Xeroderma pigmentosum group D (XPD) gene is the second subunit of basic transcript factor TFII H; it plays an important role in transcription and nucleotide excision repair. In this study, using the total RNA extracted from HeLa cells, we cloned the human full length XPD by RT-PCR and inserted it into the pEGFP-N2 plasmid vector which expressed the green fluorescence protein (GFP). Then the recombinant plasmid pEGFP-N2/XPD was transfected into the human hepatoma carcinoma cell Hep3B integrated with HBx protein,and we analysed the expression of HBx and the proliferative ability of recombinant cells. The data collected from this study could serve as a physical basis on which to further investigate the biological activities of XPD.
Cloning, Molecular ; DNA Repair ; Female ; HeLa Cells ; Humans ; Liver Neoplasms ; genetics ; Recombinant Proteins ; genetics ; metabolism ; Trans-Activators ; genetics ; Transcription Factor TFIIH ; genetics ; Transcription, Genetic ; Transfection ; Viral Regulatory and Accessory Proteins ; genetics ; Xeroderma Pigmentosum Group D Protein ; genetics ; metabolism

BACKGROUND AND OBJECTIVEIt has been proven that close relation was existed between XPD polymorphism G312A and lung cancer risk. However, some of the results are not consistent. The aim of this study is to explore the impact of DNA repair gene XPD polymorphism G312A on lung cancer risk.

METHODSThe literatures eligible from PUBMED, EMBASE, CNKI and WANGFANG database were enrolled in the meta-analysis. Heterogeneity among combined studies was assessed. The pooled OR and 95%CI were calculated. The sensitivity analysis and the publication bias were evaluated by RevMan 5.0 and STATA 11.0.

RESULTSThere were 6554 cases and 8322 controls from 18 studies included in the meta-analysis. In total, individuals with 312A allele and 312AA genotype showed increased lung cancer risk (A vs. G: OR = 1.06, 95% CI: 1.00-1.12; AA vs. AG+GG: OR = 1.20, 95% CI: 1.06-1.36; AA vs. GG: OR = 1.19, 95% CI: 1.04-1.36). In Asians, individuals with 312AA genotype showed 6.15 fold and 6.20 fold increased lung cancer risk in recessive genetic model and homogenous contrast respectively (AA vs. AG+GG: OR = 7.15, 95% CI: 1.90-26.94; AA vs. GG: OR = 7.20, 95% CI: 1.91-27.15). In Caucasians, individuals with 312AA genotype showed a 15% increased lung cancer risk (OR = 1.15, 95% CI: 1.01-1.31).

CONCLUSIONXPD 312A allele is risk allele for lung cancer. Individuals with AA genotype have higher risk of lung cancer, especially in Asians.

Genotype ; Humans ; Lung Neoplasms ; etiology ; genetics ; Odds Ratio ; Polymorphism, Genetic ; Xeroderma Pigmentosum Group D Protein ; genetics

OBJECTIVETo study the association between polymorphism of DNA repair gene xeroderma pigmentosum G (XPG) Asp1104His and the risks of developing laryngeal and hypopharyngeal carcinomas.

METHODSTotally 175 patients with laryngeal or hypopharyngeal carcinoma and 525 cancer-free controls were genotyped for the polymorphism by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The odds ratio (OR) and 95% confidence interval (CI) were calculated using unconditional logistic regression model.

RESULTSCompared with those having the Asp/Asp genotype, patients having the XPG 1104Asp/His genotype had a higher risk for laryngeal carcinoma (OR = 2.46, 95% CI = 1.15-5.24, P < 0.05), but not for hypopharyngeal carcinoma (OR = 1.36, 95% CI = 0.87-2.12, P > 0.05). In addition, the XPG 1104Asp/His genotype appeared to be associated with well differentiated squamous cell carcinoma in both larynx and hypopharynx (OR = 1.88, 95% CI = 1.05-3.40, P < 0.05 ).

CONCLUSIONThe XPG Asp1104His polymorphism may play a role in the development of laryngeal and hypopharyngeal carcinomas.

Case-Control Studies ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Hypopharyngeal Neoplasms ; genetics ; pathology ; Laryngeal Neoplasms ; genetics ; pathology ; Male ; Polymorphism, Genetic ; Xeroderma Pigmentosum Group D Protein ; genetics

This study was aimed to explore the relationship between the single nucleotide polymorphisms of XPD (G23591A, A35931C) and individual susceptibility to non-Hodgkin's lymphomas (NHL) in Shandong populations. XPD gene polymorphism in 309 cases of NHL and 305 healthy controls were detected using PCR-restriction fragment length polymorphism assay in a case-control molecular epidemiology study. The association between gene polymorphism and the risk of NHL were examined through comparing odds ratio (OR) and 95% confidence interval (CI) between two groups. The results showed that no significant association between the XPD (G23591A, A35931C) polymorphism and the risk of whole NHL was shown at first. In the further analysis, all NHL cases were divided into four groups: follicular lymphoma (FL) group, diffuse large B-cell lymphoma (DLBCL) group, T-cell lymphoma group and other B-cell lymphoma group. Frequencies of XPD 23591GA + AA genotypes were 16.3%, 18.0%, 10.5% and 18.4% in each subgroup respectively, while 12.5% in control. Individuals carrying GA + AA genotype had 1.43, 1.58, 0.89 and 1.50-fold risk of NHL sub groups as much as GG genotype, but no statistically significant difference between subgroups and control was found (p>0.05); frequencies of XPD 35931AC + CC genotypes were 15.2%, 15.8%, 18.4% and 12.5% in each subgroup, while 11.5% in control. Individuals carrying AC + CC genotype had 1.41, 1.48, 1.75 and 1.12-fold risk of NHL subgroup as much as AA genotype, but there were also no statistically significant difference between each subgroup and control (p>0.05). It is concluded that the gene polymorphism of XPD (G23591A, G935931C) does not associate with the risk of developing NHL in Shandong populations.
Adult ; DNA Repair ; Female ; Humans ; Lymphoma, Non-Hodgkin ; genetics ; Male ; Middle Aged ; Point Mutation ; Polymorphism, Genetic ; Risk Factors ; Xeroderma Pigmentosum Group D Protein ; genetics ; Young Adult

OBJECTIVETo explore the association between polymorphisms in the DNA repair gene, xeroderma pigmentosum group D (XPD), and development of hepatocellular carcinoma (HCC) in the Chinese population by performing a systematic review of the previously published clinical data.

METHODA comprehensive literature search of the BIOSIS Previews and PubMed databases was carried out to identify all case-control studies of XPD polymorphisms and HCC risk. Meta-analysis was conducted to calculate the pooled odds ratios (ORs) with 95% confidence intervals (CIs) of developing HCC for carriers of the various XPD polymorphisms.

RESULTSSix case-control studies were selected for this meta-analysis, and comprised a total of 3424 HCC cases and 3636 controls. The pooled ORs (95% CIs) of XPD codon 751 and 312 allelomorphs were 1.25 (0.70 to 2.24) and 0.85 (0.58 to 1.25), respectively. Compared with the XPD wild-type homozygote Lys/Lys genotype of codon 751, the pooled OR (95% CI) of Lys/G1n + Gln/Gln genotypes for HCC risk was 1.31 (0.71 to 2.42). Compared with the XPD wild-type homozygote Asp/Asp genotype of codon 312, the pooled OR (95% CI) of Asp/Asn + Asn/Asn genotypes for HCC risk was 1.19 (0.73 to 1.95).

CONCLUSIONPolymorphisms in the XPD codons 751 and 312 are not associated with HCC risk in the Chinese population.

Carcinoma, Hepatocellular ; genetics ; Codon ; genetics ; DNA Repair ; Genetic Predisposition to Disease ; Humans ; Liver Neoplasms ; genetics ; Polymorphism, Genetic ; Xeroderma Pigmentosum Group D Protein ; genetics

OBJECTIVETo explore the influence of the DNA repair gene ERCC2 single nucleotide polymorphisms (SNPs) rs13181, rs1618536, and rs1799793 on male idiopathic infertility in Ningxia, China.

METHODSUsing MassArray, we conducted a case-control study and genotyped three ERCC2 SNPs rs13181, rs1618536, and rs1799793 for 351 males (aged 31.0 +/- 4.2 years) with idiopathic infertility and another 327 normal fertile men (aged 33.0 +/- 5.9 years) as controls.

RESULTSThe ERCC2 AnyG-anyA-anyA genotypes were significantly associated with an increased risk of idiopathic infertility (OR 0.414, 95% CI 0.176 - 0.970), while the three single ERCC2 SNPs rs13181, rs1618536, and rs1799793 showed no significant differences between the cases and controls (P > 0.05).

CONCLUSIONThe ERCC2 SNPs rs13181, rs1618536, and rs1799793 play a role of interaction in male idiopathic infertility in Ningxia, contributing to the risk of the disease.

Adult ; Case-Control Studies ; China ; DNA Repair ; Genotype ; Humans ; Infertility, Male ; genetics ; Male ; Polymorphism, Single Nucleotide ; Xeroderma Pigmentosum Group D Protein ; genetics

BRCA1 Protein ; genetics ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Designer Drugs ; therapeutic use ; Humans ; Lung Neoplasms ; drug therapy ; Precision Medicine ; methods ; Tubulin ; genetics ; Xeroderma Pigmentosum Group D Protein ; genetics

OBJECTIVETo explore the relationship of polymorphisms in the xeroderma pigmentosum group D (XPD) gene and the glutathione-S transferees M1 (GSTM1) gene with susceptibility to primary hepatic carcinoma (PHC) in Tibetans from the Qinghai region.

METHODSThis case-control study compared equal groups (n=102 each) of patients with PHC and healthy individuals recruited from Qinghai, Tibet.PCR and denaturing high-performance liquid chromatography (DHPLC) was used to detect each participant's genotypes for the XPD and GSTM1 genes.Non-conditional logistic regression modeling was used in multivariate analysis to evaluate the predictive value for PHC, to compare the risk of different genotypes for PHC, and to assess the risk of gene polymorphisms and environmental factors for PHC.

RESULTSSix factors, including smoking, carnivorous diet, alcohol consumption, hepatitis B virus (HBV) infection, immediate family members with HBV infection and immediate family members with history of PHC, were included in the logistic regression model (alpha =0.05).The XPD751C mutation genotype distribution frequencies were significantly higher in the cases than in the controls (21.6% vs. 10.8%, P=0.036). The risk of PHC increased 2.275 times (95% CI, 1.04-4.98). The frequencies of the GSTM1 genotype were remarkably higher in the cases than in the controls (60.4% vs. 39.6%, P=0.017), suggesting this as an exposure factor. Individuals with the GSTM1 genotype had 1.963 times higher risk of PHC than individuals without the GSTM1 genotype (95% CI, 1.124-3.428). With both the XPD751C mutation and the GSTM1 genotype as exposure factors, the risk incidence increased to 3.030 times (95% CI, 1.165-7.881), indicating that the combined genotypes have a synergistic effect.Application of unconditioned logistic stepwise regression analysis of the genotypes and environmental risk factors showed an interaction between the XPD751C mutation and HBV infection, alcohol consumption and immediate family members with history of PHC. In addition, an interaction between the GSTM1 genotype and HBV infection was found.

CONCLUSIONAlcohol consumption, HBV infection and the presence of immediate family members with HBV infection are the main environmental risk factors of PHC in Qinghai Tibetans.Qinghai Tibetans who carry the XPD751C gene mutation and the GSTM 1 genotype are at increased risk of PHC, compared to individuals carrying only one or the other.The XPD751C mutation may increase risk of PHC when combined with the environmental factors.

Alcohol Drinking ; Carcinoma, Hepatocellular ; genetics ; Case-Control Studies ; Genetic Predisposition to Disease ; Genotype ; Glutathione ; Glutathione Transferase ; genetics ; Humans ; Incidence ; Liver Neoplasms ; genetics ; Logistic Models ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Risk Factors ; Smoking ; Tibet ; Xeroderma Pigmentosum Group D Protein ; genetics

OBJECTIVETo explore association genetic polymorphism of XPD with chromosomal damage in workers exposed to radiation.

METHODS182 workers exposed to radiation for at least one year with chromosomal damage were selected as cases based on a general health examination for all workers exposed to radiation in Tangshan city. The control group without chromosomal damage was matched to case by age (within 5 years), sex, work unit, type of exposed to radiation, cumulate serve length (within 1 year) according to 1:1. The micro whole blood cultivation was used for the chromosome analysis. The chromosome aberration type and rate were observed and counted. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to examine the genotype of three XPD loci (751, 312 and 156).

RESULTSThe frequency of XPD 751 AA in cases was higher than that in controls (P < 0.05). The frequency of 751 allele in case group was statistically higher than that in the control groups (P < 0.05). No statistical difference was found in the frequencies of XPD 312 genotype and allele between the case and control group (P > 0.05). 156 mutant gene type in case group was higher than that in the control groups. The frequency of 156 A allele in case group were higher than that of the control groups (P < 0.05). The frequency of genotype with both 751AA and 156CA or 751AA and 156AA was higher in cases than that of controls (P < 0.05).

CONCLUSIONXPD 751AA genotype is a possible risk factor for radiation-induced chromosomal damage. XPD 156 mutant gene type is a possible risk factor for radiation-induced chromosomal damage. Individuals with both XPD 751AA and 156 (CA+AA) genotypes are susceptible to radiation-induced chromosomal damage. No association of XPD 312 polymorphism with radiation-induced chromosomal damage is found.

Adult ; Case-Control Studies ; Chromosome Aberrations ; radiation effects ; Female ; Genetic Predisposition to Disease ; Humans ; Male ; Middle Aged ; Occupational Exposure ; adverse effects ; Polymorphism, Restriction Fragment Length ; Radiation ; Xeroderma Pigmentosum Group D Protein ; genetics ; Young Adult

OBJECTIVETo confirm the enhancing effect of excision repair cross complementing rodent repair deficiency gene 2 (ERCC2) on alkylating agents resistance.

METHODSThe authors constructed a pcDNA3-ERCC2 plasmid. The pcDNA3-ERCC2 was transfected into a selected ERCC2 negative human glioma cell line, SKMG-4, using liposome-mediated transfection. After G418 selection, a stable transfected cell line was obtained and tested for cytotoxicity of several alkylating agents.

RESULTSThe stable transfectant was obtained and confirmed by RT-PCR as well as Western blot analysis to be strongly expressing ERCC2 at both mRNA and protein levels. The IC(90) ( micro mol/L) of two alkylating agents, cisplatin and melphalan, increased from 1.0 to 1.75 (75%) and 5.6 to 9.0 (61%), respectively, compared with control cell line.

CONCLUSIONThe present data provided evidences and confirmed the authors' previous results that ERCC2 contributes, at least partially, to alkylating agent resistance in human glioma cell line.

Antineoplastic Agents, Alkylating ; pharmacology ; Cisplatin ; pharmacology ; DNA Helicases ; DNA-Binding Proteins ; Drug Resistance, Neoplasm ; genetics ; Glioma ; Humans ; Melphalan ; pharmacology ; Proteins ; genetics ; Transcription Factors ; Transfection ; Tumor Cells, Cultured ; Xeroderma Pigmentosum Group D Protein