PTGs2/COX2 gene polymorphism associated with prognosis for patients with advanced colorectal cancer treated with capecitabine and oxaliplatin chemotherapy

Abstract

Background: Apoptosis is known to be a main pathway of chemotherapeutic agents-induced tumor cell death. Accordingly, the present study analyzed the impact of polymorphisms of apoptosis-related genes on outcome for patients with advanced colorectal cancer treated with capecitbine-oxaliplatin (XELOX) combination chemotherapy. Methods: Seventy-six patients with recurred or metastatic colorectal cancer treated with XELOX regimen were enrolled in the present study. The genomic DNA was extracted from paraffin-embedded tissue and single nucleotide polymorphisms (SNPs) of 16 apoptosis-related genes (TP53, BCL2, BCL2L [BCL2 ligand], TNFRSF10B, TNFSF10, AKT1, PTGS2/COX2, BID, RIPK1, FAS, FASL [FAS ligand], and caspase 3, 6-10) determined using a PCR-RFLP assay. Results: No significant association between SNPs and response was found for any genes analyzed. However, the TT genotype of PTGS2 (rs5275) was significantly correlated with a better progression-free survival (PFS) and overall survival (OS) compared to the combined T/C and C/C genotype (Hazard ratio [HR] = 0.47; 95% Confidential Interval [CI] = 0.22-0.99; p value = 0.046 and HR = 0.16; 95% CI = 0.04-0.65; p = 0.010, respectively) in a multivariate analysis adjusted to age ((pounds)60 vs. >60), disease status (metastatic vs. recurrent), and curative resection. Meanwhile, no association was noted between other polymorphisms and survival. Conclusion: SNP of PTGS2/COX2 gene was found to be correlated with PFS and OS in patients with advanced colorectal cancer treated with XELOX. However, further study is warranted to clarify the role of apoptosis-related genes as a prognostic biomarker in colorectal cancer patients treated with chemotherapy.