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| IJCEM Copyright © 2008-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711 |
Int J Clin Exp Med 2012;5(2):186-194
Original Article
ERCC1 C118T associates with response to FOLFOX4 chemotherapy in colorectal
cancer patients in Han Chinese
Haina Chai, Jie Pan, Xuelin Zhang, Xiaoyan Zhang, Xiaoying Shen, Hang Li, Kehao Zhang, Changqing Yang, Haihui Sheng, Hengjun
Gao
Department of gastroenterology, Institute of digestive disease, Tongji Hospital affiliated to Tongji University, Shanghai, 200065, China;
National Engineering Center for Biochip at Shanghai, Shanghai 201203, China; Department of colorectal surgery, Union Hospital,
Fujian Medical University, Fuzhou, Fujian 350001, China; Department of cerebral surgery, Taizhou Central Hospital, Zhejiang Province
318000, China. *These authors contributed equally to this work.
Received January 11, 2012; accepted March 26, 2012; Epub April 6, 2012; Published April 30, 2012
Abstract: Background: Genetic variations influence treatment outcomes in cancer patients treated with chemotherapy. Detection of
pharmacogenetic markers associated with treatment response may enable doctor to plan more precise and effective treatment
tailoring to individual cancer patients. Methods: A novel oligonucleotide microarray was developed to genotype 13 variations (DPYD*2,
DPYD*5, DPYD*9, TYMS 6 bp Ins/Del, UGT1A1*6, UGT1A1*27, UGT1A1*28, GSTP1 Ile105Val, XRCC1 Arg399Gln, MTHFR C677T,
MDR1 C3435T/A, MDR1 G2677A/T and ERCC1 C118T). The accuracy of genotypes obtained by microarray was assessed by
independent sequencing. 73 patients first diagnosed with colorectal cancer (CRC) were treated with FOLFOX4 chemotherapy. Results:
All genotypes were successfully called by microarray, and were consistent with those identified by independent sequencing except two
TYMS 6 bp Ins/Del genotypes. Patients with CT or TT genotype exhibited a higher probability of response to treatment than those with
CC genotype. No other SNP was found to be associated with treatment response. Furthermore, these SNPs showed no associations
with gastrointestinal, hematological or neurological toxicity. Conclusions: ERCC1 C118T may be a predictive marker of treatment
response to 5-FU/platinum chemotherapy for CRC. The microarray can significantly facilitate the process of detecting genetic variations
and may help doctor plan more effective medication for individual cancer patient. (IJCEM1201002).
Keywords: Single nucleotide polymorphism, 5-FU, platinum, drug response, ERCC1, molecular biomarker
Address all correspondence to:
Dr. Heng-Jun Gao
Department of gastroenterology
Institute of digestive disease
Tongji Hospital affiliated to Tongji University
Shanghai 200065, China.
Tel: 86-21-66111075; Fax: 86-21-56050502
E-mail: hengjun_gao @ shbiochip.com
Dr. Hai-hui Sheng
National Engineering Center for Biochip at Shanghai
151 Libing Road, Shanghai 201203, China.
Tel: 86-21-51320288; Fax: 86-21-51320287
E-mail: haihui_sheng @shbiochip.com
Original Article
ERCC1 C118T associates with response to FOLFOX4 chemotherapy in colorectal
cancer patients in Han Chinese
Haina Chai, Jie Pan, Xuelin Zhang, Xiaoyan Zhang, Xiaoying Shen, Hang Li, Kehao Zhang, Changqing Yang, Haihui Sheng, Hengjun
Gao
Department of gastroenterology, Institute of digestive disease, Tongji Hospital affiliated to Tongji University, Shanghai, 200065, China;
National Engineering Center for Biochip at Shanghai, Shanghai 201203, China; Department of colorectal surgery, Union Hospital,
Fujian Medical University, Fuzhou, Fujian 350001, China; Department of cerebral surgery, Taizhou Central Hospital, Zhejiang Province
318000, China. *These authors contributed equally to this work.
Received January 11, 2012; accepted March 26, 2012; Epub April 6, 2012; Published April 30, 2012
Abstract: Background: Genetic variations influence treatment outcomes in cancer patients treated with chemotherapy. Detection of
pharmacogenetic markers associated with treatment response may enable doctor to plan more precise and effective treatment
tailoring to individual cancer patients. Methods: A novel oligonucleotide microarray was developed to genotype 13 variations (DPYD*2,
DPYD*5, DPYD*9, TYMS 6 bp Ins/Del, UGT1A1*6, UGT1A1*27, UGT1A1*28, GSTP1 Ile105Val, XRCC1 Arg399Gln, MTHFR C677T,
MDR1 C3435T/A, MDR1 G2677A/T and ERCC1 C118T). The accuracy of genotypes obtained by microarray was assessed by
independent sequencing. 73 patients first diagnosed with colorectal cancer (CRC) were treated with FOLFOX4 chemotherapy. Results:
All genotypes were successfully called by microarray, and were consistent with those identified by independent sequencing except two
TYMS 6 bp Ins/Del genotypes. Patients with CT or TT genotype exhibited a higher probability of response to treatment than those with
CC genotype. No other SNP was found to be associated with treatment response. Furthermore, these SNPs showed no associations
with gastrointestinal, hematological or neurological toxicity. Conclusions: ERCC1 C118T may be a predictive marker of treatment
response to 5-FU/platinum chemotherapy for CRC. The microarray can significantly facilitate the process of detecting genetic variations
and may help doctor plan more effective medication for individual cancer patient. (IJCEM1201002).
Keywords: Single nucleotide polymorphism, 5-FU, platinum, drug response, ERCC1, molecular biomarker
Address all correspondence to:
Dr. Heng-Jun Gao
Department of gastroenterology
Institute of digestive disease
Tongji Hospital affiliated to Tongji University
Shanghai 200065, China.
Tel: 86-21-66111075; Fax: 86-21-56050502
E-mail: hengjun_gao @ shbiochip.com
Dr. Hai-hui Sheng
National Engineering Center for Biochip at Shanghai
151 Libing Road, Shanghai 201203, China.
Tel: 86-21-51320288; Fax: 86-21-51320287
E-mail: haihui_sheng @shbiochip.com
