Polymorphism of TS 3′-UTR predicts survival of Chinese advanced gastric cancer patients receiving first-line capecitabine plus paclitaxel

Abstract

Capecitabine-containing chemotherapy was widely used in clinic medication. We investigated the association of the thymidylate synthase (TS), methylenetetrahydrofolate reductase (MTHFR), and dihydropyrimidine dehydrogenase (DPD) polymorphisms with the clinical outcome of Chinese advanced gastric cancer patients receiving first-line capecitabine plus paclitaxel. Blood samples were collected prior to treatment from 125 patients with advanced gastric cancer and the TS (two or three repeats of a 28bp sequence in 5'-untranslated region and 6bp insertion or deletion in 3'-untranslated region), MTHFR (C677T) and DPD (IVS14+1G>A) polymorphisms were determined using PCR amplification and Sanger sequencing. The median age of 125 patients was 58years (range, 23-76) with female 42 and male 83, and the response rate, median progression-free survival and overall survival (OS) were 43.2%, 5.2 and 11.0months. The median OS in patients with TS ins6/ins6 genotype (6.8months) was significantly shorter than those in patients with ins6/del6 (11.0months, P=0.016) and del6/del6 (11.5months, P=0.039) genotypes. Cox multivariate analysis also showed that TS ins6/ins6 genotype was the independent poor OS predictor (P=0.001, HR=3.182). No significant associations were found between the polymorphisms of TS 5'-UTR/MTHFR and clinical outcome, and no IVS14+1G>A polymorphism of DPD was found in this study. We first reported that TS 3'-UTR ins6/ins6 genotype could predict the poor survival of advanced gastric cancer patients treated with capecitabine plus paclitaxel, which would be further verified in a large multicenter study.