Genetic predisposition of hand‐foot skin reaction after sorafenib therapy in patients with hepatocellular carcinoma1. Issue 1 (26th June 2012)

• Record Type: Journal Article
• 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
• Is Part Of: Cancer. Volume 119:Issue 1(2013)
• Page Start: 136
• Page End: 142
• Publication Date: 2012-06-26
• Subjects: Cancer -- Periodicals; Cancer -- Cytopathology -- Periodicals; 616.99405
• DOI: 10.1002/cncr.27705
• Languages: English
• ISSNs: 0008-543X

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="abs1-1" sec-type="section"> <title>BACKGROUND:</title> <p>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.</p> </sec> <sec id="abs1-2" sec-type="section"> <title>METHODS:</title> <p>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.</p> </sec> <sec id="abs1-3" sec-type="section"> <title>RESULTS:</title> <p>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 <italic>TNF</italic>‐α −308GG, <italic>VEGF</italic> −94GG, <italic>VEGF</italic> 1991CC, <italic>VEGF</italic> IVS3‐28CC, and uridine diphosphate glucuronosyltransferase 1 family‐polypeptide A9 (<italic>UGT1A9</italic>) IVS1‐37431AA were associated significantly with the development of high‐grade (grade 2 or 3) HFSR in univariate analysis (<italic>P</italic> < .05). In multivariate analysis, the SNPs <italic>VEGF</italic> 1991CC (odds ratio, 45.7), <italic>TNF</italic>‐α −308GG (odds ratio, 44.1), and <italic>UGT1A9</italic> IVS1‐37431AA (odds ratio, 18.7) were identified as independent risk factors for the development of high‐grade HFSR (<italic>P</italic> = .01, <italic>P</italic> = .02, and <italic>P</italic> = .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; <italic>P</italic> = .026).</p> </sec> <sec id="abs1-4" sec-type="section"> <title>CONCLUSIONS:</title> <p>Differences in the incidence of HFSR may have been caused by ethnic differences in genetic polymorphisms of the <italic>TNF</italic>‐α, <italic>VEGF</italic>, and <italic>UGT1A9</italic> genes, especially in relation to the expression of serum TNF‐α after sorafenib therapy. Cancer 2013. © 2012 American Cancer Society.</p> </sec> </abstract>