舒尼替尼诱导携带CYP3A4 rs4646437 A等位基因的转移性肾细胞癌患者发生高血压。
Sunitinib-induced hypertension in CYP3A4 rs4646437 A-allele carriers with metastatic renal cell carcinoma.
作者信息
Diekstra M H, Belaustegui A, Swen J J, Boven E, Castellano D, Gelderblom H, Mathijssen R H, García-Donas J, Rodríguez-Antona C, Rini B I, Guchelaar H-J
机构信息
Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands.
Dutch Working Group Focusing on Genotype-related Sunitinib-induced Toxicity (SUTOX Consortium), Leiden, The Netherlands.
出版信息
Pharmacogenomics J. 2017 Jan;17(1):42-46. doi: 10.1038/tpj.2015.100. Epub 2016 Jan 26.
The single nucleotide polymorphism (SNP) rs4646437G>A in CYP3A4 was suggested to be related to sunitinib toxicity. Our objective was to perform an in-depth investigation of the association between this SNP and sunitinib toxicity and efficacy using a large cohort of metastatic renal cell carcinoma (mRCC) patients. We collected DNA and clinical information of mRCC patients treated with sunitinib. SNP rs4646437 in CYP3A4 was tested for associations with toxicity using logistic regression. Cox regression modeling was used for association analysis of rs4646437 with progression-free survival (PFS) and overall survival (OS). In a total of 287 patients, the A-allele of CYP3A4 rs4646437 was associated with an increased risk for hypertension (odds ratio=2.4, 95% confidence interval: 1.1-5.2, P=0.021) and showed no significant association with PFS or OS. In conclusion, hypertension is more likely to occur in A-allele carriers of the CYP3A4 rs4646437 variant in our cohort of mRCC patients treated with sunitinib.
细胞色素P450 3A4（CYP3A4）中的单核苷酸多态性（SNP）rs4646437G>A被认为与舒尼替尼毒性有关。我们的目的是使用一大群转移性肾细胞癌（mRCC）患者，对该SNP与舒尼替尼毒性及疗效之间的关联进行深入研究。我们收集了接受舒尼替尼治疗的mRCC患者的DNA和临床信息。采用逻辑回归分析CYP3A4基因中的SNP rs4646437与毒性之间的关联。使用Cox回归模型分析rs4646437与无进展生存期（PFS）和总生存期（OS）之间的关联。在总共287例患者中，CYP3A4 rs4646437的A等位基因与高血压风险增加相关（比值比=2.4，95%置信区间：1.1-5.2，P=0.021），且与PFS或OS无显著关联。总之，在我们接受舒尼替尼治疗的mRCC患者队列中，CYP3A4 rs4646437变异的A等位基因携带者更易发生高血压。
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