Association of ERCC1 rs3212986 and ERCC2 rs13181 polymorphisms with the risk of glioma

Several previous studies have reported the role variant of ERCC1 rs3212986 and ERCC2 rs13181 polymorphisms in the risk of glioma, but the results of these studies are inconsistent. Therefore, we aimed to conduct a meta-analysis to investigate the role of ERCC1 rs3212986 and ERCC2 rs13181 on the risk of glioma. A comprehensive research was conducted through the databases of Pubmed, EMBASE and the China National Knowledge Infrastructure [CNKI] platforms until June 1, 2014, including 14 eligible case-control studies. Our meta-analysis found that ERCC1 rs3212986 AA genotype was significantly associated with increased risk of glioma compared with CC genotype, and the pooled OR [95%CI] was 1.29[1.07-1.55]. By subgroup analysis, ERCC1 rs3212986 AA genotype was found to be significantly correlated with increased glioma risk in Chinese population [OR=1.37, 95%CI=1.07, 1.55], Similarly, we found that ERCC2 rs13181 GT and TT genotypes were significantly associated with increased risk of glioma in Chinese population, with ORs [95%CI] of 1.47[1.17-1.85] and 1.50[1.02-2.22]. But ERCC1 rs3212986 and ERCC2 rs13181 polymorphisms had no significant association with glioma risk in Caucasian populations. By begg's funnel plot, we found that no publication bias was existed in this meta-analysis. Our meta-analysis suggested that ERCC1 rs3212986 and ERCC2 rs13181 polymorphism play an important risk factor for brain tumor development in Chinese population, but no association in Caucasian populations

Relationship between ERCC2 single nucleotide polymorphisms and male idiopathic infertility in Ningxia / 中华男科学杂志

<p><b>OBJECTIVE</b>To explore the influence of the DNA repair gene ERCC2 single nucleotide polymorphisms (SNPs) rs13181, rs1618536, and rs1799793 on male idiopathic infertility in Ningxia, China.</p><p><b>METHODS</b>Using 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.</p><p><b>RESULTS</b>The 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).</p><p><b>CONCLUSION</b>The ERCC2 SNPs rs13181, rs1618536, and rs1799793 play a role of interaction in male idiopathic infertility in Ningxia, contributing to the risk of the disease.</p>

Relation of polymorphisms of the XPD and GSTM1 genes with susceptibility to hepatocellular carcinoma in Qinghai Tibetans / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To 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.</p><p><b>METHODS</b>This 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.</p><p><b>RESULTS</b>Six 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.</p><p><b>CONCLUSION</b>Alcohol 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.</p>

DNA Repair Genes XRCC1, XRCC3, XPD, and OGG1 Polymorphisms among the Central Region Population of Saudi Arabia

DNA repair is one of the central defense mechanisms against mutagenic exposures. Inherited SNPs of DNA repair genes may contribute to variations in DNA repair capacity and susceptibility to cancer. Due to the presence of these variants, inter-individual and ethnic differences in DNA repair capacity have been established in various populations. Saudi Arabia harbors enormous genetic and cultural diversity. In the present study we aimed to determine the genotype and allele frequencies of XRCC1 Arg399Gln (rs25487), XRCC3 Thr241Met (rs861539), XPD Lys751Gln (rs13181), and OGG1 Ser326Cys (rs1052133) gene polymorphisms in 386 healthy individuals residing in the central region of Saudi Arabia and compare them with HapMap and other populations. The genotype and allele frequencies of the four DNA repair gene loci in central Saudi population showed a distinctive pattern. Furthermore, comparison of polymorphisms in these genes with other populations also showed a unique pattern for the central Saudi population. To the best of our knowledge, this is the first report that deals with these DNA repair gene polymorphisms among the central Saudi population.

The association between genetic polymorphisms of DNA repair genes XPD, XPC and susceptibility to laryngeal carcinoma / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To analyze the association between genetic polymorphisms of DNA repair genes of XPD (751 Lys/Gln), XPC (PAT)and susceptibility to laryngeal carcinoma. To explore the effect between DNA repair genes of XPD (751 Lys/Gln), XPC (PAT) and carcinogenesis of LSCC(laryngeal squamous cell carcinoma).@*METHOD@#A case-control study was conducted involving 233 LSCC patients and 102 healthy controls to investigate the association between polymorphisms of XPD(751 Lys/Gln), XPC (PAT) and LSCC. All blood samples of the Han people from the Guang Dong Zone was analysze with methods of PCR, PCR-RFLP, ASA and the technique of checking DNA sequencing with sequenator. We explored the association between polymorphisms and the clinical pathologic characteristic of LSCC. The data was compute with SPSS13.0. Odds Ratios (ORs) with 95% CI for relevancy intensity were calculated using binary logistic regression analysis. REULT: There is no difference of the frequency of XPC-PAT and XPD (751 Lys/Gln) genotype between in LSCC and in healthy contradistinguish (P > 0.05).@*CONCLUSION@#There may be no association between the susceptibility to laryngeal carcinoma and the genotype of XPC-PAT and XPD (751 Lys/Gln).

Association of the xeroderma pigmentosum group D DNA repair gene with hepatocellular carcinoma / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To 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.</p><p><b>METHOD</b>A 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.</p><p><b>RESULTS</b>Six 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).</p><p><b>CONCLUSION</b>Polymorphisms in the XPD codons 751 and 312 are not associated with HCC risk in the Chinese population.</p>

Relationship between single nucleotide polymorphism in repair gene XPD751 and prognosis in colorectal carcinoma patients / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate whether single nucleotide polymorphism (SNP) in DNA repair gene XPD751 is associated with sensitivity and time to progression (TTP) for platinum-containing combination chemotherapy in advanced colorectal carcinoma.</p><p><b>METHODS</b>A total of 98 patients pathologically diagnosed as advanced colorectal cancer were treated with FOLFOX chemotherapy. TheDNA of peripheral blood-leukocytes was obtained before treatment, and XPD genetype was detected by PCR-RFLP analysis.</p><p><b>RESULTS</b>The frequency of XPD751 Lys/lys was 76 cases (77.6%), lys/Gln 17 cases (17.4%), and Gln/Gln genetype 5 cases (5.1%). The effective rate of FOLFOX chemotherapy among patients with XPD751 Lys/lys was 50.0%, lys/Gln 29.4%, and Gln/Gln genetypes 20.0%. The difference between Lys/lys and lys/Gln was statistically significant, χ(2) = 4.04, P < 0.05. The results indicated that the failure of chemotherapy in patients with Lys/Lys genetype was 3.8-fold to those with Lys/Gln, by adjusting of gender, age, and tumor metastasis (OR = 3.800). The MTTP of the 98 patients was 10.1 months. The MTTP was 11.3 months for patients with Lys/Lys genotypes of XPD751 gene and 2.9 months for patients with Lys/Gln and Gln/Gln genotypes of XPD751 gene, the difference between Lys/Lys and at least one Gln was significant (P < 0.05).</p><p><b>CONCLUSIONS</b>Single nucleotide polymorphism of XPD751 correlates with the clinical response to FOLFOX chemotherapy. XPD751 genetic polymorphisms may be associated with TTP of advanced colorectal carcinoma patients treated with oxaliplatin as the first line chemotherapy. XPD751 genotype detected by the PCR-RFLP method may be a predictor of prognosis for FOLFOX chemotherapy.</p>

The association of XPD G312A polymorphism with lung cancer risk: a meta-analysis / 中国肺癌杂志

<p><b>BACKGROUND AND OBJECTIVE</b>It 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.</p><p><b>METHODS</b>The 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.</p><p><b>RESULTS</b>There 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).</p><p><b>CONCLUSION</b>XPD 312A allele is risk allele for lung cancer. Individuals with AA genotype have higher risk of lung cancer, especially in Asians.</p>

Casos clinicos: xeroderma pigmentoso / Clinical cases: xeroderma pigmentosum

El Xeroderma pigmentoso es una patología poco frecuente con incapacidad de las células para reparar el daño causado en el ADN por las radiaciones ultravioleta evidenciándose quemaduras solares, ampollas, costras telangiectasias, y queratosis, además de alteraciones neurológicas, retardo en el crecimiento pondo-estatural y en la maduración sexual.

Clone of human xeroderma pigmentosum group D cDNA and analysis of its expression and function / 生物医学工程学杂志

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.

Association of gene polymorphisms in the DNA repair gene XPD with risk of non-Hodgkin's lymphoma / 中国实验血液学杂志

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.

Early-onset of sporadic basal-cell carcinoma: germline mutations in the TP53, PTCH, and XPD genes

BACKGROUND: Basal cell carcinoma (BCC) is the most common non-melanoma skin cancer in the Western world. The objective of this study was to examine together germline mutations in the TP53, PTCH, and XPD genes as risk factors for developing BCC at a young age. We hypothesized that mutations in these genes significantly increase the risk of early-onset BCC (< or = 35 years). METHODS: The PCR, DNA sequencing and Restriction Fragment Length Polymorphisms methods were utilized to study eight Puerto Rican patients with a confirmed diagnosis of BCC before age 35. RESULTS: A novel germline mutation (T:A transversion) was identified at the exon 4, codon 50 of the TP53 gene of one BCC patient. No other mutations were found at the TP53 or PTCH genes. The presence of the XPD mutant allele is associated with a seven-fold increase in risk (OR = 7.0, p = 0.03) for developing BCC prior to age 35. In addition, the DNA Repair Capacity (DRC) of these BCC patients showed a 47% reduction that was significant in relation to age-matched controls (p = 0.021). However, the XPD mutant allele was not associated with the decrease in DRC observed in BCC participants. CONCLUSIONS: The evaluated population presented BCC before age 35, a phenomenon that is so rare as to make very difficult the study of this subpopulation with a larger sample size. The results of this study, suggest that the XPD Lys751Gln polymorphism may have a significant role in the development of early-onset BCC in the Puerto Rican population.

XRCC1 and XPD gene polymorphisms in a South Indian population.

DNA repair systems play an important role in maintaining the integrity of the human genome. Deficiency in the repair capacity due to either mutations or inherited polymorphisms in DNA repair genes may contribute to variations in the DNA repair capacity and subsequently susceptibility to cancer. The interindividual variability as well as ethnic differences in DNA repair polymorphisms, stress the importance to establish genotype profiles unique to a population. Hence the present study aimed to determine the frequencies of XRCC1 and XPD gene polymorphisms in 255 healthy random unrelated individuals from South India. DNA was isolated from the peripheral blood sample of these individuals and the XRCC1 and XPD genotypes were determined by PCR- RFLP with Msp1 and Pst1 enzymes respectively. The XRCC1 genotype frequencies revealed 36% Arg/Arg, 47% Arg/Gln and 17% Gln/Gln with Gln allele frequency of 0.41. Analysis of XPD genotypes revealed 51% Lys/Lys, 41% Lys/Gln and 8% Gln/Gln with Gln allele frequency of 0.29. No significant difference in the distribution of genotypes was seen based on gender. Comparison of the frequencies of XRCC1 and XPD polymorphisms observed in the present study with other populations revealed a distinctive nature of the South Indian population. An understanding of DNA repair gene polymorphisms might not only enable risk assessment of humans exposed to environmental carcinogens but also response to therapy, which target the DNA repair pathway.

Association of genetic polymorphism of XPD with chromosomal damage in workers exposed to radiation / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To explore association genetic polymorphism of XPD with chromosomal damage in workers exposed to radiation.</p><p><b>METHODS</b>182 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).</p><p><b>RESULTS</b>The 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).</p><p><b>CONCLUSION</b>XPD 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.</p>

Analysis for the association between genetic polymorphisms of XRCC1, XPD, XRCC3, CCND1 and the latency of the occupational chronic benzene poisoning / 中华预防医学杂志

<p><b>OBJECTIVE</b>To explore the association between genetic polymorphisms of XRCC1, XPD, XRCC3 and CCND1 and latency of occupational chronic benzene poisoning.</p><p><b>METHODS</b>80 patients diagnosed with occupational chronic benzene poisoning were investigated. PCR-RFLP was applied to detect the single nucleotide polymorphisms of C26304T, G27466A, G28152A, G36189A of XRCC1, C22541A, C23591T, A35931C of XPD, C18067T of XRCC3 and G870A of CCND1. Their relationship with the latency of chronic benzene poisoning was analyzed by Kaplan-Meier method.</p><p><b>RESULTS</b>The association of XRCC1 G27466A subgroup with the latency of chronic benzene poisoning was observed, as well as that of CCDN1G870A subgroup. The benzene-exposed workers with XRCC1 27466G/G homozygous wild genotype developed chronic benzene poisoning 6.9 years later than those had homozygous (27466A/A) or heterozygous (27466G/A) mutant alleles. On the other hand, the latency developing chronic benzene poisoning was longer in workers with homozygous (CCND1 870A/A) or heterozygous (CCND1 870G/A) mutant alleles than in those carrying 870G/G homozygous wild genotype (14.9 vs. 8.7 years).</p><p><b>CONCLUSION</b>The polymorphisms of XRCC1 and CCND1 potentially modify the latency of the chronic benzene poisoning among workers exposed to benzene.</p>

Association between genetic polymorphism in xeroderma pigmentosum G gene and risks of laryngeal and hypopharyngeal carcinomas / 中国医学科学院学报

<p><b>OBJECTIVE</b>To study the association between polymorphism of DNA repair gene xeroderma pigmentosum G (XPG) Asp1104His and the risks of developing laryngeal and hypopharyngeal carcinomas.</p><p><b>METHODS</b>Totally 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.</p><p><b>RESULTS</b>Compared 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 ).</p><p><b>CONCLUSION</b>The XPG Asp1104His polymorphism may play a role in the development of laryngeal and hypopharyngeal carcinomas.</p>

XRCC1 and XPD genetic polymorphisms predict clinical responses to platinum-based chemotherapy in advanced non-small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>DNA repair system plays an important role in tumor sensitivity to platinum-based chemotherapy. The purpose of this study was to examine the association between polymorphisms in XRCC1 and XPD, which are involved in DNA repair, and clinical responses to platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>XRCC1 Arg194Trp and XPD Lys751Gln were genotyped by PCR-RFLP method in 200 patients with advanced NSCLC who received platinum-based chemotherapy. Unconditional logistic regression model was used to analyze the association between genetic polymorphisms and clinical responses.</p><p><b>RESULTS</b>The overall response rate (CR + PR) was 36.0%, including 1 CR, 72 PR, 94 SD and 34 PD. The XRCC1 194Trp allele carriers had higher response rate than the subjects with the Arg/Arg genotype (adjusted OR, 2.48; 95% CI, 1.36 - 4.51, P = 0.003). However, the XPD Lys751Gln polymorphism was not found to be associated with the platinum-based chemotherapy. These two genetic polymorphisms may have some interaction in the drug sensitivity, the P value for the trend was significant (P = 0.004).</p><p><b>CONCLUSION</b>Those results suggest that the XRCC1 Arg194Trp and XPD Lys751Gln genetic polymorphisms may be associated with clinical responses to platinum-based chemotherapy in advanced non-small cell lung cancer.</p>

Association between polymorphisms of XPD gene and susceptibility to chronic benzene poisoning / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To explore the relationship between genetic polymorphisms of XPD gene and susceptibility to chronic benzene poisoning.</p><p><b>METHODS</b>A case control study was conducted. Eighty patients diagnosed with chronic benzene poisoning and 62 workers occupationally exposed to benzene who were engaged in the same working time and job title as patients were investigated. PCR-RFLP was used for detecting the single nucleotide polymorphisms (SNPs) on codon156, codon312 and codon751 of XPD gene.</p><p><b>RESULTS</b>There was a 2.903 times (95% CI: 1.054 - 7.959, P = 0.039 2) increased risk of chronic benzene poisoning in the subjects carrying XPD 751Gln variant allele compared with those carrying XPD 751Lys/Lys genotype, after adjusted for sex, length of service, smoking and drinking status.</p><p><b>CONCLUSION</b>The subjects with XPD 751Gln variant allele are more susceptive to benzene.</p>

Enhancing alkylating agent resistance through ERCC2 gene transfection in human glioma cell line / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To confirm the enhancing effect of excision repair cross complementing rodent repair deficiency gene 2 (ERCC2) on alkylating agents resistance.</p><p><b>METHODS</b>The 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.</p><p><b>RESULTS</b>The 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.</p><p><b>CONCLUSION</b>The 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.</p>

Association of genetic polymorphisms in the DNA repair gene XPD with risk of lung and esophageal cancer in a Chinese population in Beijing / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>XPD polymorphisms at Asp312Asn and Lys751Gln sites have been shown to modulate DNA repair capacity. The authors therefore assessed the relationship between these XPD polymorphisms and susceptibility to lung and esophageal cancer in a Chinese population via a hospital-based, case-control study.</p><p><b>METHODS</b>Genotypes were determined by PCR-restriction fragment length polymorphism approaches in 383 healthy controls, 351 patients with lung cancer, and 325 patients with esophageal squamous cell carcinoma (SCC). The adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariate logistic regression.</p><p><b>RESULTS</b>Individuals carrying at least one 312Asn variant allele (Asp/Asn and Asn/Asn genotypes) were at an increased risk for lung SCC as compared with those with the Asp/Asp genotype (OR 1.80; 95% CI: 1.10-2.93; adjusted for age, sex and smoking), but this increased risk was not observed among patients with adenocarcinoma of the lung (adjusted OR: 1.07; 95% CI: 0.55-2.08). Furthermore, stratified analysis indicated a multiplicative interaction between tobacco smoking and the variant XPD 312Asn and 751Gln alleles on risk of lung SCC. The ORs of lung SCC for the variant XPD 312Asn and 751Gln alleles with smoking>or=29 pack/year were 12.44 (95% CI: 4.97-31.17) and 10.74 (95% CI: 4.51-25.57), respectively. No significant association between the Asp312Asn or Lys751Gln polymorphism and the risk of esophageal cancer was found.</p><p><b>CONCLUSION</b>The above findings indicate that the Asp312Asn and Lys751Gln polymorphisms in the XPD locus are associated with the risk of lung SCC but not lung adenocarcinoma or esophageal SCC in this Chinese population.</p>