肺癌化疗期间侵袭性真菌感染危险因素及细胞色素CYP2C19基因多态性

Risk factors for invasive fungal infection in lung cancer patients during chemotherapy and cytochrome CYP2C19 gene polymorphism

  • 摘要: 目的 肺癌患者化疗期间侵袭性真菌感染(IFI)危险因素及细胞色素CYP2C19基因多态性分析。方法 选择郑州大学第一附属医院肿瘤科2018年1月-2020年1月收治的原发性肺癌患者83例为研究对象,根据其放化疗期间是否发生IFI分为IFI组(n=26)及非IFI组(n=57)。通过电子病历调查收集两组患者住院期间临床资料,分析肺癌患者化疗期间IFI危险因素。采用DNA测序法检测CY2C19*2和CY2C19*3位点单核苷酸多态性。结果 单因素分析结果显示肺癌患者化疗期间IFI发生与抗菌药物应用种类、糖皮质激素应用、住院时间有关(P<0.05),与性别、年龄、肿瘤分期、放化疗方式、合并糖尿病、合并高血压无关。多元回归Logistic分析结果显示,抗菌药物应用种类≥3种、糖皮质激素应用、住院时间≥21 d是肺癌患者发生IFI的独立危险因素(P<0.05);IFI组患者快代谢型、中代谢型、慢代谢型基因型频率分别为30.77%、57.69%、11.54%,三型患者游离型药物浓度分别为(1.87±0.66)mg/ml、(2.49±0.68)mg/ml、(3.33±0.78)mg/ml,差异具有统计学意义(P<0.05)。结论 在临床中应根据危险因素加强对肺癌患者IFI的针对性预防,CYP2C19多态性对于患者伏立康唑药物浓度有一定影响,可用于抗真菌用药指导。

     

    Abstract: OBJECTIVE To explore the risk factors for invasive fungal infection(IFI) in the lung cancer patients and analyze the cytochrome CYP2 C19 gene polymorphism. METHODS Totally 93 primary lung cancer patients who were treated in oncology department of the First Affiliated Hospital of Zhengzhou University from Jan 2018 to Jan 2020 were recruited as the study objects and divided into the IFI group with 26 cases and the non-IFI group with 57 cases according to the status of IFI during the chemotherapy. The clinical data were collected from the two groups of hospitalized patients through review of electronic medical records, and the risk factors for IFI during the chemotherapy were analyzed. The single nucleotide polymorphisms of CY2 C19*2 and CY2 C19*3 loci were detected by means of DNA sequencing method. RESULTS The result of univariate analysis showed that the incidence of IFI in the lung cancer patients was associated with type of antibiotic, use of glucocorticoids and length of hospital stay during the chemotherapy(P<0.05), but it was not associated with the gender, age, tumor stage, mode of chemoradiotherapy, complication with diabetes mellitus or complication with hypertension. Multivariate logistic regression analysis indicated that use of antibiotics no less than 3 types, use of glucocorticoids and length of hospital stay no less than 21 days were the independent risk factors for IFI(P<0.05). The frequencies of fast metabolism-type, moderate metabolism-type and slow-metabolism genotypes of the IFI group were respectively 30.77%, 57.69% and 11.54%, the free drug concentrations of the three types of patients were respectively(1.87±0.66)mg/ml,(2.49±0.68)mg/ml and(3.33±0.78)mg/ml, and there were significant differences(P<0.05). CONCLUSION It is necessary for the hospital to take targeted prevention measures for the lung cancer patients according to the risk factors. The CYP2 C19 polymorphism has certain impact on the concentration of voriconazole, which can provide guidance for antifungal drug therapy.

     

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