Do thymidylate synthase gene promoter polymorphism and the C/G single nucleotide polymorphism predict effectiveness of adjuvant 5-fluorouracil-based chemotherapy in stage III colonic adenocarcinoma?
Do thymidylate synthase gene promoter polymorphism and the C/G single nucleotide polymorphism predict effectiveness of adjuvant 5-fluorouracil-based chemotherapy in stage III colonic adenocarcinoma?
复制标题
胸苷酸合成酶基因启动子多态性和 C/G 单核苷酸多态性是否可以预测 III 期结肠腺癌中基于 5-氟尿嘧啶的辅助化疗的有效性？
DOI：
10.3892/or.18.1.203
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发表时间：
2007
期刊：
影响因子：
4.2
通讯作者：
M. Barten
中科院分区：
文献类型：
--
作者：
F. Prall;C. Ostwald;L. Schiffmann;M. Barten
Since 5-fluorouracil (5-FU)-based chemotherapy has become standard adjuvant treatment for patients with node-positive colonic adenocarcinoma, there has arisen the need for predictive factors. Thymidylate synthase (TS) is a major target of 5-FU's action, and high TS expression in carcinoma cells could reduce its cytostatic effect. Both, a 28-base pair repeat polymorphism and a cytosine vs. guanine single nucleotide polymorphism in the promoter region of the TS gene are known to modulate its expression. All patients with a single, non-metachronous node-positive colonic adenocarcinoma who underwent a potentially curative resection at this institution in the years 1994-2002, and who received adjuvant 5-FU (n=95) were included in this study. Ninety-four of the 95 patients were successfully genotyped: 70 patients were classified as TS gene low-expressors (2R-2R, 2R-3C and 3C-3C), and 24 patients were classified as high-expressors (2R-3G, 3C-3G and 3G-3G). Contrary to the hypothesis, Kaplan-Meier survival analysis did not reveal any differences between the groups (power of 0.8 to detect an absolute survival difference >30%). In a Cox model, venous angioinvasion and the infiltrative pattern of tumour invasion were strong adverse factors. These results argue against a practical role for the TS gene repeat polymorphism or the C/G single nucleotide polymorphism as a predictive factor. However, by careful histopathological examination a high-risk group of node-positive patients can be defined that could be candidates for studies of alternative (more aggressive) adjuvant treatment.
