Meta-analysis of the Association of 3 Kinds of Gene Polymorphisms with High-dose Methotrexate-induced ADR in Osteosar- coma Patients
- VernacularTitle:骨肉瘤患者3种基因多态性与大剂量甲氨蝶呤不良反应相关性的Meta分析
- Author:
Zaiwei SONG
1
,
2
,
3
;
Shuang LIU
1
,
2
,
3
;
Zhanmiao YI
1
,
2
,
3
;
Enyao ZHANG
1
;
Rongsheng ZHAO
1
Author Information
1. Dept. of Pharmacy，Peking University Third Hospital，Beijing 100191，China
2. Dept. of Pharmacy Administration and Clinical Pharmacy，School of Pharmaceutical Sciences，Peking University，Beijing 100191，China
3. Center for Drug Evaluation，Peking University Health Science Center，Beijing 100191，China
- Publication Type:Journal Article
- Keywords:
High-dose methotrexate;
ADR;
Osteosarcoma;
Gene polymorphism;
Meta-analysis
- From:
China Pharmacy
2019;30(15):2135-2143
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE： To systematically evaluate the effects of MTHFR， RFC1 and MDR1 gene polymorphisms on high- dose methotrexate-induced ADR in osteosarcoma patients， and to provide evidence-based reference for individual medication of high-dose of methotrexate. METHODS： Retrieved from Medline， Embase， clinical trials.gov， CNKI， Wanfang database and CBM， cohort studies about the association of MTHFR C677T/A1298C， RFC1 G80A， MDR1 C3435T gene polymorphisms with high-dose methotrexate-induced ADR were collected. After data extraction of clinical studies met inclusion criteria， and quality evaluation with the Newcastle-Ottawa Scale， Meta-analysis and descriptive analysis were performed for outcome indexes as the incidence of high-dose methotrexate-induced ADR （hematotoxicity and myelosuppression， hepatotoxicity， nephrotoxicity， oral mucositis， digestive tract toxicity and overall adverse events） with Rev Man 5.3 and Microsoft Excel 2016 software. RESULTS： Totally 8 cohort studies involving 608 patients were included； 6， 5， 4 and 2 studies reported outcome indexes related to MTHFR C677T/A1298C， RFC1 G80A and MDR1 C3435T gene polymorphisms respectively. Meta-analysis and descriptive analysis showed that MTHFR C677T gene polymorphism was significantly associated with the risk of G3-4 renal toxicity [TT/CT vs. CC： OR＝12.35， 95％CI＝（3.28，46.42）， P＜0.001]， G3-4 oral mucositis [T vs. C： OR＝2.04， 95％CI＝（1.06，3.93）， P＝0.03]， oral mucositis [（TT vs. CT/CC： OR＝2.27， 95％CI＝（1.20，4.27）， P＝0.01] and renal toxicity （P＜0.05）； MTHFR A1298C gene polymorphism was associated with G3-4 hepatotoxicity， G3-4 nephrotoxicity and G3-4 oral mucositis， without statistical significance （P＞0.05）. There was no significant correlation between RFC1 G80A polymorphism and hemotoxicity， hepatotoxicity， nephrotoxicity and digestive tract toxicity （P＞0.05）. MDR1 C3435T polymorphism was significantly correlated with oral mucositis （P＜0.05）， but not with hematotoxicity and hepatotoxicity （P＞0.05）. CONCLUSIONS： MTHFR C677T mutation can increase the risk of high-dose methotrexate-induced ADR. There is no significant association between MTHFR A1298C polymorphism and high-dose methotrexate-induced ADR. There are few studies on RFC1 G80A or MDR1 C3435T polymorphism and high-dose methotrexate-induced ADR， and their association is unclear.
