The Effect of XPD Polymorphisms on Digestive Tract Cancers Risk: A Meta-Analysis

Abstract

BackgroundThe Xeroderma pigmento-sum group D gene (XPD) plays a key role in nucleotide excision repair. Single nucleotide polymorphisms (SNP) located in its functional region may alter DNA repair capacity phenotype and cancer risk. Many studies have demonstrated that XPD polymorphisms are significantly associated with digestive tract cancers risk, but the results are inconsistent. We conducted a comprehensive meta-analysis to assess the association between XPD Lys751Gln polymorphism and digestive tract cancers risk. The digestive tract cancers that our study referred to, includes oral cancer, esophageal cancer, gastric cancer and colorectal cancer.MethodsWe searched PubMed and EmBase up to December 31, 2012 to identify eligible studies. A total of 37 case-control studies including 9027 cases and 16072 controls were involved in this meta-analysis. Statistical analyses were performed with Stata software (version 11.0, USA). Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association.ResultsThe results showed that XPD Lys751Gln polymorphism was associated with the increased risk of digestive tract cancers (homozygote comparison (GlnGln vs. LysLys): OR = 1.12, 95% CI = 1.01–1.24, P = 0.029, P heterogeneity = 0.133). We found no statistical evidence for a significantly increased digestive tract cancers risk in the other genetic models. In the subgroup analysis, we also found the homozygote comparison increased the susceptibility of Asian population (OR = 1.28, 95% CI = 1.01–1.63, P = 0.045, P heterogeneity = 0.287). Stratified by cancer type and source of control, no significantly increased cancer risk was found in these subgroups. Additionally, risk estimates from hospital-based studies and esophageal studies were heterogeneous.ConclusionsOur meta-analysis suggested that the XPD 751Gln/Gln genotype was a low-penetrate risk factor for developing digestive tract cancers, especially in Asian populations.

Exploratory analysis of ERCC2 DNA methylation in survival among pediatric medulloblastoma patients

“…One essential gene in the NER pathway is the excision repair cross-complementation group 2 ( ERCC2 ), found on the q arm of chromosome 19 and codes for the xeroderma pigmentosum group D (XPD) protein. Previous studies have identified a link between ERCC2 genetic variation and cancer risk, including breast, prostate, gastric, lung, head and neck, and esophageal cancer, 37–43 as well as survival among cancers treated with platinum-based regimens. 8–12 At least a portion of the association between ERCC2 and the response to platinum chemotherapy appears to be explained by differences in the expression of XPD.…”

XPD–The Lynchpin of NER: Molecule, Gene, Polymorphisms, and Role in Colorectal Carcinogenesis

“…Their meta-analysis concluded that XPD Lys/Gln and XPD Gln/Gln genotypes had had 1.3- and 1.6-fold increased risk of developing cancer as compared with the wild XPD Lys/Lys genotype, respectively. Similarly, another meta-analysis of 37 case-control studies (including 9,027 cases and 16,072 controls) by Du et al ( 2014 ) suggested that the XPD 751Gln/Gln genotype was a low-penetrate risk factor for developing digestive tract cancers, especially in Asian populations.…”

“…A large number of epidemiological studies have been carried out recently to understand the effects and role of XPD SNPs on the modulation of risk of CRC; while some studies found a significant association between the two (Skjelbred et al, 2006 ; Gan et al, 2012 ; Huang et al, 2013 ; Procopciuc and Osian, 2013 ; Rezaei et al, 2013 ; Paszkowska-Szczur et al, 2015 ) others failed to link them (Yeh et al, 2005 ; Zhang et al, 2011 , 2014 ; Du et al, 2014 ; Moghtit et al, 2014 ).…”

XAB2 TagSNP Is Associated with the Risk of Gastric Cancer in Chinese Population: A Case–Control Study

“…The functional polymorphisms in key components of NER could affect DNA repair capacity and further contribute to the development of various cancers. For example, ERCC1 rs11615 and rs17655 polymorphisms were associated with an increased risk of laryngeal cancer [ 13 ] and XPD Lys751Gln variant was associated with an increased risk of digestive tract cancer [ 14 ].…”