Investigation of ERCC1 and ERCC2 gene polymorphisms and response to chemotherapy and overall survival in osteosarcoma

Q, Zhang; Ly, Lv; Bj, Li; Zhang, J; Fang, Wei

doi:10.4238/2015.september.22.17

Cited by 19 publications

(16 citation statements)

References 18 publications

(19 reference statements)

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“…Then the remaining 76 articles were estimated for eligibility according to our inclusion and exclusion criteria. Finally six eligible articles [12–14, 17, 20, 21] were included in our meta-analysis. The flow diagram of study selection process and reasons for exclusion was represented in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Cancer cells overexpressing ERCC1 were correlated with drug resistance to chemotherapy containing cisplatin, carboplatin, or oxaliplatin in several types of tumors such as gastric, bladder, ovarian, colorectal, and lung carcinomas [28]. Zhang et al observed that the ERCC1 rs11615 polymorphism might influence the clinical outcomes and response to chemotherapy for patients with OS, and patients with CC genotype in ERCC1 rs11615 polymorphism had better response to chemotherapy [20] which was also confirmed in our meta-analysis, we furthermore incorporated all relevant data together and considered OS patients with CC or TC + CC genotypes had better response to chemotherapy. Thus, the genetic polymorphism of rs11615 is a potentially alternative target for OS patients in clinical diagnosis, and the C allele in ERCC1 rs11615 polymorphism for patients with OS could be an underlying candidate predictor in clinical chemotherapy treatment.…”

Section: Discussionmentioning

confidence: 99%

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Genetic polymorphisms in ERCC1 and ERCC2 genes are associated with response to chemotherapy in osteosarcoma patients among Chinese population: a meta-analysis

Zhang

Hong

et al. 2017

World J Surg Onc

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BackgroundThere existed controversies about the association between the response to chemotherapy for osteosarcoma (OS) patients and the genetic polymorphisms in excision repair cross-complementation group (ERCC1 and ERCC2) genes. We aimed to perform a meta-analysis to comprehensively evaluate the association.MethodWe searched multiple databases for literature retrieval including the PubMED (1966 ∼ 2017), Embase (1980 ∼ 2017), and the Web of science (1945 ∼ 2017). The overall odds ratios(OR) and their corresponding 95% confidence interval (CI) were calculated for the three polymorphisms under the dominant, recessive, and allelic models.ResultsFrom six eligible articles in our study, we found that for ERCC1 rs11615 polymorphism, a significant association was detected between the chemotherapy response and the polymorphism under all three models (dominant model: OR = 2.015, P = 0.005; recessive model: OR = 1.791, P = 0.003; allelic model: OR = 1.677, P = 0.003), and OS patients carrying C allele in rs11615 polymorphism were more likely to response to chemotherapy. In terms of ERCC2 rs1799793 polymorphism, this polymorphism was significantly associated with the response to chemotherapy for OS patients under recessive model (OR = 1.337, P = 0.036), and patients with AG + AA genotype in rs1799793 polymorphism were more appropriate to receive chemotherapy. With respect to ERCC2 rs13181 polymorphism, this polymorphism was not correlated with the response to chemotherapy for OS patients under all three models.ConclusionsOur meta-analysis suggested that among Chinese population, the rs11615 and rs1799793 polymorphisms were significantly correlated with the response to chemotherapy for patients with OS, and patients with CC or TC + CC genotypes in ERCC1 rs11615 polymorphism or AG + AA genotype in ERCC2 rs1799793 polymorphism were more suitable for chemotherapy.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Genetic polymorphisms in ERCC1 and ERCC2 genes are associated with response to chemotherapy in osteosarcoma patients among Chinese population: a meta-analysis

Zhang

Hong

et al. 2017

World J Surg Onc

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“…The positive association between this variant and better OS rate in patient with osteosarcoma was previously reported. However, the association with EFS rate was not clearly investigated [ 17 , 21 – 25 ].…”

Section: Discussionmentioning

confidence: 99%

The effect of ERCC1 and ERCC2 gene polymorphysims on response to cisplatin based therapy in osteosarcoma patients

et al. 2018

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BackgroundCisplatin is one of the major drugs that used in the treatment of osteosarcoma. Cisplatin exerts its function by making cisplatin-DNA adducts culminating in cellular death. These adducts found to be repaired by nucleotide excision repair (NER) pathway. This study aimed to evaluate if polymorphisms in two main genes in the NER pathway, excision repair cross-complementing group 1 and 2 (ERCC1 and ERCC2) could affect the histological response to cisplatin based chemotherapy or clinical outcomes, particularly, event free survival (EFS) and overall survival (OS) rates.MethodERCC1 (C118T (rs11615) and C8092A (rs3212986)) and ERCC2 (A751C (rs171140) and G312A (rs1799793)) polymorphisms were analysed in 44 patients with osteosarcoma, who were treated with cisplatin based neoadjuvant chemotherapy. DNA was extracted from patient’s formalin-fixed paraffin-embedded (FFPE) samples, patient’s genotypes were determined by using polymerase chain reaction-restriction fragment length polymorphism PCR-RFLP assay. The distribution of the patients’ genotype and the allele frequencies were reported. The association between each of these genotypes and many clinical and patho-histological parameters (e.g. EFS, OS and patho-histological response to treatment) was examined. The associations between gender, tumor location, presence of metastasis at diagnosis, histological subtypes, and type of neoadjuvant chemotherapy and between the histological response, EFS and OS rates were also examined.ResultsThis study revealed that there was a positive and significant association between ERCC1 C8092 A genotypes and median EFS rate in years; patients who were carriers of C allele (CC & CA) were found to have longer EFS rates than patients with AA genotype (P value = 0.006) and the median EFS rates were respectively as following: 2.04, 0.24 years. As well, both the presence of metastasis and the histological subtype at the time of diagnosis, were able to affect the EFS rate but not the OS. However, there was a positive correlation between OS rate and the patients’ primary response to treatment.ConclusionsOur results suggested that ERCC1 8092 C allele may play a role as a candidate prognostic marker in patients with osteosarcoma.Electronic supplementary materialThe online version of this article (10.1186/s12881-018-0627-4) contains supplementary material, which is available to authorized users.

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“…Expression of proteins including CHEK1, CHEK2, ERCC1, ERCC2, PARP and WEE1 predispose cancer cells treated with chemotherapy toward DNA repair and proliferation. As such, these proteins have been identified as either prognostic biomarkers or therapeutic targets to improve chemotherapeutic effects in pediatric tumors [122][123][124][125][126][127][128][129][130][131][132] . The mechanisms that balance the expression and stability of these proteins continue to be areas of active investigation.…”

Section: Dna Damage Pathwaysmentioning

confidence: 99%

Dodging the bullet: therapeutic resistance mechanisms in pediatric cancers

Shah¹

2019

CDR

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While advances in the treatment of pediatric cancers have improved survival to > 80% across all tumor types, drug resistance continues to limit survival for a considerable number of patients. We review the known mechanisms of resistance in pediatric cancers, including processes that impair conventional chemotherapies, newer classes of targeted small molecule antineoplastic drugs, and monoclonal antibodies. We highlight similarities and differences in treatment approach and resistance between pediatric and adult cancers. We also discuss newer areas of research into drug resistance, including extracellular and immune factors.

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Investigation of ERCC1 and ERCC2 gene polymorphisms and response to chemotherapy and overall survival in osteosarcoma

Cited by 19 publications

References 18 publications

Genetic polymorphisms in ERCC1 and ERCC2 genes are associated with response to chemotherapy in osteosarcoma patients among Chinese population: a meta-analysis

Genetic polymorphisms in ERCC1 and ERCC2 genes are associated with response to chemotherapy in osteosarcoma patients among Chinese population: a meta-analysis

The effect of ERCC1 and ERCC2 gene polymorphysims on response to cisplatin based therapy in osteosarcoma patients

Dodging the bullet: therapeutic resistance mechanisms in pediatric cancers

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