【摘要】 目的探讨胸苷酸合成酶(TS)5′非编码区(UTR)串联重复序列和3′UTR6bp缺失或插入多态性对食管鳞状细胞癌(ESCC)的发生及淋巴结转移的作用。方法从232例ESCC患者和348例健康对照者的外周血中提取白细胞DNA,分别用PCR片段长度和PCRRFLP方法检测TS5′UTR和3′UTR基因型。结果TS5′UTR、3′UTR的基因型和等位基因型分布在ESCC患者与健康对照者中,差异无统计学意义,它们不单独作用于ESCC的发生和发展。但这两种多态性联合分析显示,同时携带3R/3R及6bp+/6bp+基因型的个体,其患ESCC的危险性显著低于携带其他基因型组合的个体(校正OR=0.32,95%CI=0.08～0.92)。5′UTR2R/3R基因型显著增加ESCC淋巴结转移的危险性(校正OR=3.68,95%CI=1.54～8.93)。结论TS5′UTR重复序列多态性和3′UTR缺失多态性联合分析可作为预测ESCC易感性的标志,而5′UTR2R/3R可作为预测ESCC淋巴结转移的候选分子指标。更多还原

【Abstract】 Objective To 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). Methods Peripheral 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. Results The 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%)(χ2=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). Conclusion The 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.更多还原