胃癌组织TSER多态性与5-Fu体外药敏的关系

目的 探讨胃癌组织胸苷酸合成酶增强子区(TSER)多态性与5-Fu体外药敏的关系。方法 对45例胃癌患者新鲜标本进行体外肿瘤细胞原代培养，用ATP-TCA法检测肿瘤细胞对5-Fu的敏感性并用PCR法检测肿瘤的TSER多态性，分析TSER多态性分布频率与体外药敏有效率的关系。结果 TSER多态性三种基因型频率分布： 2R／2R、2R／3R、3R／3R基因组分别为6.7%(3/45)、31.1%(14/45)和62.2%(28/45)。5-Fu总有效率为33.3%(14/42)。3R／3R基因组26例,有效5例,无效21例,有效率19.2%；（2R／2R、2R／3R）基因组16例，有效 9例，无效7例,有效率56.3%。TSER基因型组之间对5-Fu敏感性存在显著差异性（P<0.05）。结论 TSER多态性对5-Fu化疗敏感性可能有关,基因型检测可能有助于预测胃癌组织对5-Fu化疗敏感性。

Correlation between TSER Polymorphism and Sensitivity of Gastric Cancer Tissue to 5-Flu-orouracil

Objective To investigate correlation between thymidylate synthase enhancer region (TSER) polymorphism and the antitumor activities of 5-fluorouracil (5-Fu) determined by ATP sensitivity assay in vitro. Methods The carcinoma cells isolated from fresh gastric tissue in 45 patients were cultured in vitro.The sensitivity of these cells to 5-Fu were tested using ATP TCA method. TSER genotypes were detected by PCR and the correlation between different of TSER genotypes and its chemosensitivity to 5-Fu was analyzed in this study. Results In all cases, the frequency distribution of TSER 2R／2R、2R／3R and 3R／3R genotypes were 6.7%(3/45)、31.1%(14/45) and 62.2%(28/45), respectively. The overall effective rate of 3R/3R group to 5-Fu was 33.3%(14/42). In 2R／2R and 2R／3R genotype group its effective rate to 5-Fu was 56.3%(9/16), which was significantly higher than that of 3R／3R genotype group（19.2%，P<0.05). Conclusions The results in the present study suggest that the polymorphism of TSER was associated with the antitumor activities of 5 -fluorouracil, indicating that analysis of TSER polymorphisms might be useful to direct 5-fluorourcil based antitumor chemotherapy.