ERCC1 Single Nucleotide Polymorphism C8092A, but Not Its Expression Is Associated with Survival of Esophageal Squamous Cell Carcinoma Patients from Fujian Province, China

Abstract

Esophageal carcinoma is one of the world's deadliest cancers. Esophageal squamous cell carcinoma (ESCC) is more frequent than adenocarcenoma (AC) in China. Platinum-based chemotherapy with surgical resection is a common treatment approach for ESCC; however, the treatment response is uncertain. Evidence suggests polymorphisms in genes encoding excision repair cross-complementing group 1 (ERCC1), a protein involved in nuclear excision repair (NER), may help predict response to cisplatin and other platinum-based chemotherapeutics. Multiple ERCC1 single nucleotide polymorphisms (SNPs) have been associated with platinum chemotherapy response. Two common SNPs occur at the C8092A and C118T loci. Our study aimed to determine if 1) an association exists between ERCC1 tumor expression and patient survival, 2) whether adjuvant therapy influence on survival is related to histological ERCC1 presence in tumor cell nuclei, and 3) whether other clinicopathological characteristics in a cohort of patients following surgery for various stages of ESCC are associated with tumor ERCC1 expression. One hundred eight patients were included in the study, and tumor biopsy was collected for genotyping and immunohistochemical analysis of ERCC1. Sixty-seven patients (62%) received no adjuvant therapy, and the rest had either platinum-based chemotherapy (28.5%), radiotherapy (6.5%) or both treatments (2.8%). Log-rank analysis revealed no significant connection between tumor ERCC1 expression (P = 0.12) or adjuvant therapy (P = 0.56) on patient survival. Also, non-parametric Mann-Whitney analysis showed no significant link between tumor size or nodus tumor formation and ERCC1 presence in patients in the study. Interestingly, C8092A SNP showed significant association with patient survival (P = 0.01), with patients homozygous for the mutant allele showing the most significantly reduced survival (P = 0.04) compared to those homozygous for the dominant allele (CC). Our results provide novel insight into the genotypic variation of patients from Quanzhou, Fujian province China.

Clinical significance of tumor cells in the peripheral blood of patients with esophageal squamous cell carcinoma

“…Late treatment leads to a poor prognosis, with 5-year survival rates of only 15% to 25%. [1–3] A poor prognosis is usually due to recurrence and metastasis.…”

Correlation analysis between polymorphism of GSTP1, XPD and XRCC1 gene in esophageal carcinoma patients and treatment efficiency of cisplatin chemo-therapy

“…Therefore, identification of molecular index predicting drug sensitivity may help to guide the application of EC. Polymorphism of Excision Repair Cross-Complementing 1 (ERCC1) gene is correlated with treatment efficacy using platinum drug in EC patients [21]. However, few studies have been performed regarding the correlation between XRCC1, XPD and GSTP1 gene and platinum drug efficacy against EC.…”

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

“…Many epidemiologic studies have reported that ERCC1 polymorphisms may influence the outcome of cisplatin treatment in gastric cancer, non-small cell lung cancer (NSCLC), ovarian cancer, and esophageal squamous cell carcinoma (Qi et al, 2013;Chen et al, 2014;Gao et al, 2014;Liu et al, 2014). Liu et al (2014) conducted a cohort study to investigate the role of ERCC1 gene polymorphism in response to chemotherapy and clinical outcome in gastric cancer, and did not find the ERCC1 rs3212986 polymorphism to be associated with OS in gastric cancer.…”

“…Gao et al (2014) also conducted a cohort study to investigate the role of three SNPs of ERCC1 in the clinical outcome of NSCLC, and found that the TT genotype of ERCC1 rs11615 and the AA genotype of rs3212986 polymorphisms were associated with increased risk of death from NSCLC. Chen et al (2014) showed that the ERCC1 rs3212986 polymorphism showed a significant association with survival in epithelial ovarian cancer patients. However, another study found that ERCC1 rs3212986 did not produce a significant difference in the response to chemotherapy or overall survival in ovarian cancer (Qi et al, 2013).…”