Xeroderma Pigmentosum Group D Lys751Gln Research Articles

Association between XPD Lys751Gln polymorphism and esophageal cancer susceptibility in China: a meta-analysis based on 12 case-control studies

Abstract Many studies have analyzed the relation about xeroderma pigmentosum group D (XPD) Lys751Gln polymorphism on esophageal cancer risk; however, the results were inconclusive. The present study was designed to assess the relationship in China. We searched the relevant articles from the databases of PubMed, Springer Link, Ovid, Chinese Wanfang Database, CNKI and Chinese Biology Medicine up to December 2019. An OR with the corresponding 95%CI was adopted to evaluate this association. This meta-analysis included 12 studies with 4195 esophageal cancer cases and 4762 controls. Overall, a positive association between XPD Lys751Gln and esophageal cancer risk was found in all the analysis model (Gln vs. Lys, OR= 1.26, 95% CI= 1.14-1.44; Gln/Gln vs. Lys/Lys, OR= 1.73, 95% CI= 1.29-2.31; Gln/Gln vs. Lys/Lys + Asp/Asn, OR= 1.63, 95% CI= 1.22-2.18; Gln/Gln+ Asp/Asn vs. Lys/Lys, OR= 1.25, 95% CI= 1.13-1.39). Subgroup analyses by geographic area and source of controls were further conducted; there was no substantial change in subgroup analyses. Our study suggested that XPD Lys751Gln polymorphism could increase the risk of esophageal cancer in China. Further studies in other ethnic populations are wanted to confirm these conclusions.

Combined GSTT1 Null, GSTM1 Null and XPD Lys/Lys Genetic Polymorphisms and Their Association with Increased Risk of Chronic Myeloid Leukemia.

PurposeGlutathione S-transferases (GSTT1 and GSTM1) are instrumental in detoxification process of activated carcinogens. Nucleotide excision repair is carried out by DNA helicase encoded by xeroderma pigmentosum group D (XPD) genes and aberrations in the XPD gene predisposes to increased risk of cancer. The present study aimed to investigate GSTT1, GSTM1 and XPD polymorphisms in newly diagnosed chronic myeloid leukemia (CML) patients and to examine the association of these polymorphisms with the risk of developing CML.Patients and MethodsThis case–control study was carried out from June 2019 to August 2021 involving 150 newly diagnosed patients with CML and an equal number of randomly selected age- and sex-matched healthy individuals. A multiplex-PCR assay was used to genotype GSTT1 null and GSTM1 null polymorphisms. XPD gene polymorphism was detected by PCR-RFLP using predesigned gene-specific primers.ResultsGSTT1 and GSTM1 null polymorphisms were detected in 42.7% and 61.3% of cases, respectively, compared to 18% and 35.3% for controls. The combination of both GST null polymorphisms revealed a significant association with CML. Frequencies of XPD Lys751Gln genotypes in cases were 62.7% heterozygous Lys/Gln, 24% homozygous Lys/Lys and 13.3% homozygous Gln/Gln, while in the controls were 74.7%, 20%, and 5.3%, respectively. Significant differences were also noted regarding the combination of GSTT1/GSTM1 null with XPD Lys/Lys, and GSTM1 null with XPD Lys/Lys.ConclusionIn conclusion, GSTT1 null, GSTM1 null and XPD polymorphisms showed positive association with the risk of development of CML. Furthermore, age and gender did not exhibit any association with the studied polymorphisms, while CML phases were associated with GSTT1 null polymorphism.

Gene polymorphism of DNA repair gene X-ray repair cross complementing group 1 and xeroderma pigmentosum group D and environment interaction in non-small-cell lung cancer for Chinese nonsmoking female patients.

An association between genetic polymorphisms in encoding X-ray repair cross complementing group 1 (XRCC1) and encoding xeroderma pigmentosum group D (XPD) and risks of non-small-cell lung cancer (NSCLC) in East Chinese Han population has been observed. Herein we hypothesized that genetic polymorphisms in these two DNA repair genes are likely to be important in the NSCLC in Chinese nonsmoking female patients. We recruited 327 nonsmoking female patients with NSCLC and 342 individuals with benign lung diseases or healthy controls. Genotype frequencies of XRCC1 T-77C, Arg194Trp, Arg280His and Arg399Gln, Pro206Pro, and XPD Asp312Asn and Lys751Gln were calculated after Polymerase Chain Reaction amplification and sequencing. Generalized multifactor dimensionality reduction (GMDR) was used to detect the interactive effect of XRCC1 and XPD gene polymorphisms. The ratio of cooking oil mist exposure history and soot exposure history, and the gene frequencies of XRCC1 T-77C TC + CC, XRCC1 AG + GG, XRCC1 399Gln/Gln, and XPD 751Gln/Gln were higher in female patients with NSCLC than those with benign lung diseases or healthy controls. The haplotypes of XRCC1 T-Arg-Arg-Gln and XRCC1 C-Arg-Arg-Arg were positively associated with the NSCLC occurrence in nonsmoking female patients. GMDR discovered that there was an interactive model of XRCC1 and XPD genes in multiple gene loci. Logistic regression analysis showed that XRCC1 T-77C, XRCC1 Pro206Pro polymorphism, cooking oil mist and soot exposure history and tumor-node-metastasis (TNM) stage were related to NSCLC occurrence for nonsmoking female patients. Taken together, XRCC1 and XPD polymorphisms, cooking oil mist, and soot exposure history may be interactively correlated with NSCLC incidence for nonsmoking female patients.

Associations Between XPD Lys751Gln Polymorphism and Leukemia: A Meta-Analysis.

Objectives: The aim of the present study was to define the potential relationship between xeroderma pigmentosum group D (XPD) Lys751Gln polymorphisms and the risk of leukemia.Methods: A comprehensive search of Pubmed, Web of Science, EBSCO, the Cochrane Library and China National Knowledge Infrastructure was conducted to identify original articles published before March 2017 concerning the association between XPD Lys751Gln polymorphisms and leukemia risk. A literature quality assessment was performed using the Newcastle-Ottawa Scale. Heterogeneity across studies was assessed using I2 statistics. Random- or fixed-effects models were used to calculate pooled odds ratios (ORs) in the presence or absence of heterogeneity, respectively. Sensitivity analysis was used to assess the influence of individual studies on the pooled estimate. Publication bias was investigated using funnel plots and Egger’s regression test. All data analyses were performed using Stata 14.0 and Revman 5.3.Results: Fourteen studies with a total of 7525 participants (2,757 patients; 4,768 controls) were included in this meta-analysis. We found that XPD Lys751Gln polymorphisms significantly increased the risk of developing leukemia in both dominant OR = 1.21, 95%CI [1.10–1.35], P ≤ 0.001) and heterozygote (OR = 1.22, 95%CI [1.09–1.36], P ≤ 0.001) model. An allele model showed a borderline significant increase in leukemia risk (OR = 1.13, 95%CI [1.00–1.27], P = 0.05). A subgroup analysis revealed a consistent association between XPD Lys751Gln polymorphisms and leukemia risk for some genetic models in Caucasian populations, adult or chronic groups, and in almost all models of childhood or acute groups.Conclusion: Our results indicate that XPD Lys751Gln polymorphism increases the risk of leukemia, especially in childhood and acute cases.

Contribution of DNA repair xeroderma pigmentosum group D genotypes to pancreatic cancer risk in the Chinese Han population.

This study aimed to determine the association between the polymorphisms and haplotypes in the xeroderma pigmentosum group D (XPD) gene and the risk of pancreatic cancer in the Chinese Han population. SNaPshot was used for genotyping six SNP sites of the XPD gene. Comparisons of the correlations between different genotypes in combination with smoking and the susceptibility to pancreatic cancer were performed. Individual pancreatic cancer risk in patients who carry mutant C alleles (AC, CC, and AC+CC) at rs13181 increased (p < 0.05). Taking non-smoking individuals who carry the AA genotype as a reference, and non-smoking individuals who carry mutant allele C (AC+CC), the risk of pancreatic cancer increased by 3.343 times in individuals who smoked ≥ 20 cigarettes daily, 3.309 times in individuals who smoked ≥ 14 packs per year, 5.011 times in individuals who smoked ≥ 24 packs per year, and 4.013 times in the individuals who smoked ≥ 37 packs per year (P < 0.05). In addition, haplotype analysis revealed that haplotype AGG, which comprised rs13181, rs3916874 and rs238415, was associated with a 1.401-fold increase in pancreatic cancer risk (p < 0.05). We conclude that the polymorphism of XPD Lys751Gln (rs13181) in combination with smoking contributes to increased risk of pancreatic cancer in the Chinese Han population. Haplotype AGG might be a susceptibility haplotype for pancreatic cancer.

The XPD Lys751Gln polymorphism has predictive value in colorectal cancer patients receiving oxaliplatin-based chemotherapy: a systemic review and meta-analysis.

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. 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). 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). The XPD Lys751Gln polymorphism may have prognostic value in patients with CRC undergoing oxaliplatin-based chemotherapy.

Association Between XPD Lys751Gln and Asp312Asn Polymorphisms and Hepatocellular Carcinoma Risk

Genetic polymorphisms of xeroderma pigmentosum group D (XPD) in the nucleotide excision repair pathway may influence cancer susceptibility by affecting the capacity for DNA repair. Studies investigating the association between XPD Lys751Gln and Asp312Asn polymorphisms and hepatocellular carcinoma (HCC) risk reported inconsistent results. The aim of this study was to quantitatively summarize the evidence for such an association.Eligible studies were identified by searching electronic databases including PubMed, Embase, Cochrane library, and CBM, Chinese Biomedical Literature Database, for the period up to October 2014. The association of XPD Lys751Gln and Asp312Asn polymorphisms and HCC risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs).Finally, a total of 11 studies with 4322 cases and 4970 controls were included for XPD Lys751Gln polymorphism and 6 studies with 2223 cases and 2441 controls were available for XPD Asp312Asn polymorphism. With respect to XPD Lys751Gln polymorphism, statistically significant increased HCC risk was found when all studies were pooled into the meta-analysis (Gln/Gln vs Lys/Lys: OR = 1.363, 95% CI 1.065–1.744, P = 0.014; Lys/Gln vs Lys/Lys: OR = 1.205, 95% CI 1.099–1.321, P = 0.000; Gln/Gln+Lys/Gln vs Lys/Lys: OR = 1.300, 95% CI 1.141–1.480, P = 0.000). In subgroup analyses by ethnicity, source of control, Hardy–Weinberg equilibrium (HWE) in controls, hepatitis B virus (HBV) infection, and statistically significant increase of HCC risk was found in East Asians, population-based studies, studies consistent with HWE, and HBV-positive subjects, but not in mixed/other populations, hospital-based studies, studies deviating from HWE, and HBV-negative subjects. With respect to XPD Asp312Asn polymorphism, no significant association with HCC risk was found in the overall and subgroup analyses.The results suggest that the XPD Lys751Gln polymorphism contributes to increased HCC susceptibility, especially in East Asian populations. Further, large and well-designed studies are required to validate this association.

Association between the XPD/ERCC2 Lys751Gln polymorphism and risk of cancer: evidence from 224 case–control studies

Genetic variations in the xeroderma pigmentosum group D (XPD) gene may increase cancer susceptibility by affecting the capacity for DNA repair. A lot of studies have reported the association of XPD Lys751Gln polymorphism with risk of cancer, but the results remained controversial. Hence, we performed a systematic review and conducted a meta-analysis to explore association of the XPD Lys751Gln polymorphism with risk of cancer (78,398 cases and 103,178 controls from 224 studies). Overall, a significantly increased cancer risk was found in all genetic models (dominant model: odds ratio (OR) = 1.10, 95% confidence interval (CI) = 1.06-1.14; recessive model: OR = 1.10, 95% CI = 1.05-1.15; homozygous model: OR = 1.14, 95% CI = 1.08-1.21; heterozygous model: OR = 1.09, 95% CI = 1.05-1.12; additive model: OR = 1.08, 95% CI= 1.05-1.11) when all eligible studies were pooled into the meta-analysis. In further stratified and sensitivity analyses, the elevated risk of cancer remained for subgroups of breast cancer, esophageal cancer, hepatocellular cancer, leukemia, lung cancer, and melanoma. In summary, this meta-analysis suggests the XPD Lys751Gln polymorphism is a genetic susceptibility for some cancer types. Moreover, ethnicity, histological type of cancer, and smokers seem to contribute to varying expressions of the Lys751Gln on some cancer risk. In addition, our work also points out the importance of new studies for Lys751Gln association in endometrial cancer and ovarian cancer, where at least some of the covariates responsible for heterogeneity could be controlled, to obtain a more conclusive understanding about the function of the Lys751Gln polymorphism in cancer development.

MnSOD rs4880 and XPD rs13181 polymorphisms predict the survival of breast cancer patients treated with adjuvant tamoxifen

The enzyme manganese superoxide dismutase (MnSOD) defends against oxidative stress caused by reactive oxygen species (ROS), whereas Xeroderma pigmentosum group D (XPD) protein is involved in DNA repair. Polymorphisms in these genes have previously been associated with the outcome of breast cancer.Material and methods. Two gene polymorphisms, the MnSOD Val16Ala (rs4880A> G) and the XPD Lys751Gln (rs13181A> C), were analyzed in a cohort of 396 Finnish breast cancer patients by using PCR-RFLP-based methods in a prospective case-control study. The overall survival (OS), breast cancer-specific survival (BCSS), and relapse-free survival (RFS), assessed by using Kaplan-Meier survival analysis and multivariate Cox regression analysis, were evaluated according to the adjuvant treatments and the rs4880 and rs13181 genotypes.Results. In the combined analysis of rs4880 and rs13181 genotypes for patients treated with adjuvant tamoxifen (TAM) an increasing number of low-risk genotypes (rs4880 AA, rs4880 AG, or rs13181 AA) was significantly associated with better RFS, BCSS, and OS (n = 64). In addition, there was improved BCSS and RFS among TAM-treated patients carrying the wild-type rs4880 A allele as compared with the other genotypes (n = 64). The wild-type rs13181 AA genotype was similarly associated with better RFS and BCSS in the TAM-treated population (n = 65).Conclusion. This is the first study to show that the MnSOD rs4880 and XPD rs13181 polymorphisms may influence the outcome of breast cancer patients receiving adjuvant TAM monotherapy. Patients carrying the rs4880 A allele or rs13181 AA genotype may have a reduced ability to scavenge ROS and repair the DNA damage generated by TAM treatment.

No association between XRCC3 Thr241Met and XPD Lys751Gln polymorphisms and the risk of colorectal cancer in West Algerian population: a case–control study

Colorectal cancer (CRC) is a complex and multifactorial disease, in which genetic and environmental factors both seem to play a part. Many epidemiological studies have explored the association between genetic polymorphisms of X-ray repair cross-complementing group 3 (XRCC3) (Thr241Met) and Xeroderma pigmentosum group D (XPD) lysine to glutamine at codon 751 (Lys751Gln) and risk of CRC in various populations; however, the results are controversial. We conducted this case-control study in a West Algerian population to assess the potential role of this genetic polymorphism on the risk of CRC in this population. Genomic DNA was extracted from blood samples collected from 129 sporadic CRC patients and 148 normal controls. The polymorphisms were determined by pyrosequencing technique. The distribution of XRCC3 Thr241Met and XPD Lys751Gln genotypes among controls did not differ significantly from those predicted by the Hardy-Weinberg distribution (p > 0.05). There were no significant differences in the genotypes distribution and allele frequencies between CRC patients and controls. A significant association was found between the combined heterozygous of XRCC3 and homozygous variant of XPD gene and CRC. This is the first study on DNA repair genetic polymorphisms in West Algerian population, and it suggests that the XRCC3 Thr241Met and XPD Lys751Gln polymorphisms may not be associated with the CRC risk in this population.

XPD Lys751Gln polymorphism is not associated with oral cancer risk: evidence from a meta-analysis

Several studies have investigated the association between xeroderma pigmentosum group D (XPD) Lys751Gln polymorphism and oral cancer. However, the impact of XPD Lys751Gln polymorphism on oral cancer risk is unclear, owing to the obvious inconsistence among those studies. The aim of this study was to derive a more precise estimation of the association of XPD Lys751Gln polymorphism with oral cancer by performing a meta-analysis. Data were analyzed using Stata, and publication bias was estimated. We included seven study populations, comprising 1,093 cases and 2,637controls from seven publications. The pooled odds ratio (OR) with their 95 % confidence interval (95 % CI) was calculated to assess the association between XPD Lys751Gln polymorphism and risk of oral cancer. Overall, there was no association between XPD Lys751Gln polymorphism and oral cancer risk under all genetic models (Gln/Gln versus Lys/Lys: OR = 1.23, 95 % CI 0.78-1.96, p = 0.04; Lys/Gln + Gln/Gln versus Lys/Lys: OR = 1.13, 95 % CI 0.87-1.48, p = 0.03; Gln/Gln versus Lys/Gln + Lys/Lys: OR = 1.14, 95 % CI 0.79-1.63, p = 0.16; Lys/Gln versus Lys/Lys: OR = 1.12, 95 % CI 0.89-1.40, p = 0.131). Subgroup analysis by ethnicity suggested that there was no association between XPD Lys751Gln polymorphism and oral cancer risk in both Asians and Caucasians. These results suggest that XPD Lys751Gln polymorphism is not related to oral cancer risk. Further large and well-designed studies are required to confirm this conclusion.

Polymorphisms in DNA repair genes (APEX1, XPD, XRCC1 and XRCC3) and risk of preeclampsia in a Mexican mestizo population.

Variations in genes involved in DNA repair systems have been proposed as risk factors for the development of preeclampsia (PE). We conducted a case-control study to investigate the association of Human apurinic/apyrimidinic (AP) endonuclease (APEX1) Asp148Glu (rs1130409), Xeroderma Pigmentosum group D (XPD) Lys751Gln (rs13181), X-ray repair cross-complementing group 1 (XRCC) Arg399Gln (rs25487) and X-ray repair cross-complementing group 3 (XRCC3) Thr241Met (rs861539) polymorphisms with PE in a Mexican population. Samples of 202 cases and 350 controls were genotyped using RTPCR. Association analyses based on a χ2 test and binary logistic regression were performed to determine the odds ratio (OR) and a 95% confidence interval (95% CI) for each polymorphism. The allelic frequencies of APEX1 Asp148Glu polymorphism showed statistical significant differences between preeclamptic and normal women (p = 0.036). Although neither of the polymorphisms proved to be a risk factor for the disease, the APEX1 Asp148Glu polymorphism showed a tendency of association (OR: 1.74, 95% CI = 0.96–3.14) and a significant trend (p for trend = 0.048). A subgroup analyses revealed differences in the allelic frequencies of APEX1 Asp148Glu polymorphism between women with mild preeclampsia and severe preeclampsia (p = 0.035). In conclusion, our results reveal no association between XPD Lys751Gln, XRCC Arg399Gln and XRCC3 Thr241Met polymorphisms and the risk of PE in a Mexican mestizo population; however, the results in the APEX1 Asp148Glu polymorphism suggest the need for future studies using a larger sample size.

Association between XPD Lys751Gln polymorphism and bladder cancer susceptibility: an updated and cumulative meta-analysis based on 6,836 cases and 8,251 controls

The association between xeroderma pigmentosum group D (XPD) Lys751Gln polymorphism and bladder cancer (BC) susceptibility was investigated by two meta-analyses, however, their results were contrary. We conjecture the reason might be the sample size, thus we performed this updated and cumulative meta-analysis using the Comprehensive Meta-Analysis software. We searched PubMed up to August 25th, 2013 and yielded 20 published articles with 21 case-control trails including 6,836 BC patients and 8,251 controls. The meta-analysis results showed that XPD Lys751Gln polymorphism was borderline significantly associated with BC susceptibility for overall population [Gln vs. Lys: OR 1.07, 95% CI 1.01-1.12, P = 0.01; Gln/Gln vs. Lys/Lys: OR 1.15, 95% CI 1.03-1.29, P = 0.01; Gln/Gln vs. (Lys/Gln + Lys/Lys): OR 1.13, 95% CI 1.02-1.26, P = 0.02]. The cumulative meta-analysis according to the publication year showed the CI became increasingly narrower and tended to have statistical significance for the studies incessantly accumulated. In the subgroup analysis according to ethnicity, there was a significant association in Asian population and no association in Caucasian population. There was no publication bias detected. However, due to the limitations and cumulative analysis result of this meta-analysis, more well-designed and larger studies with risk factors adjusted are suggested to be performed to obtain a conclusive result on this topic.

Association of XPD Lys751Gln polymorphism with head and neck cancer susceptibility: evidence from 11,443 subjects

BackgroundWhether the single nucleotide polymorphism (SNP) Lys751Gln of xeroderma pigmentosum group D(XPD) gene increases susceptibility to head and neck cancer (HNC) is controversial and undetermined. Therefore, we conducted this meta-analysis to systematically assess the possible association between them.MethodsThe OVID, Medline, Embase, Pubmed, Web of Science databases were searched to identify the eligible studies. The odds ratio (OR) with 95% confidence interval (95% CI) were used to assess the strength of association.ResultsA total of 11,443 subjects from eighteen studies were subjected to meta-analysis. Overall, XPD Lys751Gln polymorphism had no association with increased HNC risk under all five genetic models (P > 0.05). In the subgroup analysis by ethnicity and source of controls, still no significant association was found under five genetic models (P > 0.05). In the subgroup analysis by cancer type, XPD Lys751Gln polymorphism had statistically significant association with elevated laryngeal cancer (LC) and nasopharyngeal cancer (NPC) risk under heterozygous comparison and dominant model (P<0.05) and borderline significantly increased risk was found under allele contrast for LC and NPC. Carriers of Lys allele and Lys/Lys genotype may be associated with elevated LC and NPC risk.ConclusionsThere is overall lack of association between XPD Lys751Gln polymorphism and HNC risk under all five genetic models and still no significant association was found in the subgroup analysis by ethnicity and source of controls. However, XPD Lys751Gln polymorphism was significantly associated with susceptibility to LC and NPC and the Lys allele and Lys/Lys genotype of XPD Lys751Gln polymorphism may be a risk factor for LC and NPC. However, relatively modest sample sizes were included in this meta-analysis and studies with large sample sizes and representative population are warranted to further clarify this finding.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5628716106316015.

Xeroderma pigmentosum group D polymorphisms and esophageal cancer susceptibility: a meta-analysis based on case-control studies.

To clarify the effects of the xeroderma pigmentosum group D (XPD) Asp312Asn and Lys751Gln gene polymorphisms on the risk of esophageal cancer (EC). A computerised literature search was conducted to identify the relevant studies from the PUBMED and EMBASE databases, reviews, and reference lists of relevant articles. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the associations between the XPD Asp312Asn and/or Lys751Gln polymorphisms and EC susceptibility. Statistical analyses were performed using the software Stata 12.0. A fixed or random effects model was selected based on a heterogeneity test. Publication bias was estimated using funnel plots and Egger's linear regression method. Subgroup analyses were performed based on histological type and ethnicity. Thirteen case-control studies with a total of 10 comparisons for the Asp312Asn polymorphism, including 2373 cases and 3175 controls, and 15 comparisons for the Lys751Gln polymorphism, including 3226 cases and 5237 controls, were recruited for the meta-analysis. In terms of the XPD Asp312Asn polymorphism, significantly increased EC risks were identified in the Asp/Asn vs Asp/Asp comparison (OR = 1.17, 95%CI: 1.02-1.33, P = 0.03) and in the dominant-model comparison (Asn/Asn+Asp/Asn vs Asp/Asp: OR = 1.18, 95%CI: 1.04-1.34, P = 0.01). However, no significant associations were found in the Asn/Asn vs Asp/Asp comparison (OR = 1.30, 95%CI: 1.00-1.70, P = 0.05) or in the recessive-model comparison (Asn/Asn vs Asp/Asn + Asp/Asp: OR = 1.17, 95%CI: 0.91-1.50, P = 0.22). In terms of the XPD Lys751Gln polymorphism, a significant association with EC susceptibility was found under the recessive model (Gln/Gln vs Lys/Gln+Lys/Lys: OR = 1.21, 95%CI: 1.02-1.43, P = 0.03). However, no associations were identified in the other comparisons (co-dominant model: Lys/Gln vs Lys/Lys: OR = 1.11, 95%CI: 0.94-1.31, P = 0.20; Gln/Gln vs Lys/Lys: OR = 1.31, 95%CI: 0.98-1.75, P = 0.07; dominant model: OR = 1.14, 95%CI: 0.96-1.35, P = 0.14). The results of this meta-analysis suggest that the XPD Asp312Asn and Lys751Gln gene polymorphisms are associated with a significantly increased risk for EC.

Association of xeroderma pigmentosum group D (Asp312Asn, Lys751Gln) and cytidine deaminase (Lys27Gln, Ala70Thr) polymorphisms with outcome in Chinese non-small cell lung cancer patients treated with cisplatin-gemcitabine.

Xeroderma pigmentosum group D (XPD) plays a key role in the repair of DNA and platinum resistance lesions. Cytidine deaminase (CDA) genes determine the velocity of gemcitabine catalysis. This study aimed to investigate the relationship between XPD and CDA genotypes and outcome in non-small lung cancer (NSCLC) patients. We used polymerase chain reaction-restriction fragment length polymorphism to evaluate genetic polymorphisms of XPD (Asp312Asn and Lys751Gln) and CDA (Lys27Gln and Ala70Thr) in 93 NSCLC patients treated with a cisplatin-gemcitabine regimen. There were no significant correlations between the XPD polymorphisms Asp312Asn and Lys751Gln with clinical benefits (P>0.05). Time to progression (TTP) did not differ between patients with wild type genotypes and those heterozygous for the single nucleotide polymorphism loci of XPD. However, a significant difference was observed in overall survival (OS) between XPD Asp312Asp and XPD Asp312Asn individuals (20.0 vs 12.4 months, P=0.04). Furthermore, the OS of patients with wild type genotypes was longer (20.5 months) than that of patients carrying the XPD 751Lys/Gln polymorphism (11.5 months). No significant differences in TTP or OS were observed in patients carrying different genotypes of CDA Lys27Gln, and no mutations were observed at the CDA Ala70Thr site. These results provide suggestive evidence of a favorable effect for the XPD 312Asp/Asp and XPD 751Lys/Lys genotypes with respect to overall survival rates in platinum-treated NSCLC patients. However, the CDA 27 polymorphism does not appear to affect the efficacy of gemcitabine.

Polymorphisms in XPD Gene Could Predict Clinical Outcome of Platinum-Based Chemotherapy for Non-Small Cell Lung Cancer Patients: A Meta-Analysis of 24 Studies

Objective Xeroderma pigmentosum group D (XPD) is an essential gene involved in the nucleotide excision repair (NER) pathway. Two commonly studied single nucleotide polymorphisms (SNPs) of XPD (Lys751Gln, A>C, rs13181; Asp312Asn, G>A, rs1799793) are implicated in the modulation of DNA repair capacity, thus related to the responses to platinum-based chemotherapy. Here we performed a meta-analysis to better evaluate the association between the two XPD SNPs and clinical outcome of platinum-based chemotherapy in non-small cell lung cancer (NSCLC) patients.MethodsA comprehensive search of PubMed database was conducted to identify relevant articles. Primary outcomes included objective response (i.e., complete response + partial response vs. stable disease + progressive disease), progression-free survival (PFS) and overall survival (OS). The pooled and 95% confidence intervals (CIs) of ORs (odds ratios) and HRs (hazard ratios) were estimated using the fixed or random effect model.ResultsTwenty-four studies were eligible according to the inclusion criteria. None of the XPD Lys751Gln/Asp312Asn polymorphisms was associated with objective response, PFS or OS in NSCLC patients treated with platinum drugs. However, in stratified analysis by ethnicity, the XPD Lys751Gln (A>C) polymorphism was not significantly associated with increased response in Caucasians (OR = 1.35, 95%CI = 1.0–1.83, P = 0.122 for heterogeneity) but was associated with decreased PFS in Asians (HR = 1.39, 95%CI = 1.07–1.81, P = 0.879 for heterogeneity). Furthermore, a statistically significant difference existed in the estimates of effect between the two ethnicities (P = 0.014 for TR; P<0.001 for PFS).Conclusions XPD Lys751Gln (A>C) may have inverse predictive and prognostic role in platinum-based treatment of NSCLC according to different ethnicities. Further studies are needed to validate our findings.

Predictive Effect of XPA and XPD Polymorphisms on Survival of Advanced NSCLC Patients Treated with Platinum-Based Chemotherapy: A Three-Dimensional (3-D), Polyacrylamide Gel-Based DNA Microarray Method

Platinum-based chemotherapy is a primary treatment for patients with advanced non-small cell lung cancer (NSCLC). Considering individual differences, an effective and convenient method is urgently needed to identify the sensitivity of individual patient to platinum based regimen. Genetic variants in DNA repair genes are presumed to represent important determinants of drug efficacy. Our previous studies have demonstrated the involvement of xeroderma pigmentosum group A (XPA) codon23 and xeroderma pigmentosum group D (XPD) codon751 single-nucleotide polymorphisms (SNPs) in clinical response to platinum based chemotherapy in advanced NSCLC patients. Thus, a follow-up study was carried out to investigate the relevance of these genotypes and survival of the cohort (n = 115). The three-dimensional (3-D), polyacrylamide gel-based DNA microarray method was used to assess the genotypes of XPA and XPD in peripheral lymphocytes. Log-rank test revealed that the variant genotypes of XPA23 (A/G+G/G) were associated with significantly longer progression- free survival (PFS) (6.0 m vs. 10.6 m, log-rank P = 0.001) and overall survival (OS) (11.2 m vs. 20.8 m, log-rank P = 0.001). In Cox proportional hazards model, the hazard ratio (HR) for death in patients with G allele was 0.65 (P = 0.049). While no significant differences were observed in PFS or OS according to XPD Lys751Gln genotypes (log-rank P > 0.05). In combination with our previous short-term clinical results, this study further confirmed that by detecting the SNPs in blood cells, XPA A23G polymorphic variants might be a promising biomarker in predicting a favor prognosis of NSCLC patients and be helpful towards designing individualized treatments.

Genetic polymorphisms of xeroderma pigmentosum group D gene Asp312Asn and Lys751Gln and susceptibility to prostate cancer: A systematic review and meta-analysis

Many studies have reported the role of xeroderma pigmentosum group D (XPD) with prostate cancer risk, but the results remained controversial. To derive a more precise estimation of the relationship, a meta-analysis was performed. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association between XPD Asp312Asn and Lys751Gln polymorphisms and prostate cancer risk. A total of 8 studies including 2620 cases and 3225 controls described Asp312Asn genotypes, among which 10 articles involving 3230 cases and 3582 controls described Lys751Gln genotypes and were also involved in this meta-analysis. When all the eligible studies were pooled into this meta-analysis, a significant association between prostate cancer risk and XPD Asp312Asn polymorphism was found. For Asp312Asn polymorphism, in the stratified analysis by ethnicity and source of controls, prostate cancer risk was observed in co-dominant, dominant and recessive models, while no evidence of any associations of XPD Lys751Gln polymorphism with prostate cancer was found in the overall or subgroup analyses. Our meta-analysis supports that the XPD Asp312Asn polymorphism contributed to the risk of prostate cancer from currently available evidence. However, a study with a larger sample size is needed to further evaluate gene–environment interaction on XPD Asp312Asn and Lys751Gln polymorphisms and prostate cancer risk.

Predictive Value of XPD Polymorphisms on Platinum-Based Chemotherapy in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis

BackgroundThe correlation between xeroderma pigmentosum group D (XPD) polymorphisms (Lys751Gln and Asp312Asn) and clinical outcomes of non-small cell lung cancer (NSCLC) patients, who received platinum-based chemotherapy (Pt-chemotherapy), is still inconclusive. This meta-analysis was aimed to systematically review published evidence and ascertain the exact role of XPD polymorphisms.MethodsDatabases of MEDLINE and EMBASE were searched up to April 2013 to identify eligible studies. A rigorous quality assessment of eligible studies was conducted according the Newcastle-Ottawa Quality Assessment Scales. The relationship between XPD polymorphisms and response to Pt-chemotherapy and survival was analyzed.ResultsA total of 22 eligible studies were included and analyzed in this meta-analysis. The overall analysis suggested that the XPD Lys751Gln polymorphism was not associated with response to Pt-chemotherapy or survival. However, the XPD 312Asn allele was significantly associated with poor response to Pt-chemotherapy compared with the Asp312 allele (Asn vs. Asp: OR = 0.435, 95% CI: 0.261–0.726). Additionally, the variant genotype of XPD Asp312Asn polymorphism was associated with favorable survival in Caucasian (AspAsn vs. AspAsp: HR = 0.781, 95% CI: 0.619–0.986) but unfavorable survival in Asian (AspAsn+AsnAsn vs. AspAsp: HR = 1.550, 95% CI: 1.038–2.315).ConclusionsThese results suggest that XPD Asp312Asn polymorphism may function as a predictive biomarker on platinum-based chemotherapy in NSCLC and further studies are warranted.