PAMM Laboratory for Pathology, Eindhoven, The Netherlands.
Anal Cell Pathol (Amst). 2010;33(1):1-11. doi: 10.3233/ACP-CLO-2010-0526.
Although the predictive and prognostic value of thymidylate synthase (TS) expression and gene polymorphism in colon cancer has been widely studied, the results are inconclusive probably because of methodological differences. With this study, we aimed to elucidate the role of TS gene polymorphisms genotyping in therapy response in stage III colon carcinoma patients treated with 5-FU adjuvant chemotherapy.
251 patients diagnosed with stage III colon carcinoma treated with surgery followed by 5-FU based adjuvant therapy were selected. The variable number of tandem repeats (VNTR) and the single nucleotide polymorphism (SNP) in the 5'-untranslated region of the TS gene were genotyped.
There was a positive association between tumor T stage and the VNTR genotypes (p=0.05).In both univariate and multivariate survival analysis no effects of the studied polymorphisms on survival were found. However, there was an association between both polymorphisms and age. Among patients younger than 60 years, the patients homozygous for 2R seemed to have a better overall survival, whereas among the patients older than 67 this longer survival was seen by the carriers of other genotypes.
We conclude that the TS VNTR and SNP do not predict response to 5-FU therapy in patients with stage III colon carcinoma. However, age appears to modify the effects of TS polymorphisms on survival.
尽管胸苷酸合成酶（TS）表达和基因多态性在结肠癌中的预测和预后价值已被广泛研究，但结果并不一致，这可能是由于方法学的差异。本研究旨在阐明 TS 基因多态性在接受 5-FU 辅助化疗的 III 期结肠癌患者治疗反应中的作用。
选择了 251 名接受手术治疗后接受 5-FU 辅助治疗的 III 期结肠癌患者。对 TS 基因 5'非翻译区的可变数串联重复（VNTR）和单核苷酸多态性（SNP）进行了基因分型。
肿瘤 T 分期与 VNTR 基因型之间存在正相关（p=0.05）。在单因素和多因素生存分析中，未发现研究的多态性对生存有影响。然而，两种多态性与年龄之间存在关联。在年龄小于 60 岁的患者中，2R 纯合子的患者似乎具有更好的总生存，而在年龄大于 67 岁的患者中，其他基因型的携带者则具有更长的生存时间。
我们得出结论，TS VNTR 和 SNP 不能预测 III 期结肠癌患者对 5-FU 治疗的反应。然而，年龄似乎会改变 TS 多态性对生存的影响。
