title: The influence of genetic variants of sorafenib on clinical outcomes and toxic effects in patients with advanced renal cell carcinoma.
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.
authors.affiliation: Department of Urology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Qin
authors.affiliation: Department of Urology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Cao
authors.affiliation: Department of Urology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Pu
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Urology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Shangqian
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Cancer Center of Nanjing Medical University, Department of Molecular &Genetic Toxicology, Nanjing Medical University, Nanjing, China.
authors.forename: Meilin
authors.initials: M
authors.lastname: Wang
authors.affiliation: Cancer Center of Nanjing Medical University, Department of Molecular &Genetic Toxicology, Nanjing Medical University, Nanjing, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Chu
authors.affiliation: Department of Urology, Peking University Fist Hospital, Beijing, China.
authors.forename: Liqun
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Urology, Peking University Fist Hospital, Beijing, China.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Urology, Fu Dan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Dingwei
authors.initials: D
authors.lastname: Ye
authors.affiliation: Department of Urology, Fu Dan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Hailiang
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Urology, Shanghai Renji Hospital, Shanghai, China.
authors.forename: Yiran
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Urology, Shanghai Renji Hospital, Shanghai, China.
authors.forename: Baijun
authors.initials: B
authors.lastname: Dong
authors.affiliation: Department ofOncology, Jiangsu Cancer Hospital, Nanjing, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Urology, Jiangsu Cancer Hospital, Nanjing, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zou
authors.affiliation: Department of Urology, Jiangsu Cancer Hospital, Nanjing, China.
authors.forename: Hongzhou
authors.initials: H
authors.lastname: Cai
authors.affiliation: Department of Urology, the Affiliated Hospital of Qing Dao University, Qiang Dao, China.
authors.forename: Lijiang
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Urology, Nantong Hospital of Traditional Chinese Medicine, Nantong, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Urology, Nanjing Jiangning Hospital, Nanjing, China.
authors.forename: Fade
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Urology, Nanjing Jiangning Hospital, Nanjing, China.
authors.forename: Junbiao
authors.initials: J
authors.lastname: Ji
authors.affiliation: Department of Urology, the First People's Hospital of Changzhou, Changzhou, China.
authors.forename: Li
authors.initials: L
authors.lastname: Cui
authors.affiliation: Department of Urology, Yangzhou NO.1 People's Hospital, Yangzhou, China.
authors.forename: Xiaoxiang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Urology, Yangzhou NO.1 People's Hospital, Yangzhou, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Urology, Jiangyin People's Hospital, Jiangyin, China.
authors.forename: Hu
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Urology, Jiangyin People's Hospital, Jiangyin, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wu
authors.affiliation: Department of Urology, Wujiang NO.1 People's Hospital, Wujiang, China.
authors.forename: Jianchun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Urology, Wujiang NO.1 People's Hospital, Wujiang, China.
authors.forename: Minjun
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Cancer Center of Nanjing Medical University, Department of Molecular &Genetic Toxicology, Nanjing Medical University, Nanjing, China.
authors.forename: Zhengdong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Urology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Shao
authors.affiliation: Department of Urology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Ju
authors.affiliation: Department of Urology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Changjun
authors.initials: C
authors.lastname: Yin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D060831:Hand-Foot Syndrome / Q000235:genetics / Q000401:mortality; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D009536:Niacinamide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D010671:Phenylurea Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D011110:Polymorphism, Genetic; D000077157:Sorafenib; D015996:Survival Rate
chemical_list: D009363:Neoplasm Proteins; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib
references.citation: Curr Oncol Rep. 2010 Mar;12(2):102-8
references.pmid: 20425594
references.citation: J Pathol. 2010 Jun;221(2):125-38
references.pmid: 20225241
references.citation: N Engl J Med. 2005 Dec 8;353(23):2477-90
references.pmid: 16339096
references.citation: Ther Drug Monit. 2007 Jun;29(3):305-12
references.pmid: 17529887
references.citation: Clin Cancer Res. 2011 Feb 1;17(3):620-9
references.pmid: 21097692
references.citation: Cancer Treat Rev. 2005 Nov;31(7):536-45
references.pmid: 16236454
references.citation: N Engl J Med. 2007 Jan 11;356(2):125-34
references.pmid: 17215530
references.citation: Cancer. 2012 Apr 1;118(7):1946-54
references.pmid: 21882181
references.citation: Clin Cancer Res. 2009 Sep 1;15(17):5297-302
references.pmid: 19706811
references.citation: Nat Rev Cancer. 2003 Oct;3(10):721-32
references.pmid: 13130303
references.citation: CA Cancer J Clin. 2013 Jan;63(1):11-30
references.pmid: 23335087
references.citation: Lancet Oncol. 2011 Nov;12(12):1143-50
references.pmid: 22015057
references.citation: Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3473-8
references.pmid: 10716719
references.citation: Ann Oncol. 2012 Apr;23(4):981-9
references.pmid: 21778301
references.citation: Clin Cancer Res. 2009 Feb 15;15(4):1411-6
references.pmid: 19228742
references.citation: J Clin Oncol. 2009 Sep 10;27(26):4406-12
references.pmid: 19667267
references.citation: Curr Top Med Chem. 2012;12(15):1649-59
references.pmid: 22978339
references.citation: J Clin Oncol. 2011 Jun 20;29(18):2557-64
references.pmid: 21576632
references.citation: Onco Targets Ther. 2014 Jun 06;7:925-35
references.pmid: 24944516
references.citation: Cancer. 1995 Sep 1;76(5):824-32
references.pmid: 8625186