• Asian Pacific Journal of Cancer Prevention
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• v.15 no.10
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• pp.4117-4123
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• 2014

Background: To determine prognostic value of excision repair cross-complementation 1 (ERCC1) in patients with malignant pleural mesothelioma (MPM). Materials and Methods: The study included 60 patients with MPM who were diagnosed and treated in the Radiation Oncology Department of Kayseri Teaching Hospital and Medical Oncology Department of Erciyes University, Medicine School between 2005 and 2013. By using immunohistochemical methods, ERCC1 expression in biopsy specimens was evaluated. We retrospectively assessed whether there is a correlation between ERCC1 and response to anti-neoplastic therapy or survival. Results: There were 50 men and 10 women with median age of 62 years (range: 39-83). Histological type was epithelial mesothelioma in the majority of the cases (85%), most commonly presenting in stage four. Of the cases, 20 (33%) received radiotherapy, 60 (%100) received first-line chemotherapy and 15 (%25) received second-line chemotherapy. In the assessment after therapy, it was found that there was partial response in 12 cases (20%), stable disease in 19 cases (31.4%) and progression in 25 cases (41.7%). ERCC1 was positive in 43% of the cases. Mean OS was 11.7 months and mean DFS was 9.5 months in ERCC1-positive cases regardless of therapy, while they were 19.2 months and 17.1 months in ERCC1-negative cases, respectively. The difference was found to be significant (p<0.05). In univariate analysis, stage, comorbidity, response to treatment and ERCC1 expression were found to be significantly associated with OS (p=0.083; p=0.043; p=0.041; p=0.050). In multivariate analysis, response to treatment remained to be significant for OS (p=0.005). In univariate and multivariate analyses, response to treatment and ERCC1 were found to be significantly associated with DFS (p=0.049; p=0.041). Conclusions: ERCC1 was identified as poor prognostic factor in patients with MPM.

• Tuberculosis and Respiratory Diseases
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• v.60 no.2
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• pp.151-159
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• 2006

Background : Excision repair cross complementing gene 1 (ERCC1) not only has a protective role against carcinogens, but plays an important role in cisplatin-resistance via the repair of cisplatin-DNA adducts. This study investigated the association between the ERCC1 expression levels in sputum and survival after cisplatin-based chemotherapy in patients with inoperable non-small cell lung cancer (NSCLC). Methods : Using the sputum collected from 67 inoperable (stage IIIa-IV) NSCLC patients treated with either taxanes (33 cases) or gemcitabine (34 cases) plus cisplatin, the relative expression levels of ERCC1 and the expression of the tumor specific antigen, MAGE, were examined by the quantitative RT-PCR and RT-PCR, respectively. The response and survival were compared with the relative level of ERCC1 or MAGE expression and the treatment modality. Results : In the sputum, ERCC1 and MAGE was detected in 74.6% and 40.2% of patients, respectively. Using the median ERCC1 level, the patients were classified as having high or low ERCC1 expression. The median overall survival (MST) was significantly longer in patients with a high ERCC1 expression level than those with a low expression level (84 weeks vs. 44 weeks respectively, P=0.017). In the taxene-based treatment group, the MST was longer than the gemcitabine group (79 weeks vs. 47 weeks, respectively, P=0.03). The levels of ERCC1 were significantly higher in patients who were MAGE-positive (P=0.003). In the MAGE-negative patients, the MST was longer in the high ERCC1 group (103 weeks vs. 43 weeks, P=0.008), but not in the MAGE-positive patients (62 weeks vs. 44 weeks, P=0.348). Conclusion : ERCC1 expression in the sputum can be a prognostic factor for survival after chemotherapy in patients with inoperable NSCLC.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.2049-2052
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• 2013

The effects of polymorphisms in ERCC5, ERCC6, XPC, CCNH and MMS19L on osteosarcoma response to chemotherapy and the survival of the affected patients were assessed. Genotyping of ERCC5, ERCC6, XPC, CCNH and MMS19L was performed by PCR-RFLP assay. The median PFS was 12.8 months, and the median OS was 18.6 months. Individuals carrying homozygous genotypes of ERCC5 rs17655 and ERCC5 rs1047768 were more like to have good response to treatment, while those carrying homozygous genotypes of MMS19L rs29001322 showed poor response. Osteosarcoma patients carrying TT genotype of ERCC5 rs1047768 showed a significantly longer PFS (16.8 months) and OS (21.4 months) than CC genotype, with HRs(95% CI) of 0.31 (0.10-0.93) and 0.32 (0.06-0.97), respectively. Conversely, those with the TT genotype of MMS19L rs29001322 demonstrated shorter PFS and OS, the HRs (95% CI) being 2.23 (1.08-4.15) and 4.62 (1.45-16.08), respectively. Our findings showed polymorphisms in ERCC5 rs1047768 and MMS19L rs29001322 to be associated with clinical outcome of osteosarcoma patients undergoing chemotherapy.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5883-5886
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• 2012

Osteosarcoma is the most common primary bone malignancy in children and adolescents, and its clinical outcome is poor. We evaluated the response of GSTP1, ERCC1 and ERCC2 to chemotherapy among osteosarcoma patients, and the role of these genes on the prognosis of osteosarcoma. 187 patients with osteosarcoma were administered with methotrexate, cisplatin/adriamycin, actinomycin D, cyclophosphamide, or vincristine treatment. GSTP1, ERCC1 and ERCC2 polymorphism was genotyped by PCR-RFLP assay. The results showed the average survival time of 187 patients were 38.4 months. 97 patients showed response to neoadjuvant chemotherapy. The GSTP1 Val and ERCC2 A/A genotypes had significantly higher rates of response to chemotherapy, with adjusted OR (95% CI) of 2.19 (1.15-6.21) and 2.88 (1.14-13.25). Individuals with ERCC2 A/A genotype were likely to have a lower risk of death from oseosarcoma, and the adjusted HR was 0.32 (0.13-0.95). Our study indicated test of GSTP1 and ERCC2 Lys751Gln polymorphisms might be a candidate pharmacogenomic factors to be explored in the future to identify the osteosarcoma patients who might benefit from chemotherapy.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7639-7644
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• 2014

Background: Results from previous studies concerning the association of ERCC4 rs1800067 polymorphism with risk of cancer were inconsistent. To explore the exact relation with susceptibility, we conducted the present meta-analysis. Materials and Methods: Literature of electronic databases including PubMed, Web of Science, EMBASE, Wanfang and Chinese National Knowledge Infrastructure (CNKI) were systematically searched. ORs and their 95%CIs were used to assess the strength of associations between ERCC4 polymorphism and cancer risk. Results: There was no significant association between ERCC4 rs1800067 AA or AG genotypes and overall risk of cancer (AA vs. GG: OR=0.998, 95%CI=0.670-1.486, P=0.992; AG vs. GG: OR=0.970, 95%CI=0.888-1.061, P=0.508). A dominant genetic model also did not demonstrate significant association of (AA+AG) genotype carriers with altered risk of overall cancer (OR=0.985, 95%CI=0.909-1.068, P=0.719). In addition, no significant association was observed between A allele of ERCC4 rs1800067 A/G polymorphism and altered cancer risk compared with G allele (OR=0.952, 95%CI=0.851-1.063, P=0.381). Subgroup analysis suggested that AA genotype carriers were significantly associated with decreased risk of glioma compared with wild-type GG genotype individuals (OR=0.523, 95%CI=0.275-0.993, P=0.048). For subgroup of lung cancer, A allele of ERCC4 rs1800067 A/G polymorphism was significantly associated with decreased risk of lung cancer compared with G allele (OR=0.806, 95%CI=0.697-0.931, P=0.003). Conclusions: This meta-analysis indicated that ERCC4 rs1800067 A/G polymorphism might not be associated with risk of overall cancer. However, individuals with the AA genotype were associated with significantly reduced risk of glioma compared with wild-type GG genotype; The A allele was associated with significantly reduced risk of lung cancer compared with G allele. Future large-scale studies performed in multiple populations are warranted to confirm our results.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.8
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• pp.4679-4683
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• 2013

Background: ERCC1 is considered as a promising molecular marker that may predict platinum based chemotherapy response in non small cell lung cancer patients. We therefore investigated whether its expression is indeed associated with clinical outcomes in advanced stage NSCLC patients. Materials and Methods: Pretreatment tumor biopsy samples of 83 stage 3B and 4 non-small cell lung cancer patients treated with platinum based chemotherapy were retrospectively analyzed for immunohistochemical ERCC1 expression. None of the patients received curative surgery or radiotherapy. Results: By calculating H- scores regarding the extent and intensity of immunohistochemical staining of tumor biopsy samples, ERCC1 expression was found to be positive in 50 patients (60.2%). ERCC1 positive and negative groups had no statistically significant differences regarding treatment response, progression free survival and overall survival (respectively p=0.161; p=0.412; p=0.823). Conclusions: In our study we found no association between ERCC1 expression and survival or treatment response. The study has some limitations, such as small sample size and retrospective analysis method. There is need of more knowledge for use of ERCC1 guided chemotherapy regimens in advanced stage NSCLC.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.449-452
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• 2013

Polymorphisms in DNA repair genes have been shown to influence DNA repair processes and to modify cancer susceptibility. Here we conducted a case-control study to assess the role of potential SNPs of DNA repair genes on the risk of glioma and meningioma. We included 297 cases and 458 cancer-free controls. Genotyping of XRCC1 Gln399Arg, XRCC1 Arg194Trp, XRCC2 Arg188His, XRCC3 Thr241Met, XRCC4 Ala247Ser, ERCC1 Asn118Asp, ERCC2 Lys751Gln and ERCC5 Asp1558His were performed in a 384-well plate format on the Sequenom MassARRAY platform. XRCC1 Arg194Trp (rs1799782) and ERCC2 Asp312Asn rs1799793 did not follow the HWE in control group, and genotype distributions of XRCC1 Gln399Arg rs25487, XRCC2 Arg188His rs3218536 and ERCC2 Asp312Asn rs1799793 were significantly different between cases and controls (P<0.05). We found XRCC1 399G/G, XRCC1 194 T/T and XRCC3 241T/T were associated with a higher risk when compared with the wild-type genotype. For ERCC5 Asp1558His, we found G/G genotype was associated with elevated susceptibility. In conclusion, our study has shown that XRCC1 Gln399Arg, XRCC1 Arg194Trp, XRCC3 Thr241Met and ERCC5 Asp1558His are associated with risk of gliomas and meningiomas. This finding could be useful in identifying the susceptibility genes for these cancers.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5507-5512
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• 2013

Objective: To investigate the correlation between ERCC1 expression levels in tumor tissue and peripheral blood lymphocytes (PBL) from patients with gastric cancer and assess the relationship between PBL DNA repair rate (DRR) and the efficacy of platinum chemotherapy. Methods: A total of 53 patients with gastric cancer receiving surgery and 20 controls were studied. ERCC1 protein expression in tumour tissue and PBL were determined by immunohistochemical staining. The PBL DRRs of 47 advanced patients and 20 controls were estimated by comet assay. Results: The positive expression rates of ERCC1 were 67. 9%, 56. 6% and 10.0% in tumour tissues, PBLs of gastric cancer patients, and PBLs of the control group. PBL ERCC1 expression correlated with that in tissue (${\chi}^2$=15. 463, p=0.000). Pearson contingency coefficient=0.475). DRRs of cancer patients by tail length (TL) (Z=4. 662, p=0.000) and tail moment (TM) (Z=3. 827, p=0.000) were significantly lower than that of control group. When TL was applied as an indicator, the correlation between DRR and chemotherapy efficacy was significant (Spearman rank correlation r=0.327, p=0.032). Patients with low levels of DRR in PBL presented better short-term efficacy of chemotherapy than those with high levels of DRR. Conclusions: The ERCC1 expression in PBLs may indirectly reflect ERCC1 expression in gastric cancer tissues. Compared with non-cancer populations, patients with gastric cancer may have lower DNA repair capacity. DRR in PBL may predict the short-term efficacy of platinum-based chemotherapy for patients with advanced gastric cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1505-1510
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• 2012

To aim of this was to observe emodin-mediated cytotoxicity and its influence on Rad51 and ERCC1 expressionin non-small cell lung cancer (NSCLC). NSCLC cells were cultured in vitro with emodin at various concentrations (0, 25, 50, 75 and $100\;{\mu}mol/L$) for 48h and the proliferation inhibition rate was determined by the MTT method. Then, NSCLC were treated with emodin (SK-MES-1 $40\;{\mu}mol/L$, A549 $70\;{\mu}mol/L$) or $20\;{\mu}mol/L$ U0126 (an ERK inhibitor) for 48 h, or with various concentrations of emodin for 48 h and the protein and mRNA expressions of ERCC1 and Rad51 were determined by RT-PCR and Western blot assay, respectively. Emodin exerted a suppressive effect on the proliferation of NSCLC in a concentration dependent manner. Protein and mRNA expression of ERCC1 and Rad51 was also significantly decreased with the dose. Vacuolar degeneration was observed in A549 and SK-MES-1 cell lines after emodin treatment by transmission electron microscopy. Emodin may thus inhibited cell proliferation in NSCLC cells by downregulation ERCC1 and Rad51.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3457-3461
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• 2015

Background: Previous studies have suggested that Morinda citrifolia (Noni) has potential to reduce cancer risk. Objective: The purpose of this study was to investigate the effect of Noni, cisplatin, and their combination on DNA repair genes in the SiHa cervical cancer cell line. Materials and Methods: SiHa cells were cultured and treated with 10% Noni, $10{\mu}g/dl$ cisplatin or their combination for 24 hours. Post culturing, the cells were pelleted, RNA extracted, and processed for investigating DNA repair genes by real time PCR. Results: The expression of nucleotide excision repair genes ERCC1, ERCC2, and ERCC4 and base excision repair gene XRCC1 was increased 4 fold, 8.9 fold, 4 fold, and 5.5 fold, respectively, on treatment with Noni as compared to untreated controls (p<0.05). In contrast, expression was found to be decreased 22 fold, 13 fold, 16 fold, and 23 fold on treatment with cisplatin (p<0.05). However, the combination of Noni and cisplatin led to an increase of 2 fold, 1.6 fold, 3 fold, 1.2 fold, respectively (p<0.05). Conclusions: Noni enhanced the expression of DNA repair genes by itself and in combination with cisplatin. However, high expression of DNA repair genes at mRNA level only signifies efficient DNA transcription of the above mentioned genes; further investigations are needed to evaluate the DNA repair protein expression.