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

摘要/Abstract

摘要： 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)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%。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、手足综合征、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。

关键词: 基因多态性, 二氢嘧啶脱氢酶, 5-氟尿嘧啶, 结肠癌

Abstract: 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.

Key words: 5-fluorouracil, Dihydropyrimidine dehydrogenase, Colon cancer, Gene polymorphism

中图分类号:

R394

王尧, 陈艳红, 陈宏. 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[J]. 山东大学学报（医学版）, 2014, 52(S1): 18-21.

WANG Yao, CHEN Yan-hong, CHEN Hong. Correlation between sensibility, and side effects of 5-FU and DPYD gene polymorphisms in periphrel blood of patients with colon cancer[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2014, 52(S1): 18-21.

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