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目的:分析VEGFR3基因及CYP3A5*1基因单核苷酸多态性(SNP)在肾癌人群的分布特征,评价其与舒尼替尼药物治疗疗效及耐受性的相关性。方法:2012年6月~2013年6月,对198例肾癌患者进行外周血VEGFR3(rs307826)及CYP3A5*1(rs776746)位点的SNP检测,同时采集患者的自然信息、临床资料、治疗经过及预后。应用统计学方法评价中国人群与欧洲人群这两个基因位点SNP分布差异以及两个基因位点的SNP特征与舒尼替尼治疗晚期肾癌的疗效及耐受性的相关性。结果:VEGFR3(rs307826)位点SNP检测结果:野生型纯合子196例、杂合子2例;CYP3A5*1(rs776746)位点SNP检测结果:野生型纯合子115例、杂合子80例,与欧洲人群分布特征的差异有统计学意义(P<0.01)。45例患者接受舒尼替尼药物治疗,CYP3A5*1(rs776746)SNP结果:野生型纯合子27例、杂合子18例,舒尼替尼初始剂量均为50mg/d,4/2周给药方案,主要不良反应包括高血压、血小板减低、白细胞减低、甲状腺功能低下等,Ⅲ~Ⅳ级不良反应发生率28.9%,15例患者因不良反应进行了剂量调整。结论:VEGFR3基因及CYP3A5*1基因的SNP分布特征在不同种族存在显著差异,CYP3A5*1(rs776746)位点SNP特征与中国肾癌患者接受舒尼替尼治疗的Ⅲ~Ⅳ级不良反应发生率及药物减量风险相关。
OBJECTIVE: To analyze the distribution of VEGFR3 and CYP3A5 * 1 SNPs in renal cell carcinoma and to evaluate their relationship with the efficacy and tolerability of sunitinib. Methods: From June 2012 to June 2013, 198 patients with renal cell carcinoma were enrolled in this study. SNPs of peripheral blood VEGFR3 (rs307826) and CYP3A5 * 1 (rs776746) were detected. Natural information, clinical data and treatment were collected And prognosis. Statistical analysis was used to evaluate the distribution of SNPs in Chinese and European populations and the relationship between the SNP characteristics of the two loci and the efficacy and tolerability of sunitinib in the treatment of advanced renal cell carcinoma. Results: SNP of VEGFR3 (rs307826) was detected in 196 cases of wild-type homozygotes and 2 cases of heterozygotes. SNP of CYP3A5 * 1 (rs776746) was detected in 115 cases of wild-type homozygotes and 80 cases of heterozygotes, There were significant differences in population distribution characteristics (P <0.01). Forty-five patients were treated with sunitinib. SNP of CYP3A5 * 1 (rs776746): 27 wild-type homozygotes and 18 heterozygotes, and the initial dose of sunitinib was 50 mg / d for 4/2 weeks The main adverse reactions included hypertension, thrombocytopenia, leucopenia and hypothyroidism. The incidence of grade Ⅲ-Ⅳ adverse reactions was 28.9%. Fifteen patients underwent dose adjustment due to adverse reactions. CONCLUSIONS: The SNP distributions of VEGFR3 and CYP3A5 * 1 genes are significantly different in different races. The SNP characteristics of CYP3A5 * 1 (rs776746) and the incidence of grade Ⅲ ~ Ⅳ adverse reactions in patients with renal cell carcinoma receiving sunitinib Related to the risk of drug reduction.