Association of XPG gene rs751402 polymorphism with gastric cancer risk: a meta-analysis in the Chinese population

Background: Previous studies have revealed a conflicting relationship of xeroderma pigmentosum group G (XPG) gene polymorphism with gastric cancer (GC) risk. To our knowledge, this is the first meta-analysis to investigate the association between rs751402 mutation located on the XPG promoter region and GC risk. Methods: We undertook a meta-analysis by identifying relevant articles from the PubMed, Web of Science and China National Knowledge Infrastructure (CNKI) databases on February 28, 2017. By pooling 9 eligible studies, 3,539 GC cases and 3,948 controls were included. The pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated using the fixed-effects or random-effects model depending on the existence of heterogeneity across studies. The population attributable risk (PAR%) was estimated to better understand the public health risk. Results: All included studies had been conducted in China. Significant associations were found between the XPG rs751402 polymorphism and the risk of GC (TT vs. CC: OR = 1.43, 95% CI, 1.11-1.84; CT vs. CC: OR = 1.15, 95% CI, 1.04-1.26; dominant model: OR = 1.17, 95% CI, 1.07-1.29; recessive model: OR = 1.30, 95% CI, 1.05-1.62; T vs. C: OR = 1.18, 95% CI, 1.06-1.32). The estimated PAR% was about 4.9%-8.8%. Funnel plots did not reveal any potential publication bias. The sensitivity analyses showed that the results were relatively robust. Conclusions: This meta-analysis indicates that the XPG rs751402 polymorphism may be a risk factor for GC in the Chinese population.

Regulation of transcription elongation by the XPG-TFIIH complex is implicated in Cockayne syndrome

XPGis a causative gene underlying the photosensitive disorder, xeroderma pigmentosum group G, and is involved in nucleotide excision repair. Here, we show that XPG knockdown represses epidermal growth factor (EGF)-inducedFOStranscription at the level of transcription elongation with little effect on EGF signal transduction. XPG interacted with transcription elongation factors in concert with TFIIH, suggesting that the XPG-TFIIH complex serves as a transcription elongation factor. The XPG-TFIIH complex was recruited to promoter and coding regions of both EGF-induced (FOS) and housekeeping (EEF1A1) genes. Further, EGF-induced recruitment of RNA polymerase II and TFIIH toFOSwas reduced by XPG knockdown. Importantly, EGF-inducedFOStranscription was markedly lower in XP-G/CS cells expressing truncated XPG than in control cells expressing wild-type (WT) XPG, with less significant decreases in XP-G cells with XPG nuclease domain mutations. In corroboration of this finding, both WT XPG and a missense XPG mutant from an XP-G patient were recruited toFOSupon EGF stimulation, but an XPG mutant mimicking a C-terminal truncation from an XP-G/CS patient was not. These results suggest that the XPG-TFIIH complex is involved in transcription elongation, and that defects in this association may partly account for Cockayne syndrome in XP-G/CS patients.