ERCC1 polymorphism, expression and clinical outcome of oxaliplatin-based adjuvant chemotherapy in gastric cancer

Abstract

in gastric cancer patients treated with oxaliplatin-based adjuvant chemotherapy (P < 0.05).CONCLUSION: ERCC1 codon 118 polymorphism has no significant impact on ERCC1 mRNA expression, and the intratumoral ERCC1 mRNA level but not codon 118 polymorphism may be a useful predictive parameter for the relapse and survival of gastric cancer patients receiving oxaliplatin-based adjuvant chemotherapy. INTRODUCTIONIn China, gastric cancer is the leading cause of cancer deaths, accounting for nearly one-fourth of all cancer deaths. Surgery is the primary modality for managing early-stage and locally-advanced disease. However, even after gastrectomy, the majority of patients develop local or distant recurrence [1] . Adjuvant chemotherapy for gastric cancer has been under clinical investigation for more than four decades. Fluoropyrimidines, platinumdrugs and taxanes were shown to be effective in the treatment of gastric cancer. However, the response rates of these drugs or their combinations were less than 50% [2,3] . There is no standard regimen for postoperative treatment at the moment. Having an effective assay to predict the response to a given chemotherapeutic protocol beforehand would greatly enhance the success rate as well as the life quality of the patients.The nucleotide excision repair (NER) system plays a significant role in repairing a variety of distorting Abstract AIM: To determine the influence of excision repair cross complementing group 1 (ERCC1 ) codon 118 polymorphism and mRNA level on the clinical outcome of gastric cancer patients treated with oxaliplatin-based adjuvant chemotherapy. METHODS: Eighty-nine gastric cancer patients treated with oxalipatin-based adjuvant chemotherapy were included in this study. ERCC1 codon 118 C/T polymorphism was tested by polymerase chain reaction-ligation detection reaction (PCR-LDR) method in peripheral blood lymphocytes of those patients; and the intratumoral ERCC1 mRNA expression was measured using reverse transcription PCR in 62 patients whose tumor tissue specimens were available. RESULTS: No significant relationship was found between ERCC1 codon 118 polymorphism and ERCC1 mRNA level. The median relapse-free and overall survival period was 20.1 mo and 28.4 mo, respectively. The relapse-free and overall survivals in patients with low levels of ERCC1 mRNA were significantly longer than those in patients with high levels (P < 0.05), while there was no significant association found between ERCC1 118 genotypes and the disease prognosis. Multivariate analysis also showed that ERCC1 mRNA level was a potential predictor for relapse and survival

Bax Predicts Outcome in Gastric Cancer Patients Treated with 5-fluorouracil, Leucovorin, and Oxaliplatin Palliative Chemotherapy

“…Several studies have shown that expression of TS and ERCC1 has predictive value of response to chemotherapy and survival in advanced gastric cancer patients receiving systemic chemotherapy with 5-FU and platinum-based regimens [22][23][24][28][29][30][31]. Recently, Kwon et al reported a significant correlation between high expression of ERCC1 and poor survival in 64 advanced gastric cancer patients treated with FOLFOX using immunohistochemical staining [29].…”

A randomized phase III study of adjuvant platinum/docetaxel chemotherapy with or without radiation therapy in patients with gastric cancer

“…Hence, among a variety of potentially relevant molecules, ERCC1 and MAP-Tau were selected because they are involved in the process of 'recovery' from the platinum and taxane cytotoxic eVect, respectively [28][29][30]. Moreover, the expression of tyrosine kinase receptors (TKRs), such as HER2, EGFR and MET, has being thoroughly investigated [31][32][33] in solid tumors, but Wndings in gastric cancer are still controversial.…”

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

“…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). However, the results are conflicting.…”