OBJECTIVETo explore the influence of 5'UTR tandem repeat and 3'UTR 6 bp deletion polymorphism of thymidylate synthase (TS) gene on the development and lymphatic metastases of esophageal squamous-cell carcinoma (ESCC).

METHODSPeripheral leucocyte DNA was extracted from 232 ESCC patients and 348 age- and sex-matched healthy controls. TS 5'UTR and 3'UTR genotyping in all study subjects was performed by PCR fragment analysis and PCR-RFLP analysis, respectively.

RESULTSThe distribution of TS 5'UTR and 3'UTR variants in ESCC patients was not significantly different from that in healthy controls. However, individuals with 6 bp+/6 bp+ and 3R/3R genotypes significantly reduced the risk to ESCC development compared to those with other genotype combinations (adjusted OR = 0.32, 95% CI = 0.08-0.92). In addition, the frequency of 2R/3R genotype in ESCC patients with lymphatic metastases (40%) was significantly higher than that in lymph node negative cases (14.7%) (chi(2) = 10.11, P = 0.001). Compared to 3R/3R genotype, the 2R/3R genotype significantly increased the risk of lymphatic metastases in ESCC (adjusted OR = 3.68, 95% CI = 1.54-8.93).

CONCLUSIONThe genotyping of TS 5'UTR and 3'UTR polymorphisms might be used as a stratification maker for predicting susceptibility to ESCC. The TS 5'UTR 2R/3R genotype might be a candidate molecular marker to predict the potential of lymphatic metastases in ESCC.