Search

Background: Patients with lung cancer (LC) have a poor quality of life (QoL) and easily suffer from psychological diseases. Previous studies focused less on the relationship between genetic factors and QoL, depression, and anxiety status in LC patients. The current study is intended to explore the relationship between SNPs and haplotypes of ERCC1 and ERCC2 and the QoL, depression and anxiety status of patients with LC.Methods: QoL, depression and anxiety status were assessed in 291 LC patients using the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30), EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13), SDS and SAS. Nine tag SNPs of ERCC1 and ERCC2 were detected using an improved multiplex ligation detection reaction (iMLDR) technique. Haplotype analysis was conducted using the software Haploview 4.2. The association between SNPs or haplotypes and QoL or depression or anxiety in LC patients was analyzed by regression analysis.Results: ERCC1 rs11615 was associated with emotional functioning (P = 0.027), and ERCC1 rs3212986 was associated with anxiety scores (P = 0.018). ERCC1 rs762562-rs3212986 haplotype was associated with cognitive function (P = 0.029), somatic function (P = 0.014) and dysphagia (OR = 3.32, P = 0.044). Patients with ERCC1 rs3212986-rs11615 AG haplotype had worse cognitive function (adjusted Beta = - 5.42) and somatic function (adjusted Beta = - 6.55) and had severer symptoms of loss of appetite (adjusted OR = 1.67) and dysphagia (adjusted OR = 4.43) (All adjusted P < 0.05). ERCC2 rs13181-rs3916874-rs238416 haplotype was associated with emotional functioning (P = 0.035), pain at other sites (OR 1.88, P = 0.014), chest pain (OR 0.42, P = 0.02), dysphagia (OR 2.82, P = 0.048), and anxiety status (OR 0.23, P = 0.009).Conclusion: After adjustment for environmental factors, SNPs and haplotypes of ERCC1 and ERCC2 were associated with different domains of QoL, depression and anxiety in LC patients. [ABSTRACT FROM AUTHOR]

Background: Trichothiodystrophy (TTD) is a rare, autosomal recessive, multisystem disorder most commonly caused by variants in ERCC2.Case Presentation: Here, we describe the first Chinese patient with a novel variant in ERCC2. A male infant, who was born to a healthy non-consanguineous couple, exhibited brittle hair, hair loss ichthyosis, eczema, retinal pigmentation and hypospadias. He carried a novel heterozygous ERCC2 variant. The maternal variant (c.2191-18_2213del) is a previous described genomic deletion that affects the splicing of intron 22. The paternal variant (c.1666-1G > A), that occurs in the splice site of intron 17 and likely alters ERCC2 gene function through aberrant splicing, has not been reported previously.Conclusions: Our case reported a novel pathogenic variant in ERCC2, which expanded the known genetic variants associated with TTD. [ABSTRACT FROM AUTHOR]

Background: Single nucleotide polymorphisms (SNPs) in DNA repair genes have a potential clinical value in predicting treatment outcomes. In the current study, we examined the association of SNPs in the genes XRCC1-rs25487, ERCC1-rs11615, ERCC2-rs238406, and ERCC2-rs13181 with colorectal cancer (CRC) risk, relapse-free survival (RFS), overall survival (OS), and toxicity during chemotherapy.Methods: SNPs were analysed in 590 CRC cases and 300 controls using TaqMan technology. The association of SNPs with CRC risk and toxicity during chemotherapy was analysed using Chi2 test. The Kaplan-Meier method and log-rank test was used to measure the effects of the SNPs on RFS and OS.Results: The CC genotype of ERCC2-rs238406 and the ERCC2-rs13181 C allele were associated with a significantly increased risk of CRC. The ERCC1-rs11615 genotype T/T was associated with stomatitis in adjuvant chemotherapy (p = 0.03). Also, more patients with the ERCC2-rs13181 C allele needed dose reduction compared to patients with the A/A genotype (p = 0.02). In first line chemotherapy, more patients with the ERCC1-rs11615 C allele suffered from nausea compared to those with the T/T genotype (p = 0.04) and eye reactions and thrombocytopenia were more common in patients with the ERCC2-rs13181 C allele compared to the A/A genotype (p = 0.006 and p = 0.004, respectively). ERCC2- rs238406 C/C was also associated with a higher frequency of thrombocytopenia (p = 0.03). A shorter 5-year OS was detected in stage I & II CRC patients with the ERCC2- rs238406 C allele (p = 0.02). However, there was no significant association between the SNPs and 5-year RFS.Conclusions: Both SNPs in ERCC2 were associated with risk of CRC as well as toxicity during first line treatment. In addition, ERCC2- rs238406 was linked to OS in early stage CRC. The ERCC1-rs11615 variant was associated with toxicity during adjuvant chemotherapy. The results add support to previous findings that SNPs in ERCC1 and ERCC2 have a prognostic and predictive value in clinical management of CRC. [ABSTRACT FROM AUTHOR]

Background: There 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. Method: We 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. Results: From 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. Conclusions: Our 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. [ABSTRACT FROM AUTHOR]

Background: Deficient nucleotide excision repair (NER) activity causes a variety of autosomal recessive diseases including xeroderma pigmentosum (XP) a disorder which pre-disposes to skin cancer, and the severe multisystem condition known as Cockayne syndrome (CS). In view of the clinical overlap between NER-related disorders, as well as the existence of multiple phenotypes and the numerous genes involved, we developed a new diagnostic approach based on the enrichment of 16 NER-related genes by multiplex amplification coupled with next-generation sequencing (NGS).Methods: Our test cohort consisted of 11 DNA samples, all with known mutations and/or non pathogenic SNPs in two of the tested genes. We then used the same technique to analyse samples from a prospective cohort of 40 patients. Multiplex amplification and sequencing were performed using AmpliSeq protocol on the Ion Torrent PGM (Life Technologies).Results: We identified causative mutations in 17 out of the 40 patients (43%). Four patients showed biallelic mutations in the ERCC6(CSB) gene, five in the ERCC8(CSA) gene: most of them had classical CS features but some had very mild and incomplete phenotypes. A small cohort of 4 unrelated classic XP patients from the Basque country (Northern Spain) revealed a common splicing mutation in POLH (XP-variant), demonstrating a new founder effect in this population. Interestingly, our results also found ERCC2(XPD), ERCC3(XPB) or ERCC5(XPG) mutations in two cases of UV-sensitive syndrome and in two cases with mixed XP/CS phenotypes.Conclusions: Our study confirms that NGS is an efficient technique for the analysis of NER-related disorders on a molecular level. It is particularly useful for phenotypes with combined features or unusually mild symptoms. Targeted NGS used in conjunction with DNA repair functional tests and precise clinical evaluation permits rapid and cost-effective diagnosis in patients with NER-defects. [ABSTRACT FROM AUTHOR]

Background: The relationship between ERCC2 polymorphisms and the risk of radiotoxicity remains inconclusive. The aim of our study is to systematically evaluate the association between ERCC2 polymorphisms and the risk of radiotoxicity.Methods: Publications were identified through a search of the PubMed and Web of Science databases up to August 15, 2015. The pooled odds ratios (ORs) with corresponding 95 % confidence intervals (CIs) were calculated to evaluate the association between ERCC2 polymorphisms and radiotoxicity. Trial sequential analysis (TSA) and power calculation were performed to evaluate the type 1 and type 2 errors.Results: Eleven studies involving 2584 patients were ultimately included in this meta-analysis. Conventional meta-analysis identified a significant association between ERCC2 rs13181 polymorphism and radiotoxicity (OR = 0.71, 95 % CI: 0.55-0.93, P = 0.01), but this association failed to get the confirmation of TSA.Conclusions: The minor allele of rs13181 polymorphism may confer a protect effect against radiotoxicity. To confirm this correlation at the level of OR = 0.71, an overall information size of approximate 2800 patients were needed. [ABSTRACT FROM AUTHOR]

Background: There 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., Method: We 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., Results: From 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., Conclusions: Our 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.