Thymidylate synthase haplotype is associated with tumor recurrence in stage II and stage III colon cancer

Pharmacogenetics and Genomics
Georg LurjeHeinz-Josef Lenz

Abstract

Tumor recurrence after curative resection is a major problem in the management of colon cancer therapy. Identifying molecular markers for tumor recurrence is critical for successfully selecting patients who are more likely to benefit from adjuvant chemotherapy. We analyzed the value of thymidylate synthase (TS) and methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms as a prognostic marker in stage II and stage III colon cancer patients treated with 5-fluorouracil-based adjuvant chemotherapy. Between 1987 and 2007, blood samples were obtained from 197 patients with stage II or stage III colon cancer at medical facilities at the University of Southern California. DNA was extracted from peripheral blood, and the genotypes were analyzed using PCR-restriction fragment length polymorphism technique. Patients harboring the TS 3RG/+6-bp haplotype were at greatest risk to develop tumor recurrence [relative risk (RR): 2.25; 95% confidence interval (CI): 1.04-4.85; adjusted P value=0.032]. TS enhancer region 3RG alone (RR: 3.48 years; 95% CI: 1.61-7.54; adjusted P value=0.013) or in combination with TS 1494del6 bp (RR: 3.41 years; 95% CI: 1.33-8.75; adjusted P value=0.044) proved to be adverse prognostic markers in both univari...Continue Reading

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