We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Genetic predisposition of hand-foot skin reaction after sorafenib therapy in patients with hepatocellular carcinoma.
- Authors
Lee, Joo Ho; Chung, Young‐Hwa; Kim, Jeong A.; Shim, Ju Hyun; Lee, Danbi; Lee, Han Chu; Shin, Eun‐Soon; Yoon, Jung Hwan; Kim, Byung Ik; Bae, Si Hyun; Koh, Kwang Cheol; Park, Neung‐Hwa
- Abstract
BACKGROUND: Sorafenib currently sets the new standard for advanced hepatocellular carcinoma (HCC). It has been suggested that Asian patients with HCC have increased susceptibility to hand-foot skin reaction (HFSR) related to sorafenib therapy. The authors investigated the association between sorafenib-induced HFSR and genetic polymorphisms in Korean patients with HCC. METHODS: For this prospective cohort study, the authors enrolled 59 consecutive patients with intermediate stage HCC from 5 centers in Korea. All patients received sorafenib 400 mg twice daily in combination with transarterial chemoembolization (TACE). Genotyping was performed on a total of 49 single nucleotide polymorphisms (SNPs) in 8 candidate genes (minor allelic frequency ≥5%). Serum levels of vascular endothelial growth factor (VEGF) and tumor necrosis factor-alpha (TNF-α) were measured using enzyme-linked immunosorbent assays before therapy and 1 month after therapy. RESULTS: During a median treatment period of 18 months, 55 patients (93%) developed sorafenib-induced HFSR, including grade 1 reactions in 15 patients, grade 2 reactions in 27 patients, and grade 3 reaction in 13 patients. The SNPs TNF-α −308GG, VEGF −94GG, VEGF 1991CC, VEGF IVS3-28CC, and uridine diphosphate glucuronosyltransferase 1 family-polypeptide A9 ( UGT1A9) IVS1-37431AA were associated significantly with the development of high-grade (grade 2 or 3) HFSR in univariate analysis ( P < .05). In multivariate analysis, the SNPs VEGF 1991CC (odds ratio, 45.7), TNF-α −308GG (odds ratio, 44.1), and UGT1A9 IVS1-37431AA (odds ratio, 18.7) were identified as independent risk factors for the development of high-grade HFSR ( P = .01, P = .02, and P = .02, respectively). He serum TNF-α level measured 1 month after sorafenib therapy was correlated significantly with the development of high-grade HFSR (odds ratio, 3.56; P = .026). CONCLUSIONS: Differences in the incidence of HFSR may have been caused by ethnic differences in genetic polymorphisms of the TNF-α, VEGF, and UGT1A9 genes, especially in relation to the expression of serum TNF-α after sorafenib therapy. Cancer 2013. © 2012 American Cancer Society.
- Subjects
LIVER cancer; HAND-foot syndrome; DISEASE susceptibility; DRUG side effects; GENETIC polymorphisms; LONGITUDINAL method; VASCULAR endothelial growth factors; TUMOR necrosis factors
- Publication
Cancer (0008543X), 2013, Vol 119, Issue 1, p136
- ISSN
0008-543X
- Publication type
Article
- DOI
10.1002/cncr.27705