结肠癌患者外周血DPYD基因多态性与5-FU敏感性和毒副作用相关性分析

Correlation between sensibility, and side effects of 5-FU and DPYD gene polymorphisms in periphrel blood of patients with colon cancer

目的探讨结肠癌患者外周血二氢嘧啶脱氢酶(DPYD)基因多态性与5-氟尿嘧啶(5-FU)的敏感性和毒副作用的相关性.方法选取肿瘤科收治的结肠癌患者100例,给予FOLFOX4方案化疗3个周期.提取外周血单核细胞总DNA,采用定量PCR检测DPYD基因14G1A、A1627G、T85C 3个位点的多态性,分析DPYD基因多态性与5-FU敏感性、毒副作用的相关性.结果100例患者中完全缓解(CR)3例部分缓解,(PR)40例,疾病稳定(SD)36例,疾病进展(PD)21例;CR+PR为43.0%.本研究中14G1A、A1627G、T85C均检测有位点突变,其中14G1A位点突变率为14.0%,A1627G位点突变率为11.0%,T85C位点突变率为17.0%.14G1A、A1627G、T85C基因中,野生型的5-FU敏感性高于突变型,差异有统计学意义(P<0.05).14G1A、A1627G、T85C 3个位点突变型在骨髓抑制、手足综合症、腹泻、胃肠道反应、黏膜炎等不良反应发生率方面高于野生型.结论DPYD基因多态性对预测5-FU的疗效和毒性反应有指导作用,可以作为5-FU个性化给药方案的重要参考指标之一.

Objective To explore the association of 5-FU susceptibility and side effects with dihydropyrimidine dehydrogenase(DPYD)gene polymorphism in colon cancer patients.Methods A total of 100 colon cancer patients were recruited and treated with FOLFOX4 regimen.Quantitative PCR were taken to measure DPYD gene polymorphism at loci 14G1A,A1627G,T85C3.Relationship between susceptibility and side effects of 5-FU and gene polymorphism were analyzed.Results 14G1A A1627G,T85C were detected with site mutation,with 14%,11%and 17%of mutant frequencies,respectively.The susceptibility to 5-FU in mutant gene were significantly lower than those in wild-type gene(P<0.05).Adverse reaction rate such as bone marrow inhibition,hand-foot syndrome,diarrhea,gastrointestinal reactions was significantly higher in mutant gene than that of wild-type genes(P<0.05).Conclusion DPYD gene polymorphism may be useful in predicting side reaction of 5-FU.