Clinical effects of single nucleotide polymorphisms on drug-related genes in Japanese metastatic renal cell carcinoma patients treated with sunitinib.

Abstract

Although sunitinib is a well-established chemotherapeutic for metastatic renal cell carcinoma (mRCC), there are no robust markers that predict efficacy and toxicity. We analyzed the effect of single nucleotide polymorphisms (SNPs) in genes involved in sunitinib pharmacokinetics on clinical outcomes in Japanese patients with mRCC. We analyzed the effect of SNPs in genes involved in sunitinib pharmacokinetics on the clinical outcome in mRCC patients in a Japanese population. We evaluated seven SNPs in four candidate genes, the transport proteins ATP-binding cassette (ABC) B1 (rs1045642, rs1128503, rs2032582, and rs7779562) and ABCG2 (rs2231142), and the metabolic proteins cytochrome P450 (CYP) 3A4 (rs35599367) and CYP3A5 (rs776746) in 70 patients. No significant association was observed between the genotypes of each SNP and time to dose reduction, progression-free survival, overall survival, and best objective response. Meanwhile, the incidence of grade 2 or greater hypertension and hand-foot syndrome, and multiple adverse events (>3), was significantly higher in patients carrying the ABCB1 rs2032582 GG genotype [odds ratio (OR): 5.37, 95% confidence interval (CI) 1.02-14.63, P=0.035; OR: 3.17, 95% CI 1.06-9.52, P=0.036, OR: 3.35; 95% CI 1.14-9.84; P=0.025, respectively]. In conclusion, our data showed that the ABCB1 rs2032582 GG genotype was associated with individual adverse events' susceptibility among Japanese patients treated with sunitinib in routine clinical settings.