ERCC1 single nucleotide polymorphism C8092A, but not its expression is associated with survival of esophageal squamous cell carcinoma patients from Fujian province, China

• Published in: PloS one 2014-09, Vol.9 (9), p.e106600
• Main Authors: Chen, Wan-Hua, Xin, Pei-Ling, Pan, Qun-Xiong, Chen, Ya-Yun, Wang, Cong-Ren, Zhang, Zhi-Shan, Chen, Yi-Feng, Zhang, Chao-Yang, Cai, Wen-Jie
• Format: Article
• Language: English
• Subjects: Aged; Alleles; Biology and Life Sciences; Biopsy; Cancer therapies; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - mortality; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - therapy; Cell Survival; Cell Transformation, Neoplastic - genetics; Chemotherapy; Chemotherapy, Adjuvant; China; Cisplatin; Clinical outcomes; Colorectal cancer; Consent; DNA Mutational Analysis; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Endonucleases - genetics; Endonucleases - metabolism; ERCC1 protein; Esophageal cancer; Esophageal carcinoma; Esophageal Neoplasms - genetics; Esophageal Neoplasms - mortality; Esophageal Neoplasms - pathology; Esophageal Neoplasms - therapy; Esophageal Squamous Cell Carcinoma; Esophagus; Female; Gene Expression; Genotype; Genotyping; Hospitals; Humans; Laboratories; Lung cancer; Lymph Nodes - metabolism; Lymph Nodes - pathology; Male; Medical prognosis; Medicine and Health Sciences; Middle Aged; Neoplasm Grading; Neoplasm Staging; Nuclei; Nuclei (cytology); Oncology; Patients; Platinum; Polymorphism; Polymorphism, Single Nucleotide; Prognosis; Protein expression; Proteins; Radiation therapy; Radiotherapy, Adjuvant; Repair; Single-nucleotide polymorphism; Squamous cell carcinoma; Studies; Surgery; Survival; Systematic review; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0106600

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.