Relationship between XPD, RAD51, and APEX1 DNA repair genotypes and prostate cancer risk in the male population of Rio de Janeiro, Brazil

Abstract Susceptibility to cancer ensues in individuals carrying malfunctioning DNA repair mechanisms. The impact of Single Nucleotide Polymorphisms (SNPs) in key DNA repair mechanisms on risk for prostate cancer was investigated in this case-control study. Samples consisted of 110 patients with confirmed prostate cancer and 200 unaffected men, from Rio de Janeiro, Brazil. XPD/Lys751Gln (rs13181), APEX1/Asp148Glu (rs1130409), and RAD51/G135C (rs1801320) SNPs were analyzed by PCR-RFLP. Allelic and genotypic frequencies were calculated and compared by Chi-Square test. The association between SNPs and clinical/epidemiological data was considered significant by Odds Ratio analysis, with IC95% and a p-value≤0.05. Only the XPD/Lys751Gln SNP significantly increased susceptibility to disease in southeastern Brazilian men, with p≤0.001 [OR=2.36 (1.46-3.84)], with no association with APEX1 or RAD51 SNPs. Combined XPD+RAD51 SNPs were highly associated with the disease, p≤0.005 [OR=3.40 (1.32-9.20)]. A Chi-Square significant association between XPD/Lys751Gln and Gleason score was also observed (OR=9.31; IC95%=1.19-428.0; p=0.022). Epidemiological inquiries revealed that exposure to pesticides significantly impacted the risk for prostate cancer in this population. DNA repair dysfunctions seem to prevail among workers exposed to chemical byproducts to cancer in this specific tissue. Non-invasive genotyping SNPs may help assessment of prostate cancer risk in environmentally exposed populations.

Genetic polymorphisms of DNA repair genes XPD, XPC, and XRCC4 in relation to colorectal cancer susceptibility / 中国肿瘤临床

Objective:To investigate the association of XPD rs13181 (codon751A/C, Lys751Gln), rs238406 (codon156C/A, Arg156Arg), XPC rs2279017 (i11C/A), and XRCC4 rs3734091 (codon247T/C, Ala247Ser) polymorphisms with colorectal cancer (CRC) susceptibility. Methods:A total of 338 patients with CRC who were treated at the Beijing Cancer Hospital from April 2013 to January 2016 (case group) and 315 healthy controls (control group) were genotyped using TaqMan technology. Results:The genotype GT and G alleles of XPD rs13181 increased the risk of CRC (GT>TT, adjusted OR=1.69, 95%CI=1.15-2.47, P=0.007;G>T, adjusted OR=1.77, 95%CI=1.19-2.64, P=0.005). The genotype GT and T alleles of XRCC4 rs3734091 increased the susceptibility of CRC (GT>GG, adjusted OR=9.02, 95%CI=5.61-14.50, PG, adjusted OR=4.06, 95%CI=2.49-6.61, P<0.001). Analyses of XPD rs13181 and rs238406 indicated that the haplotype GT significantly decreased the risk of CRC (adjusted OR=0.39, 95%CI=0.18-0.85, P=0.018). Moreover, the combinations of the XPC rs2279017 G allele and the XRCC4 rs3734091 T allele (adjusted OR=28.43, 95%CI=6.85-117.95, P<0.001) and the XPD rs13181 G allele and the XRCC4 rs3734091 T allele (adjusted OR=10.24, 95%CI=4.69-22.35, P<0.001) exhibited significantly increased CRC risk. Conclusion:The polymorphisms of XPD rs13181 and XRCC4 rs3734091 increased the risk of CRC.

Association between ERCC2/XPD Polymorphisms and UVC-induced DNA Damage Using Transfected Cells Model / 中国医科大学学报

Objective To explore the function of ERCC2/XPD polymorphisms in the repair of DNA damage induced by UVC. Methods Plas?mids stably expressing ERCC2/XPD rs13181 AA(Lys751)and ERCC2/XPD rs13181 CC(Gln751)were transfected into Chinese hamster ovary cells,and the stable ERCC2 transfected cell lines were obtained. MTT assay was used to compare the inhibitory rates of the transfected cells treated with UVC at different irradiation intensity. The DNA damage repair ability of the transfected cells treated with UVC for 1,3,6 and 24 h was detected by modified comet assay. Results Compared with UV5ERCC2(CC),UV5ERCC2(CC) was more sensitive to UVC with decreased cell viability. DNA damage level of UV5ERCC2(CC) cells was more serious than UV5ERCC2(CC). Conclusion DNA repair capacity of ERCC2/XPD rs13181A allelic is lower than its wild?type,suggesting that ERCC2/XPDpolymorphisms play a critical role in UVC?induced DNA damage repair.

Correlation of Clinical Efficacy of XPD Gene Polymorphisms and Platinum-based Chemotherapy in Ad-vanced Non-small Cell Lung Cancer:A Meta-analysis / 中国药房

OBJECTIVE:To systematically review the relationship of clinical efficacy between XPD Lys751Gln (A/C),XPD Asp312Asn(G/A)and platinum-based chemotherapy in patients with advanced non-small cell lung cancer(NSCLC),and provide evidence-based reference for clinical treatment. METHODS:Retrieved from PubMed, Cochrane Library, EMBase, Medline, CJFD,VIP database and WanFang database,studies about the effects of XPD Lys751Gln and XPD Asp312Asn polymorphism on ef-fectiveness,clinical outcomes and adverse drug reaction of platinum-based chemotherapy in advanced NSCLC patients were collect-ed,and Meta-analysis was performed by using Rev Man 5.3 software. RESULTS:Totally 30 studies were included,involving 5 028 patients. Genetic testing showed that XPD Lys751Gln divided into mutant gene (Lys/Gln + Gln/ Gln) and wild-type gene (Lys/Lys),while XPD Asp312Asn divided into mutant gene (Asp/Asn + Asn/Asn) and wild-type gene (Asp/Asp). Results of Me-ta-analysis showed,the progression-free survival (PFS) of Lys/Gln+Gln/Gln patients with platinum in XPD Lys751Gln polymor-phism was obviously lower than Lys/Lys patients [OR=-1.12,95%CI(-1.73,-0.50),P<0.001],while there was no significant difference in the chemotherapy effectiveness and total survival period. The effective rate of Asp/Asn+Asn/Asn patients for platinum in XPD Asp312Asn polymorphism was lower than Asp/Asp patients [OR=0.80,95%CI(0.68,0.96),P=0.02],while there was no significant difference in the total survival period and PFS. Meanwhile,the incidence of Ⅲ-Ⅳ level gastrointestinal adverse reac-tions of Lys/Gln+Gln/Gln with platinum in XPD Lys751Gln polymorphism was higher than Lys/Lys patients [OR=0.43,95%CI (0.20,0.94),P=0.03],and there was no significant difference in Ⅲ-Ⅳ level blood system adverse reactions. CONCLUSIONS:XPD Lys751Gln polymorphism may be associated with PFS and Ⅲ-Ⅳ level gastrointestinal adverse reactions for advanced NSCLC patients with platinum-based chemotherapy,while XPD Asp312Asn polymorphism may have effect on platinum-based chemotherapy,both of them may be as estimate the chemotherapy effect and prognosis detection index of platinum-based chemo-therapy.

Avaliação de polimorfismos funcionais nos genes de reparo XRCC1, APEX1, XPD e XPF em carcinomas de células escamosas orais / Evaluation of functional polymorphisms in the repair genes XRCC1, APEX1, XPD and XPF in oral squamous cell carcinomas

As vias de reparo por excisão de base (BER) e por excisão de nucleotídeo (NER) desempenham um papel crucial na manutenção da integridade genômica. Polimorfismos em genes das vias BER e NER, que modulam a capacidade de reparo do DNA, podem estar relacionados ao risco de desenvolvimento e prognóstico do câncer oral. O presente trabalho teve como objetivo investigar a frequência de polimorfismos de nucleotídeos simples, em dois genes da via de reparo do DNA por excisão de base (XRCC1 ­ rs25487 e APEX1 ­ rs1130409) e dois genes da via de reparo por excisão de nucleotídeo (XPD ­ rs13181 e XPF ­ rs1799797), em pacientes com carcinoma de células escamosas oral (CCEO), buscando associações com o risco de desenvolver esta neoplasia maligna e o seu prognóstico. Um total de 92 amostras de DNA de pacientes com CCEO e 130 controles foram genotipadas utilizando o método da reação em cadeia da polimerase em tempo real. O software estatístico GraphPad Prism version 6.0.1. foi utilizado para a aplicação dos testes apropriados. Odds ratio (OR) e hazard ratio (HR), e seus intervalos de confiança (IC) de 95%, foram calculados pela regressão logística. A avaliação do prognóstico foi realizada por meio da curva de Kaplan-Meier e análise multivariada de Cox. A presença das variantes polimórficas nos genes XRCC1, APEX1, XPD, e XPF não foram associadas ao risco de desenvolver CCEO. A interação da presença da variante polimórfica com o hábito de fumar não foi significativa para nenhum dos polimorfismos analisados. Já a presença do polimorfismo em XPD, somada ao hábito de beber, aumentou o risco de desenvolver CCEO (OR 1,86, 95% IC: 0,86 ­ 4,01, p=0,03). Apenas o SNP do APEX1 (rs1130409) esteve associado a uma diminuição da sobrevida específica (HR 3,94, 95% IC: 1,31 ­ 11,88, p=0,01). O presente estudo sugere uma interação entre o consumo de álcool e a presença do polimorfismo estudado no gene XPD. Além disso, indica um pior prognóstico para pacientes que possuem o polimorfismo estudado em APEX1 (AU).

Base excision repair (BER) and nucleotide excision repair (NER) pathways play critical role in maintaining genome integrity. Polymorphisms in BER and NER genes which modulate the DNA repair capacity may affect the susceptibility and prognosis of oral cancer. This study was conducted with genomic DNA from 92 patients with oral squamous cell carcinomas (OSCC) and 130 controls. The cases were followed up to explore the associations between BER and NER genes polymorphisms and the risk and prognosis of OSCC. Four single-nucleotide polymorphisms (SNPs) in XRCC1 (rs25487), APEX1 (rs1130409), XPD (rs13181) and XPF (rs1799797) genes were tested by polymerase chain reaction ­ quantitative real time method. The GraphPad Prism version 6.0.1 statistical software was applied for statistical analysis of association. Odds ratio (OR), hazard ratio (HR), and their 95 % confidence intervals (CIs) were calculated by logistic regression. Kaplan-Meier curve and Cox proportional hazard model were used for prognostic analysis. The presence of polymorphic variants in XRCC1, APEX1, XPD and XPF genes were not associated with an increased risk of OSCC. Gene-environment interactions with smoking were not significant for any polymorphism. The presence of polymorphic variants of the XPD gene in association with alcohol consumption conferred an increased risk of 1.86 (95% CI: 0.86 ­ 4.01, p=0.03) for OSCC. Only APEX1 was associated with decreased specific survival (HR 3.94, 95% CI: 1.31 ­ 11.88, p=0.01). These results suggest an interaction between polymorphic variants of the XPF gene and alcohol consumption. Additionally APEX1 may represent a prognostic marker for OSCC (AU).

Avaliação de polimorfismos nos genes XPD e XRCC3 em carcinomas orais de células escamosas / Evaluation of polymorphisms in the XPD and XRCC3 genes in oral squamous cell carcinomas

O carcinoma oral de células escamosas (COCE) é importante causa de morbidade e mortalidade em todo o mundo a despeito dos recentes avanços nas formas de tratamento. Diante disto, várias são as pesquisas no intuito de se encontrar marcadores que possam melhorar a avaliação do prognóstico desta doença. Neste sentido têm se destacado os estudos dos polimorfismos genéticos, os quais podem influenciar a suscetibilidade individual para o desenvolvimento do câncer. O objetivo deste estudo foi avaliar a associação entre a frequência dos polimorfismos XPD Lys751Gln e XRCC3 Thr241Met e o perfil clinicopatológico em casos de COCE, incluindo idade, sexo, presença ou não de metástase e gradação histológica de malignidade de Bryne (1998). A amostra foi composta por 54 casos de COCE e 40 casos de hiperplasia fibrosa inflamatória (HFI). Os casos de COCE foram classificados como lesões de baixo ou de alto grau de malignidade. Foram utilizadas amostras de DNA previamente extraído de blocos de parafina. Os genótipos para cada caso foram determinados através da técnica de PCR-RFLP (reação em cadeia da polimerase - polimorfismos de comprimento de fragmentos de restrição). Os resultados foram submetidos aos testes estatísticos Exato de Fisher e Quiquadrado de Pearson e foi calculada a razão de chance (odds ratio) considerando o nível de significância quando p<0,05. Para o XPD, o genótipo Lys/Gln foi mais comum nas HFIs (n=28; 70%) que nos COCEs (n=24; 44,4%) (OR: 0,3; p<0,05). A frequência do alelo Gln foi maior nas lesões de alto grau, em comparação às de baixo grau (0,48 e 0,21, respectivamente) (OR: 3,4; p<0,05). Para o XRCC3, o alelo Met foi mais frequente no COCE que na HFI (0,49 e 0,35, respectivamente) (OR: 2,6; p<0,05). O genótipo Met/Met foi associado à presença de metástases (OR: 8,1; p<0,05). Não houve associação estatística significativa entre os genótipos e a idade ou sexo dos pacientes. Na amostra analisada, a maior frequência do alelo XPD Gln na HIF revela um possível papel protetor dessa variante contra o desenvolvimento do COCE. Todavia, sua associação com lesões de alto grau, indica que esse alelo poderia influenciar no processo de progressão após o tumor instalado. A presença do alelo XRCC3 Met, por sua vez, parece contribuir com o desenvolvimento do COCE e de metástases nessas lesões. (AU)

Oral squamous cell carcinoma (OSCC) is an important cause of morbidity and mortality worldwide despite recent advances in treatment. There are several studies aiming to find markers that may improve the assessment of this disease prognosis. Studies about genetic polymorphisms have gained prominence due to their influence on individual susceptibility to cancer development. The aim of this study was to evaluate the association between the frequency of polymorphisms XPD Lys751Gln and XRCC3 Thr241Met and clinicopathological features of OSCC cases, including age, sex, presence or absence of metastases, and histological grading of malignancy according to Bryne (1998). Sample consisted of 54 cases of OSCC and 40 cases of inflammatory fibrous hyperplasia (IFH). OSCC cases were classified as low or high grade. DNA samples were previously extracted from paraffin blocks. Genotypes for each case were determined through PCR-RFLP (polymerase chain reaction - restriction fragment length polymorphism). Results were analyzed by Fisher's exact test and Chi-square test and the odds ratio was calculated considering p < 0.05 to indicate statistical significance. For XPD, Lys/Gln genotype was more common in IFHs (n=28; 70%) than in OSCCs (n=24; 44.4%) (OR: 0.3; p<0.05). Frequency of Gln allele was higher in high-grade lesions when compared to low grade lesions (0.48 and 0.21, respectively) (OR: 3.4; p<0.05). For XRCC3, Met allele was more common in OSCC than in IFH (0.49 and 0.35, respectively) (OR: 2.6; p<0.05). Met/Met genotype was associated with presence of metastases (OR: 8.1; p<0.05). There was no statistically significant association between the genotypes and the age or sex of patients. In the present sample, the higher frequency of XPD Gln allele in IFH reveals a possible protective role of this variant against the development of OSCC. However, its association with high-grade lesions indicates that this allele could influence the tumor progression after the neoplasia development. The presence of XRCC3 Met allele, in turn, seems to contribute to the development of OSCC and metastases. (AU)

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 relationship between polymorphism of genes XPA, XPC, XPD, XRCC1 and susceptibility to acute lymphoblastic leukemia / 中华内科杂志

ObjectiveTo study the relationship between polymorphism of genes XPA, XPC, XPD,XRCC1 and susceptibility to acute lymphoblastic leukemia (ALL) in a Chinese population.Methods Polymorphism were determined by a case-control study through matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry method of Mass-ASSAY platform in 114 confirmed ALL cases and 169 age- and sex- matched controls, so as to compare the relationship between differert genotypes and ALL risk.ResultsMultivariate logistic regression analysis revealed that individuals carrying at least one 23G variant allele(AG/GG genotypes) had a significantly increased risk for ALL (adjusted OR 2.02; 95％ CI 1.08-3.78) compared with the wild-type genotype (23 AA), and evidence that positive interactions between the polymorphisms in XPC C499T and XPA A23G might occur.Furthermore, individuals with both putative risk genotypes had a significantly higher risk (adjusted OR 5.60; 95％ CI 1.57-19.90), compared with those with both wild-genotypes. By contrast, no significant association was observed between the XPD T751G, XRCC1 G399A, C194T pelymorphism and ALL risk.ConclusionsXPA A23G and XPC C499T polymorphism may contribute to the risk of developing ALL.There are significant combinations between XPC C499T and XPA A23G.

Screening for XPD312 polymorphisms in human oral cancer: a preliminary study

Xeroderma pigmentosum-D (XPD) is one of the genes that play a role in the Nucleotide-Excision Repair (NER). Polymorphisms in XPD gene have been identified and reported to be associated with many types of cancer with two common single nucleotide polymorphisms (SNPs), namely, XPD312 and XPD751. The XPD312 polymorphism is at exon 10 codon 312 Asp to Asn (A→G) and the association of this polymorphism with oral cancer is very little known, especially, in Malaysia. The aim of this study was to screen for XPD312 gene polymorphisms in human oral cancer patients attending Hospital Universiti Sains Malaysia (HUSM), Malaysia. Blood samples were collected from 10 oral cancer and 10 normal healthy subjects with their consent. DNA was extracted using commercial DNA extraction kit and Polymerase Chain Reaction (PCR) was performed to amplify the XPD312 gene. The PCR products were digested using restriction enzyme, Sty I and analyzed on a 3% agarose gel for the detection of polymorphisms. This was followed by DNA sequencing to confirm the findings. In the current study, only homozygous wild type polymorphisms in the XPD312 gene was noticed in the oral cancer tissues as revealed by the restriction enzyme and DNA sequencing analyses.

Relationship between XPD Lys751Gln polymorphisms and the risk of adult acute leukemia / 白血病·淋巴瘤

Objective To detect the relationship between XPD Lys751Gln polymorphism and the risk of adult acute leukemia (AL). Methods 100 adult AL patients and 100 controls were chose as case and Lys751Gln were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) analysis in peripheral blood. Results The genotype frequency of Lys/Lys, Lys/Gln, Gln/Gln were 83 %, 16 %, 1% in case group and 90 %, 10 %, 0 in control group, respectively. The difference the two groups was no signficant difference (x2=1.44, P =0.49). No significantly increased risk for adult AL was observed for those carrying variant genotype with OR analysis (x2 = 2.10, P =0.15, OR =1.84; 95 % CI 0.80-4.25). Individuals with the variant genotype of XPD Lys751Gln might enhance the risk of adult AL (OR =2.77, 95 % CI 0.99-7.73). Conclusion XPD Lys751Gln polymorphism is found to have relationship with adult acute lymphocytic leukemia.

Relationship of ERCC1, XPD, and BRCA1 polymorphisms with efficacy of platinum-based chemotherapy for patients with advanced non-small cell lung cancer / 第二军医大学学报

Objective: To investigate the relationship of excision repair cross-complementing 1 (ERCC1), xeroderma pigmentosum group D(XPD), and breast cancer susceptibility gene 1 (BRCA1) polymorphisms with the efficacy of platinum-based chemotherapy for treatment of the patients with advanced non-small cell lung cancer. Methods: A total of 124 patients with advanced NSCLC were routinely treated with platinum-based chemotherapy, and their clinical responses were evaluated. ERCC1 Asn118Asn(rs11615), XPD Lys751Gln(rs13181) and BRCA1 Ser1613Gly(rs1799966) of the patients were genotyped using the TaqMan method. The association of ERCC1 Asn118Asn, XPD Lys751Gln and BRCA1 Ser1613Gly polymorphisms with the patient responses was analyzed using unconditional logistic regression model. Results: It was found that the BRCA1 Ser1613Gly polymorphism was significantly correlated with clinical benefit(P = 0. 014). Patients carrying Gly allele had better clinical benefit than patients with wildtype allele(P = 0. 006). No significant association was found between ERCC1 and XPD polymorphisms with clinical benefit. Furthermore, we found that the three SNPs in NER(nucleotide excision repair) could work together. More variant alleles(ERCC1 T, XPD Gln and BRCA1 Gly) was associated with better clinical benefit(P = 0. 036). Conclusion: The BRCA1 Ser1613Gly polymorphism of NER is associated with the clinical benefit of NSCLC patients receiving platinum-based chemotherapy. Analysis of SNPs of more genes may help to guide drug choosing for chemotherapy.

XPD Polymorphisms and Risk of Squamous Cell Carcinoma of the Head and Neck in a Korean Sample

OBJECTIVES: XPD is a major player in nucleotide excision repair, which is one of the basic pathways of DNA repair. The objective of this study was to investigate the association of XPD single nucleotide polymorphisms (SNPs) and the risk of squamous cell carcinoma of the head and neck (SCCHN) in Koreans. METHODS: We performed XPD +23591G>A and +35931A>C genotyping in 290 SCCHN patients and 358 controls. RESULTS: The frequencies of the XPD +23591G>A (GG/GA/AA) genotypes were 89.0%/11.0%/0% in the patients and 90.3%/8.8%/0.9% in the controls, respectively. The odds ratio (OR) of the XPD +23591 GA genotype was 1.94 (0.92 to 4.08) in reference to the GG genotype. The frequencies of the XPD +35931A>C (AA/AC/CC) genotypes were 86.9%/12.0%/1.1% in the patients and 85.6%/13.8%/0.6% in the controls, respectively. The OR of the XPD +35931 AC and CC genotypes were 0.98 (0.51 to 1.88) and 2.68 (0.71 to 10.1), respectively, in reference to the AA genotype. On the subgroup analyses according to the smoking and drinking statuses, the SNPs and haplotypes of XPD showed no statistically significant association with the risk of SCCHN. CONCLUSION: The results of this study suggest that the XPD +23591G>A and +35931A>C SNPs are not associated with the risk of SCCHN in Koreans; however, a further study with a larger number of subjects is necessary to verify this conclusion.

Study on the relationship between hepatocellular carcinoma and the interaction between polymorphisms in DNA repair gene XPD and environmental factors / 中华流行病学杂志

Objective To study the relationship between hepatocellular carcinoma and the interaction of polymorphisms in DNA repair gene XPD with environmental factors. Methods A hospital-based ease-control study on hepatoeellular carcinoma was conducted. All the hepatocellular carcinoma eases (n=300) were newly diagnosed and controls (n=312) were diagnosed with non-tumor cases. XPD genotype (Lys751 Gin and Asp312 Ash) from blood derived DNA was determined using TaqMan MGB Real-time PCR. Unconditional logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). Results For XPD condon 751 genotypes, there was no significant difference between frequencies of the AC or CC among patients and controls (P>0.05) (referent AA). The frequency of XPD312A allelic gene was higher in eases than that in controls and was associated with an increased risk (adjusted OR = 2.62,95% CI: 1.626-4.222) for hepatocellular carcinoma when compared with GG genotype. Interactions were found between infection of HBsAg and XPD312 (OR=7.348), as well as between smoking and non-wild type gene of XPD751 (0R=4.291) and XPD312 (OR=5.341). Conclusion DNA repair XPD312A allelic gene might increase the risk of Hepatocellular carcinoma. Interactions between HBsAg infection, smoking and XPD were observed in Hepatocellular carcinoma.

Polymorphisms in ERCC1 and ERCC2/XPD and Survival in Non-Small-Cell Lung Cancer Patients Treated with Cisplatin Based Chemotherapy

PURPOSE: The expressions of low levels of ERCC1 (excision repair crosscomplementation group 1) and ERCC2/XPD (excision repair cross- complementation group 2) have been studied in order to find a potential marker for predicting the prognosis or treatment response in cancer patients. However, polymorphisms in these genes have been rarely evaluated in terms of predicting the survival of cancer patients. MATERIALS AND METHODS: We investigated whether these polymorphisms had an effect on the response to chemotherapy and on the survival in 109 patients, with non-small-cell lung cancer, treated with cisplatin plus gemcitabine, paclitaxel or docetaxel. The polymorphisms of ERCC1 Asn118Asn (C->T), ERCC2 Lys751Gln and Asp312Asn were evaluated using a SNaPshot kit. RESULTS: The treatment responses showed no statistically significant differences according to the polymorphisms of ERCC1 Asn118Asn, ERCC2 Lys751Gln or Asp312Asn. The median survival time was 376 days (95% CI, 291~488). The overall survival rate showed no significant difference according to age, sex, chemotherapy regimen, clinical stage or sequential radiation therapy. The polymorphisms of ERCC2 Lys751Gln and Asp312Asn did not affect the survival of the patients (p=0.4711 and 0.4542, respectively). The polymorphism of ERCC1 Asn118Asn, chemotherapy response, performance status and body weight loss had effect on the overall survival of the patients (p=0.0001, 0.0001, 0.0176 and 0.0082 respectively). As for survival rate, according to the polymorphism in ERCC1 Asn118Asn, the median survival time in those patients showing the wild genotype (C/C) was 480 days (95% CI, 333~544), which was statistically significant compared with the 281 days for the patients with the variant genotype (T/T, C/T) (hazard ratio 3.497) (95% CI, 214~376). CONCLUSION: It is suggested that the presence of the wild genotype in ERCC1 Asn118Asn, in non-small-cell lung cancer patients treated with cisplatin based chemotherapy, was a surrogate marker for predicting a better survival.