微小RNA变体miR-1206与儿童急性淋巴细胞白血病中氨甲蝶呤诱导的口腔黏膜炎相关。
The miR-1206 microRNA variant is associated with methotrexate-induced oral mucositis in pediatric acute lymphoblastic leukemia.
作者信息
Gutierrez-Camino Angela, Oosterom Natanja, den Hoed Marissa A H, Lopez-Lopez Elixabet, Martin-Guerrero Idoia, Pluijm Saskia M F, Pieters Rob, de Jonge Robert, Tissing Wim J E, Heil Sandra G, García-Orad Africa, van den Heuvel-Eibrink Marry M
机构信息
aDepartment of Genetics, Physical Anthropology and Animal Physiology, Faculty of Medicine and Nursery bBioCruces Health Research Institute, University of the Basque Country (UPV/EHU), Leioa, Spain cPrincess Máxima Center for Pediatric Oncology, Utrecht dDepartment of Clinical Chemistry, Erasmus Medical Center eDepartment of Pediatric Oncology/Hematology, Erasmus Medical Center-Sophia's Children's Hospital, Rotterdam fDepartment of Clinical Chemistry, VU Medical Center, Amsterdam gDepartment of Pediatric Oncology, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands hDepartment of Oncology, St Jude Children's Research Hospital, Memphis, Tennessee, USA.
出版信息
Pharmacogenet Genomics. 2017 Aug;27(8):303-306. doi: 10.1097/FPC.0000000000000291.
Five-year survival rates of pediatric acute lymphoblastic leukemia (ALL) have reached 90% in the developed countries. However, toxicity because of methotrexate (MTX) occurs frequently. Variety in the occurrence of toxicity is partly determined by single nucleotide polymorphisms (SNPs) in coding regions. Recently, five SNPs in non-coding pre-microRNAs and microRNA processing (miRNA) genes were identified in association with MTX-induced oral mucositis. This study aimed to replicate the association of these miRNA variants in relation to MTX-induced oral mucositis in a prospective childhood ALL cohort. Three out of five SNPs with a minor allele frequency more than 0.15 [CCR4-NOT transcription complex (CNOT4) rs3812265, miR-1206 rs2114358, miR-2053 rs10505168] were analyzed in 117 pediatric ALL patients treated with 5 g/m MTX (DCOG ALL-10). Oral mucositis was defined as grade more than or equal to 3 according to the National Cancer Institute criteria. rs2114358 in miR-1206 was associated with oral mucositis [odds ratio (OR): 3.6; 95% confidence interval (CI): 1.1-11.5], whereas we did not confirm the association of CNOT4 rs3812265 (OR: 0.69; 95% CI: 0.27-1.80) and miR-2053 rs10505168 (OR: 2.50; 95% CI: 0.76-8.24). Our results replicate the association between rs2114358 in miR-1206 and MTX-induced oral mucositis in childhood ALL. Genetic variation in miR-1206 has potential as a novel biomarker to predict MTX-induced toxicity.
在发达国家，小儿急性淋巴细胞白血病（ALL）的五年生存率已达到90%。然而，甲氨蝶呤（MTX）引起的毒性反应却频繁发生。毒性反应发生的差异部分由编码区的单核苷酸多态性（SNP）决定。最近，已确定非编码前体微小RNA和微小RNA加工（miRNA）基因中的五个SNP与MTX诱导的口腔黏膜炎有关。本研究旨在在前瞻性儿童ALL队列中重现这些miRNA变异与MTX诱导的口腔黏膜炎之间的关联。在117例接受5 g/m MTX治疗的小儿ALL患者（DCOG ALL - 10）中，分析了五个次要等位基因频率大于0.15的SNP中的三个[CCR4 - NOT转录复合体（CNOT4）rs3812265、miR - 1206 rs2114358、miR - 2053 rs10505168]。根据美国国立癌症研究所标准，口腔黏膜炎定义为3级及以上。miR - 1206中的rs2114358与口腔黏膜炎相关[比值比（OR）：3.6；95%置信区间（CI）：1.1 - 11.5]，而我们未证实CNOT4 rs3812265（OR：0.69；95% CI：0.27 - 1.80）和miR - 2053 rs10505168（OR：2.50；95% CI：0.76 - 8.24）的相关性。我们的结果重现了miR - 1206中的rs2114358与儿童ALL中MTX诱导的口腔黏膜炎之间的关联。miR - 1206中的基因变异有潜力作为预测MTX诱导毒性的新型生物标志物。
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