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- Title
Promoter polymorphism of MRP1 associated with reduced survival in hepatocellular carcinoma.
- Authors
Jing Zhao; Bing-Yun Yu; Dao-Yuan Wang; Yang, Jin-E.
- 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.
- Subjects
GENETIC polymorphisms; PROMOTERS (Genetics); MULTIDRUG resistance; LIVER cancer patients; POLYMERASE chain reaction; HEALTH outcome assessment
- Publication
Annals of Gastroenterology & Hepatology, 2011, Vol 9, Issue 93, p6104
- ISSN
2043-023X
- Publication type
Article
- DOI
10.3748/wjg.v16.i48.6104