The role of single nucleotide polymorphisms of the ERCC1 and MMS19 genes in predicting platinum-sensitivity, progression-free and overall survival in advanced epithelial ovarian cancer

ABSTRACT. This study aims to investigate the association between ERCC1 codon C118T polymorphism and the response rate of platinumbased chemotherapy in patients with late-stage bladder cancer. A total of 41 eligible patients histologically confirmed as having stage IV muscleinvasive transitional cell carcinoma of the bladder were treated with platinum-based chemotherapy for 2-6 cycles. The genotypes of patients were determined by PCR amplification of genomic DNA followed by restriction enzyme digestion. Positive responses were categorized as complete and partial responses. In addition, progression-free survival (PFS) and overall survival (OS) were also determined as indicators of long-term outcomes. The genotype frequencies of C/C, C/T and T/T genotypes were 56.1, 34.1, and 9.8%, respectively. Positive response was observed in 14 patients (34.1%), while 27 patients (65.9%) were negative responders. As compared with individuals carrying the C/T and T/T genotypes, those with the C/C genotype had significantly improved short-term treatment responses (P = 0.018). The median PFS of patients carrying the C/C genotype was 6.3 months, while that of patients with C/T and T/T genotypes was 4.2 months (P = 0.023). Moreover, the median OS for patients carrying the C/C genotype was also longer as compared with that of patients carrying C/T and T/T (11.7 months vs 8.5 months, P = 0.040). Our results indicated that the ERCC1 codon 118 polymorphism may have predictive potential for chemotherapy treatment responses in late-stage bladder cancer patients.

Section: Discussionmentioning

confidence: 80%

ERCC1 C118T polymorphism has predictive value for platinum-based chemotherapy in patients with late-stage bladder cancer

Cai

et al. 2016

“…However, some patients do not appear to benefit from concurrent chemoradiotherapy, and thus, more individualized treatment options are needed. To date, a number of studies have reported correlation between ERCC1 expression and PFS and OS after platinumbased therapy in several cancers including colorectal, non-small cell lung, and ovarian tumors (Jiang et al, 2012;Li et al, 2013;Moxley et al, 2013). However, only a few studies have investigated such correlations in nasopharyngeal carcinoma, with inconsistent results.…”

Section: Discussionmentioning

confidence: 99%

Correlation between ERCC1 expression and concurrent chemotherapy and radiotherapy in patients with locally advanced nasopharyngeal cancer

Liang

Lin

et al. 2015

ABSTRACT. In this study, the expression of DNA excision repair cross-complementing gene 1 (ERCC1) in local advanced nasopharyngeal carcinoma has been correlated with the efficacy of concurrent chemoradiotherapy. A total of 76 patients diagnosed with undifferentiated nasopharyngeal carcinoma diagnosed by nasopharyngeal biopsy and undergoing single-agent cisplatin chemotherapy (80 mg/m 2 ) with concurrent radiotherapy (on the first, twenty-second, and forty-third day, 5 times per week, mean dose 74 Gy, range 70-78 Gy) at the Affiliated Cancer Hospital of Guangxi Medical University between January and December 2010 were included. After chemoradiotherapy, outcomes and long-term survival were evaluated. Immunohistochemistry was used to detect expression of ERCC1 protein in nasopharyngeal carcinoma. The relationship between the expression of ERCC1 and efficacy of concurrent chemoradiotherapy and long-term survival were analyzed. ERCC1 was expressed in 42.1% of cases. The expression of ERCC1 was correlated with T 5804-5811 (2015) stage and clinical staging (P < 0.05), but not with gender, age, or N stage. The response rate in the ERCC1-positive and ERCC1-negative groups was 75.0% and 97.7%, respectively (P < 0.05). In the 72 cases with follow-up available, 1-, 2-, and 3-year survival rates were 91.0, 83.3, and 79.0%; they were 92.4, 87.8, 80.5%, respectively, in the ERCC1-positive group, and 87.9, 77.4, 77.4%, respectively, in the ERCC1-negative group. The expression of ERCC1 may be a sensitive prognostic indicator of concurrent chemoradiotherapy in locally advanced nasopharyngeal carcinoma.

“…Polymorphisms in ERCC1 genes are reported to be a potential predictor for the response to chemotherapy and clinical outcome of cancer patients, such nasopharyngeal carcinoma, colorectal cancer, and non-small cell lung as well as ovarian cancer (Chen et al, 2013;Moxley et al, 2013;Oguri et al, 2013;Tiseo et al, 2013). For gastric cancer, 2 systemic reviews indicated that ERCC1 rs11615C>T polymorphisms are useful prognostic factors in gastric cancer treated with platinum-based chemotherapy (Liu et al, 2011;Wang et al, 2012 Table 3.…”

Section: Discussionmentioning

confidence: 99%

“…ERCC1 is located on chromosome 19q13.32, interacts with other NER proteins, and guides the 5'-incision activity of the NER pathway (Volker et al, 2001). Previous studies reported that the ERCC1 polymorphism is correlated with increased chemotherapeutic sensitivity and may be a prognostic marker for various cancers treated with chemotherapy (Mlak et al, 2013;Moxley et al, 2013;Rumiato et al, 2013). The association between the ERCC1 polymorphism and gastric cancer has been reported in several studies (Huang et al, 2008;Liang et al, 2010;Yin et al, 2011).…”

Section: Introductionmentioning

confidence: 96%

Study on the ERCC1 gene polymorphism response to chemotherapy and prognosis of gastric cancer

Liu

Jin

et al. 2014

ABSTRACT. We conducted a cohort study to investigate the role of 2 single-nucleotide polymorphisms of the excision repair crosscomplimentary group 1 (ERCC1) gene polymorphism in response to chemotherapy and clinical outcomes of gastric cancer. A total of 231 patients with newly diagnosed and histopathologically confirmed primary gastric cancer participated in the study. ERCC1 rs11615 and rs3212986 were genotyped. Individuals with the ERCC1 rs11615 TT genotype and the T allele showed a significant poorer response to chemotherapy compared to the wild-type genotype. Patients carrying the rs11615 TT genotype (22.8 months) and the T allele (24.2 months) showed a significantly shorter median survival time when compared with the GG genotype (33.7 months). Cox proportional hazard regression analysis showed that adjusted hazard ratios of overall survival in those carrying the rs11615 TT genotype and the T allele were 2.79 (1.15-7.26) 8723©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 13 (4): 8722-8728 (2014) ERCC1 polymorphism and prognosis of gastric cancer and 1.84 (1.19-2.87) when using the wild-type genotype as a reference variable. In conclusion, this study reports that the ERCC1 rs11615 TT polymorphism can be used as a prognostic marker to determine the clinical outcome of gastric cancer patients treated with 5-fluorouracilbased chemotherapy.