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目的:通过文献复习乳腺癌常用化疗药物5-氟尿嘧啶(5-FU)代谢酶基因型多态性与乳腺癌化疗敏感的相关性。方法:以“5-FU,二氢嘧啶脱氢酶(DPD),胸苷酸合酶(TS),5,10-亚甲基四氢叶酸还原酶(MTHFR),基因型多态性,乳腺癌”为关键词,使用PubMed和CNKI数据库对1999-2007年发表的文章进行分别或联合检索,共收集到相关文献185条,通过查找全文,排除重复研究和与本研究无关的文献后,最后精选纳入分析的文献29篇。结果:5-FU在体内代谢过程中,3个关键酶DPD、TS和MTHFR活性的变化会影响到5-FU化疗的有效性和毒副反应,而DPD、TS和MTH-FR活性受到其编码基因的影响,相应基因的多态性使得不同患者对5-FU的反应出现差异。结论:研究DPD、TS和MTHFR基因型多态性,对于判断乳腺癌预后及治疗效果有着重要意义,使得从基因水平上直接检测5-FU的反应成为可能,达到对乳腺癌患者的个体化治疗。
OBJECTIVE: To review the correlation between genotype polymorphism of 5-fluorouracil (5-FU) metabolizing enzyme and chemosensitivity in breast cancer through literature. Methods: The 5 ’- FU, dihydropyrimidine dehydrogenase (DPD), thymidylate synthase (TS), 5,10 - methylenetetrahydrofolate reductase (MTHFR), genotype polymorphism, Breast cancer "as the key words, using PubMed and CNKI database separately or jointly retrieved articles published in 1999-2007, a total of 185 articles were collected, by looking up the full text, excluding duplication of research and literature unrelated to this study , The final selection included in the analysis of 29 articles. Results: The changes of DPD, TS and MTHFR activities of 5-FU in 5-FU metabolism affected the efficacy and toxicity of 5-FU chemotherapy, while the activities of DPD, TS and MTH-FR were affected by their coding Genes, polymorphisms of the corresponding genes led to differences in response to 5-FU in different patients. Conclusion: The study of polymorphism of DPD, TS and MTHFR genotypes is of great significance in judging the prognosis and treatment effect of breast cancer, making it possible to detect the 5-FU reaction directly at the gene level to achieve the individualized treatment of breast cancer patients .