title: Promoter polymorphism of MRP1 associated with reduced survival in hepatocellular carcinoma.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  the MRP1 -1666GG genotype predicted a worse outcome and was an independent predictor of poor survival in patients with HCC from Southeast China.
authors.affiliation: 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.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Bing-Yun
authors.initials: BY
authors.lastname: Yu
authors.forename: Dao-Yuan
authors.initials: DY
authors.lastname: Wang
authors.forename: Jin-E
authors.initials: JE
authors.lastname: Yang
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000401:mortality; D002681:China; D018572:Disease-Free Survival; D005260:Female; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D015996:Survival Rate
chemical_list: D027425:ATP-Binding Cassette, Sub-Family C Proteins; C421109:multidrug resistance-associated protein 1