Original Article
Copyright ©2010 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Dec 28, 2010; 16(48): 6104-6110
Published online Dec 28, 2010. doi: 10.3748/wjg.v16.i48.6104
Promoter polymorphism of MRP1 associated with reduced survival in hepatocellular carcinoma
Jing Zhao, Bing-Yun Yu, Dao-Yuan Wang, Jin-E Yang
Jing Zhao, Bing-Yun Yu, Jin-E Yang, Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen (Zhongshan) University, Guangzhou 510275, Guangdong Province, China
Dao-Yuan Wang, Department of Medical Oncology, The First Affiliated Hospital of Guangzhou Medical College, Guangzhou 510120, Guangdong Province, China
Author contributions: Zhao J designed and performed most of the research and wrote the paper; Yu BY performed the experiments; Wang DY performed the statistical analysis; Yang JE designed experiments, analyzed the data, and wrote the paper.
Supported by The Scientific and Technological Program of Guangdong Province, China, No. 2003B30102
Correspondence to: Dr. Jin-E Yang, PhD, Associate Professor, Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen (Zhongshan) University, Xin Gang Xi Road 135#, Guangzhou 510275, Guangdong Province, China. lssyje@mail.sysu.edu.cn
Telephone: +86-20-84115532 Fax: +86-20-84112169
Received: June 9, 2010
Revised: August 30, 2010
Accepted: September 7, 2010
Published online: December 28, 2010
Abstract

AIM: To investigate the effect of the G-1666A polymorphism in the multidrug resistance related protein-1 (MRP1) on outcome of hepatocellular carcinoma (HCC).

METHODS: A cohort of 162 patients with surgically resected HCC who received no postsurgical treatment until relapse was studied. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism analysis. Electrophoretic mobility shift assay (EMSA) was used to evaluate the influence of the G-1666A polymorphism on the binding affinity of the MRP1 promoter with its putative transcription factors.

RESULTS: Kaplan-Meier analysis showed that patients with GG homologues had a reduced 4-year disease-free survival compared with those carrying at least one A allele (P = 0.011). Multivariate Cox regression analysis indicated that the -1666GG genotype represented an independent predictor of poorer disease-free survival [hazard ratio (HR) = 3.067, 95% confidence interval (CI): 1.587-5.952, P = 0.001], and this trend became worse in men (HR = 3.154, 95% CI: 1.604-6.201, P = 0.001). A similar association was also observed between 4-year overall survival and the polymorphism in men (HR = 3.342, 95% CI: 1.474-7.576, P = 0.004). Moreover, EMSA suggested that the G allele had a stronger binding affinity to nuclear proteins.

CONCLUSION: The MRP1 -1666GG genotype predicted a worse outcome and was an independent predictor of poor survival in patients with HCC from Southeast China.

Keywords: Multidrug resistance related protein-1; Single nucleotide polymorphism; Hepatocellular carcinoma; Prognosis