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

Cancer Biology & Medicine

关键词: gastric cancer;    polymorphism;    oxaliplatin;    chemotherapy;    ERCC1;    XPD;    XPG;    XRCC1.;   

DOI  :  10.1007/s11805-009-0328-z

来源: DOAJ

【 摘 要 】

OBJECTIVE To investigate whether polymorphisms in ERC1, XPD, XPG, XRCC1 genes are associated with clinical outcomes in advanced gastric cancer (AGC) patients treated with oxaliplatin-based chemotherapy. METHODS The genetic polymorphisms in ERCC1, 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.RESULTSThe 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 signi fi cantly 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). CONCLUSIONTesting 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.

【 授权许可】

Unknown