Polymorphisms of ERCC1, XPD, XRCC1 and XPG Predict Clinical Outcome in Advanced Gastric Cancer Patients Receiving Oxaliplatin-Based Chemotherapy in Chinese Population

OBJECTIVE To investigate whether polymorphisms in ERCC1, XPD, XPG, XRCC1 genes are associated with clinical outcomes in advanced gastric cancer （AGC） patients treated with oxaliplatinbased chemotherapy. METHODS The genetic polymorphisms in ERCCI, XPD, XPG, XRCC1 were determined in 94 advanced gastric cancer patients treated with oxaliplatin-based chemotherapy, using TaqMan-MGB probes. The clinical response of 60 patients with stage IV disease, time to progression （TTP） and overall survival （OS） of 94 patients were evaluated. RESULTS The overall disease control rate （CR ＋ PR ＋ SD） of the 60 patients in stage IV was 70% （42/60）. Patients with XRCC1 399 G/G, XPG 46 C/C genotypes showed enhanced response to the oxaliplatin-based chemotherapy compared to those with other genotypes （P 〈 0.05）. The median OS and TTP of the patients were 5.5 months and 9.0 months, respectively. Among the 4 types of polymorphisms in the study, XRCC1 399 G/A ＋ A/A, XPG 46 C/T ＋ T/T genotypes were regarded to be associated with chemoresistance and poor survival （P 〈 0.05）. Combination analysis of the 2 polymorphisms using the Kaplan-Meier method revealed that the TTP and OS of the patients with a number of risk genotypes were significantly shortened （P 〈 0.05）. No significant association was found between the genotypes of the XPD codon 751, the ERCC1 codon 118 and the clinical outcome （P 〉 0.05）. CONCLUSION Testing for XRCC1 399, XPG 46 polymorphisms may allow identification of the gastric cancer patients who will benefit from oxaliplatin-based chemotherapy. Specific polymorphisms may influence clinical outcomes of AGC patients. Selecting specific chemotherapy based on pretreatment genotyping represents an innovative strategy that warrants prospective studies.

ERCC1 Asn118Asn polymorphism as predictor for cancer response to oxaliplatin-based chemotherapy in patients with advanced colorectal cancer

Objective： To assess whether the polymorphism of ERCC1 Asn118Asn （C → T） had effects on cancer response to chemotherapy and outcome in Chinese patients treated with oxaliplatin as first-line chemotherapy regimen for advanced colorectal cancer. Methods： ERCC1 Asn 118Asn polymorphism was analyzed in 99 patients with stages Ⅲ and Ⅳ advanced colorectal cancer treated with oxaliplatin-based chemotherapy, For all of the patients, ERCC1 Asnl18Asn genotype was analyzed for associations with treatment response and time to disease progress （TTP）. Results： The allele frequencies of the ERCC1 gene codon 118 were C/C 50.51% （50/99）, C/T 41.41% （41/99）, T/T 8.08% （8/99）, respectively. Patients with C/C genotype showed higher response rate than those with C/T ＋ T/T （OR = 3.764, 95% CI： 1.310-10.813）. The median TTP of all patients was 7 months （95% CI： 5.569--8.431）. Patients with C/C genotype showed a median TTP of 10 months （95% CI： 8.924-11.076）, which was longer than 5 months （95% CI： 4.424-5.576） in patients with C/T ＋ T/T genotypes. Conclusion： Our results showed a link between ERCC1 Asn118Asn genetic polymorphism and cancer response to oxaliplatin-based chemotherapy and time to disease progress in Chinese patients with advanced colorectal cancer. ERCC1 Asn 118Asn genotyping may be of predictive benefit in selecting treatment regimen for advanced colorectal cancer.