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. <br/><b>Results</b>: The combinedresults based on all studies did not show any association between Lys751Gln/Asp312Asn polymorphisms and NHLrisk for all genetic models. Stratified analyses by histological subtype and ethnicity did not indicate any significantassociation between Lys751Gln polymorphism and NHL risk. However, a significant reduced risk of NHL wasfound among population-based studies (Lys/Gln versus Lys/Lys: OR=0.87, 95% CI=0.77-0.99, P=0.037) but nothospital-based studies. As for Asp312Asn polymorphism, there was no evidence for the association between thispolymorphism and the risk of NHL in all subgroup analyses. <br/><b>Conclusions</b>: This meta-analysis suggests that theremay 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 inpopulation-based studies. Therefore, large-scale and well-designed studies are needed to clarify the effects ofhaplotypes, gene-gene, and gene-environment interactions on these polymorphisms and the risk of NHL and itsdifferent histological subtypes in an ethnicity specific population.