Dihydropyrimidine dehydrogenase activity and the IVS14+1G>A mutation in patients developing 5FU-related toxicity
Dihydropyrimidine dehydrogenase activity and the IVS14+1G>A mutation in patients developing 5FU-related toxicity
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DOI：
10.1111/j.1365-2125.2007.02869.x
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发表时间：
2007-08-01
影响因子：
3.4
通讯作者：
Milano, Gerard
中科院分区：
文献类型：
--
作者：
Magne, Nicolas;Etienne-Grimaldi, Marie-Christine;Milano, Gerard
已知二氢嘧啶脱氢酶（DPD）缺乏是严重5 FU相关性疾病的主要原因toxicity.center先前已证实，5 FU毒性与外周血单核细胞（PMNC）中测得的低酶活性或German DPD之间存在mutations.center联系。本文提供了最大的一系列病例报告（n = 131）与5 FU相关的毒性，分析了PMNC-DPD活性和IVS 14 +1G > mutation.center A突变（2.2%），在所选的高加索人中观察到IVS 14 + 1G > A突变的发生率非常低（www.example.com）population.center。目的回顾性分析DPD表型/基因型与5-FU毒性强度的关系。对5 FU相关毒性的患者（女性81例，男性50例）进行了分析，DPD活性越低，（10-504 pmol min（-1）mg（-1））时，毒性评分越高（P < 0.01）。9名患者（8名女性）发生毒性相关死亡，他们的DPD活性明显低于其他患者。其中两名死者的DPD活性正常。在93名患者中分析的IVS 14 +1G > A突变在两名患者中检测到（非致死性毒性）JVS 14 +1G > A突变可能无助于防止毒性，并且具有正常DPD活性的患者可能发展危及生命的5 FU毒性。
What is already known about this subjectcenter dot Dihydropyrimidine dehydrogenase (DPD) deficiency is known to be a major cause of severe 5FU-related toxicity.center dot A link has been previously shown between 5FU toxicity and either low enzyme activity measured in peripheral blood mononuclear cells (PMNC) or germinal DPD mutations.center dot The link between the most common DPD mutation (IVS14+1G > A) and PMNC enzyme activity is poorly documented.What this study addscenter dot This paper provides the largest series of case-reports (n = 131) with 5FU-related toxicity, analyzed for both PMNC-DPD activity and the IVS14+1G > A mutation.center dot A very low incidence of the IVS14+1G > A mutation (2.2%) was observed in this selected Caucasian population.center dot Present data suggest that IVS14+1 mutation screening has limited effectiveness in identifying patients at risk for severe 5FU toxicity. Also, patients with normal PMNC-DPD activity may develop life-threatening toxicity.To examine retrospectively the relationship between DPD phenotype/genotype and the intensity of 5FU toxicity.One hundred and thirty-one case-reports (81 women, 50 men) with 5FU-related toxicity were analyzed.The lower the DPD activity (10-504 pmol min(-1) mg(-1)), the higher the toxicity grade was scored (P < 0.01). Toxicity-related deaths occurred in nine patients (eight women) who significantly expressed lower DPD activity than other patients. Two of the deceased patients had normal DPD activity. The IVS14+1G > A mutation, analyzed in 93 patients, was detected in two patients (nonlethal toxicity).The IVS14+1G > A mutation may not help prevent toxicity and patients with normal DPD activity may develop life-threatening 5FU toxicity.