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Sci Rep. 2016 Feb 2;6:20089. doi: 10.1038/srep20089.

The influence of genetic variants of sorafenib on clinical outcomes and toxic effects in patients with advanced renal cell carcinoma.

Author information

1
Department of Urology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
2
Department of Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
3
Cancer Center of Nanjing Medical University, Department of Molecular &Genetic Toxicology, Nanjing Medical University, Nanjing, China.
4
Department of Urology, Peking University Fist Hospital, Beijing, China.
5
Department of Urology, Fu Dan University Shanghai Cancer Center, Shanghai, China.
6
Department of Urology, Shanghai Renji Hospital, Shanghai, China.
7
Department ofOncology, Jiangsu Cancer Hospital, Nanjing, China.
8
Department of Urology, Jiangsu Cancer Hospital, Nanjing, China.
9
Department of Urology, the Affiliated Hospital of Qing Dao University, Qiang Dao, China.
10
Department of Urology, Nantong Hospital of Traditional Chinese Medicine, Nantong, China.
11
Department of Urology, Nanjing Jiangning Hospital, Nanjing, China.
12
Department of Urology, the First People's Hospital of Changzhou, Changzhou, China.
13
Department of Urology, Yangzhou NO.1 People's Hospital, Yangzhou, China.
14
Department of Urology, Jiangyin People's Hospital, Jiangyin, China.
15
Department of Urology, Wujiang NO.1 People's Hospital, Wujiang, China.

Abstract

The purpose of the present study was to investigate whether genetic variants that influence angiogenesis and sorafenib pharmacokinetics are associated with clinical outcomes and toxic effects in advanced renal cell carcinoma patients treated with this drug. One hundred patients with advanced renal cell carcinoma were enrolled. Forty-two polymorphisms in 15 genes were selected for genotyping and analyzed for associations with progression-free survival, overall survival, and toxic effects. We found that rs1570360 in VEGF and rs2239702 in VEGFR2 were significantly associated with progression-free. Specifically, patients carrying the variant genotypes (AG + AA) of these two polymorphisms both had an unfavorable progression-free. In addition, compared with those with the rs2239702 GG genotype, patients with the AG + AA genotype suffered an unfavorable OS. We found that the VEGF rs2010963 CG + GG genotypes had a significantly increased risk of hand-foot syndrome, and the ABCB1 rs1045642 CT + TT genotypes had an increased risk of high blood pressure. Our results suggest that polymorphisms in VEGF and VEGFR2 are associated with sorafenib clinical outcomes, and polymorphisms in VEGF and ABCB1 are associated with sorafenib-related toxicities. Larger studies are warranted to validate our findings.

PMID:
26830973
PMCID:
PMC4735712
DOI:
10.1038/srep20089
[Indexed for MEDLINE]
Free PMC Article

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