Pharmacy Department, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital, Campus, Barcelona, Spain.
ReDPyD group from the Spanish Society of Hospital Pharmacy (SEFH), Tenerife, Canarias, Spain.
Oncologist. 2023 May 8;28(5):e304-e308. doi: 10.1093/oncolo/oyad077.
Identifying polymorphisms in the dihydropyrimidine dehydrogenase (DPYD) gene is gaining importance to be able to predict fluoropyrimidine-associated toxicity. The aim of this project was to describe the frequency of the DPYD variants DPYD*2A (rs3918290); c.1679T>G (rs55886062); c.2846A>T (rs67376798) and c.1129-5923C>G (rs75017182; HapB3) in the Spanish oncological patients.
Cross-sectional and multicentric study (PhotoDPYD study) conducted in hospitals located in Spain designed to register the frequency of the most relevant DPYD genetic variants in oncological patients. All oncological patients with DPYD genotype were recruited in the participant hospitals. The measures determined where the presence or not of the 4 DPYD previously described variants.
Blood samples from 8054 patients with cancer from 40 different hospitals were used to determine the prevalence of the 4 variants located in the DPYD gene. The frequency of carriers of one defective DPYD variant was 4.9%. The most frequently identified variant was c.1129-5923C>G (rs75017182) (HapB3), in 2.9%, followed by c.2846A>T (rs67376798) in 1.4%, c.1905 + 1G>A (rs3918290, DPYD2A) in 0.7% and c.1679T>G (rs55886062) in 0.2% of the patients. Only 7 patients (0.08%) were carrying the c.1129-5923C>G (rs75017182) (HapB3) variant, 3 (0.04%) the c.1905 + 1G>A (rs3918290, DPYD2A) and one (0.01%) the DPYD c.2846A>T (rs67376798, p.D949V) variant in homozygosis. Moreover, 0.07% were compound heterozygous patients, 3 carrying the DPYD variants DPYD2A + c.2846A>T, 2 the DPYD c.1129-5923C>G + c.2846A>T and one the DPYD2A + c.1129-5923C>G variants.
Our results demonstrate the relatively high frequency of DPYD genetic variants in the Spanish patient with cancer population, which highlights the relevance of their determination before initiating a fluoropirimidine-containing regimen.
鉴定二氢嘧啶脱氢酶（DPYD）基因中的多态性对于预测氟嘧啶相关毒性变得越来越重要。本项目的目的是描述西班牙肿瘤患者中 DPYD 变异体 DPYD*2A（rs3918290）；c.1679T>G（rs55886062）；c.2846A>T（rs67376798）和 c.1129-5923C>G（rs75017182；HapB3）的频率。
这是一项在西班牙医院进行的横断面和多中心研究（PhotoDPYD 研究），旨在登记肿瘤患者中最相关的 DPYD 遗传变异体的频率。所有具有 DPYD 基因型的肿瘤患者均在参与医院招募。所确定的措施是存在或不存在先前描述的 4 种 DPYD 变异体。
来自 40 家不同医院的 8054 名癌症患者的血液样本用于确定位于 DPYD 基因中的 4 种变异体的流行率。携带一种缺陷型 DPYD 变异体的携带者频率为 4.9%。最常鉴定到的变异体是 c.1129-5923C>G（rs75017182）（HapB3），占 2.9%，其次是 c.2846A>T（rs67376798），占 1.4%，c.1905 + 1G>A（rs3918290，DPYD2A），占 0.7%，c.1679T>G（rs55886062），占 0.2%。只有 7 名患者（0.08%）携带 c.1129-5923C>G（rs75017182）（HapB3）变异体，3 名患者（0.04%）携带 c.1905 + 1G>A（rs3918290，DPYD2A），1 名患者（0.01%）携带 DPYD c.2846A>T（rs67376798，p.D949V）变异体为纯合子。此外，0.07%的患者为复合杂合子，3 名患者携带 DPYD 变异体 DPYD2A + c.2846A>T，2 名患者携带 DPYD c.1129-5923C>G + c.2846A>T，1 名患者携带 DPYD2A + c.1129-5923C>G 变异体。
我们的结果表明，西班牙肿瘤患者中 DPYD 遗传变异体的相对频率较高，这突出了在开始氟嘧啶类药物治疗前确定其的重要性。
