• Journal of Photoscience
• /
• 제9권2호
• /
• pp.182-185
• /
• 2002

There are 3 UV DNA repair endonuclease activities in mammalian cells that cleave UV -irradiated DNA. Interestingly, mammalian UV endonuclease III with MW of 26.7kD has a lyase activity on AP sites. It also cleaves the phosphodiester bond within a cyclobutane pyrimidine dimer. Genomic analysis of human repair endonuclease III gene revealed that this gene has 100% sequence identity with ribosomal protein S3 (rpS3). Therefore, rpS3 seems to function both in translation and in DNA repair. This gene of about 6.1 kb contains 6 introns and 7 exons, and the first and fifth introns of human rpS3 gene contain functional U15 small nucleolar (sno) RNAs which appear to be involved in ribosome assembly. It is to be noted that the column profile of the endonuclease activity of rpS3 appears to be altered in Xeroderma Pigmentosum (XP) group D cells compared to normal cells indicating that this protein is involved in XP disease as well. XP is a human disease characterized by high sensitivity of skin by UV- or sun-light irradiation and by high frequency of developing skin cancers. We also report here that rpS3 protein is involved in other cellular functions.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권1호
• /
• pp.145-148
• /
• 2013

Aim: Individual differences in chemosensitivity and clinical outcome of non-small-cell lung cancer (NSCLC) patients may be induced by host inherited factors. We investigated the impact of XPD Arg156Arg, XPD Asp312Asn, XPD Asp711Asp and XPD Lys751Gln gene polymorphisms on the efficacy of platinum-based chemotherapy in NSCLC patients. Methods: A total of 496 were consecutively selected from the Affiliated Hospital of Nantong University between Jan. 2003 and Nov. 2006, and all patients were followed-up until Nov. 2011. The genotyping of XPD Arg156Arg, XPD Asp312Asn, XPD Asp711Asp and XPD Lys751Gln was conducted by duplex polymerase-chain-reaction with the confronting-two-pair primer methods. Results: Individuals with XPD 312 C/T+T/T and XPD 711 C/T+T/T exhibited poor responses to chemotherapy when compared with the wild-type genotype, with adjusted ORs(95% CI) of 0.67(0.38-0.97) and 0.54(0.35-0.96), respectively. Cox regression showed the median PFS and OS of patients of XPD 312 C/T+T/T genotype and XPD 711 C/T+T/T genotype to be significantly lower than those with wild-type homozygous genotype. Conclusion: We found polymorphisms in XPD to be associated with response to platinum-based chemotherapy in NSCLC, and our findings provide information for therapeutic decisions for individualized therapy.

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권7호
• /
• pp.3299-3303
• /
• 2012

Objective: To investigate the association between xeroderma pigmentosum group D (XPD) Asp312Asn polymorphism and esophageal cancer (EC) susceptibility by meta-analysis. Methods: We searched PubMed up to April 9th, 2012, to identify relevant papers, and 8 published case-control studies including 2165 EC patients and 3141 healthy controls were yielded. Odds ratios (ORs) with relevant 95% confidence intervals (CIs) were applied to assess the association between XPD Asp312Asn polymorphism and EC susceptibility with the Comprehensive Meta-Analysis software, version 2.2. Results: Overall, the meta-analysis results suggested the XPD Asp312Asn polymorphism to be significantly associated with EC susceptibility [(Asn/Asn+Asp/Asn) vs. Asp/Asp: OR=1.20, 95%CI=1.05-1.36, p=0.01; and Asp/Asn vs. Asp/Asp: OR=1.15, 95%CI =1.01-1.31, p=0.04]. In the subgroup analysis by ethnicity and cancer type, significantly associations were found for Caucasian populations [(Asn/Asn+Asp/Asn) vs. Asp/Asp: OR=1.26, 95%CI =1.08-1.47, p<0.001; Asp/Asn vs. Asp/Asp: OR=1.19, 95%CI =1.02-1.40, p=0.03] and esophageal squamous cell carcinoma [(Asn/Asn+Asp/Asn) vs. Asp/Asp: OR=1.19, 95%CI=1.01-1.41, p=0.04]. There was no heterogeneity and no publication bias existed. Conclusions: This meta-analysis shows that the XPD Asp312Asn polymorphism may be a risk factor for developing EC, especially for Caucasian populations and esophageal squamous cell carcinoma.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권21호
• /
• pp.9347-9353
• /
• 2014

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 meta-analysis 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.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권22호
• /
• pp.9699-9706
• /
• 2014

Background: The predictive value of the xeroderma pigmentosum group D (XPD) Lys751Gln polymorphism regarding clinical outcomes of patients with colorectal cancer (CRC) receiving oxaliplatin-based chemotherapy has been evaluated in numerous published studies, but the results remain inconclusive. Therefore, we performed a meta-analysis to determine the precise role of the XPD Lys751Gln polymorphism in this clinical situation and optimize individual chemotherapy. Materials and Methods: A multiple search strategy was used to identify eligible studies. Pooled odds ratios (ORs), generalized odds ratio (ORG) and their 95% confidence intervals (CIs) were used to estimate the objective response, while hazard ratios (HRs) with 95%CIs were used for progression-free survival (PFS) and overall survival (OS). Results: A total of 17 studies including 2,286 patients met the inclusion criteria. Overall, the XPD 751Gln allele was associated with a non-significant reduced objective response to oxaliplatin-based chemotherapy in all patients or in the Asian and Caucasian subgroups. However, poor PFS and OS of CRC patients treated with oxaliplatin-based regimens were significantly related to the XPD 751Gln allele in the dominant model (PFS: HR=2.10, 95%CI: 1.65-2.67; OS: HR=3.18, 95%CI: 1.57-6.47). On stratified analysis by ethnicity, these relationships were more pronounced in Asians (PFS: HR=2.49, 95%CI: 1.79-3.47; OS: HR=5.25, 95%CI: 3.46-7.94) than in Caucasians (PFS: HR=1.73, 95%CI: 1.22-2.46; OS: HR=1.78, 95%CI: 1.06-2.99). Conclusions: The XPD Lys751Gln polymorphism may have prognostic value in patients with CRC undergoing oxaliplatin-based chemotherapy.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권1호
• /
• pp.231-236
• /
• 2013

Background: Published data regarding the association between xeroderma pigmentosum group D (XPD) Lys751Gln and Asp312Asn polymorphisms and gastric cancer susceptibility havew been inconclusive. This meta-analysis was therefore performed toobtain a more precise estimation of any relationship. Materials and Methods: A comprehensive literature search was conducted to identify all case-control studies of Lys751Gln and Asp312Asn polymorphisms and susceptibility to gastric cancer. Summary odds ratios (ORs) and its 95% confidence intervals (95% CIs) were calculated using a random-effects model with the software STATA (version10.0). Results: A total of 12 case-control studies including 3,147 cases and 4,736 controls were included. Overall, no significant associations were found in some models (for Lys751Gln: Lys/Gln vs Lys/Lys: OR=1.144, 95% CI=0.851-1.541, Gln/Gln vs Lys/Lys: OR=1.215, 95% CI = 0.740-1.955, dominant model: OR=1.137, 95% CI=0.818-1.582; recessive model: OR=1.123, 95% CI=0.765-1.650; for Asp312Asn: Asp/Asn vs Asp/Asp: OR=1.180, 95% CI=0.646-2.154, dominant model: OR=1.380, 95% CI = 0.812-2.346), but significantly elevated susceptibility was found for Asp312Asn polymorphism in some models (Asn/Asn vs Asp/Asp: OR=2.045, 95% CI=1.254-3.335, recessive model: OR=1.805, 95% CI =1.219-2.672), for the additive model, the XPD Lys751Gln and Asp312Asn polymorphisms were not significantly associated with gastric cancer susceptibility. In stratified analyses, significantly elevated susceptibility was found for some models in the Chinese population. Conclusion: This meta-analysis suggested the XPD Asp312Asn polymorphism might be a potential biomarker of gastric cancer susceptibility in overall population, while both XPD Lys751Gln and Asp312Asn polymorphisms might be risk factors of gastric cancer susceptibility in Chinese.