Prostaglandin synthase 2/cyclooxygenase 2 (PTGS2/COX2) 8473T>C polymorphism associated with prognosis for patients with colorectal cancer treated with capecitabine and oxaliplatin

Cancer Chemother Pharmacol. 2009 Oct;64(5):953-60. doi: 10.1007/s00280-009-0947-3. Epub 2009 Feb 15.

Abstract

Purpose: The present study analyzed the polymorphisms of apoptosis-related genes and their impact on the response to chemotherapy and survival of patients with colorectal cancer.

Patients and methods: A total of 76 patients with recurrent or metastatic colorectal cancer treated with capecitabine and oxaliplatin (XELOX) combination chemotherapy were enrolled in the present study. The single nucleotide polymorphisms of 15 apoptosis-related genes (TP53, BCL2L, TNFRSF10B, AKT1, PTGS2/COX2, BID, RIPK1, FAS, FASL, caspase 3, and caspase 6-10) were determined using a PCR-RFLP assay.

Results: No significant association between the polymorphisms and the response was found for any of the genes analyzed. However, the T/T genotype of PTGS2 8473T>C (rs5275) was significantly correlated with a better progression-free survival (PFS) and overall survival (OS) when compared to the combined T/C and C/C genotype (Hazard ratio [HR] = 0.47; P value = 0.046 and HR = 0.16; P = 0.013, respectively) in a multivariate analysis adjusted for age, sex, performance status, disease status and curative resection. No association was noted between the other polymorphisms and survival.

Conclusion: The PTGS2 8473T>C polymorphism was found to be correlated with PFS and OS in patients with advanced colorectal cancer treated with XELOX chemotherapy.

MeSH terms

  • Aged
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Capecitabine
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics*
  • Cyclooxygenase 2 / genetics*
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Disease Progression
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / analogs & derivatives
  • Genes, Transgenic, Suicide / genetics
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Organoplatinum Compounds / administration & dosage
  • Oxaliplatin
  • Polymorphism, Genetic / genetics
  • Prognosis
  • Survival Analysis

Substances

  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents
  • Organoplatinum Compounds
  • Oxaliplatin
  • Deoxycytidine
  • Capecitabine
  • Cyclooxygenase 2
  • Fluorouracil