title: Association of ABCB1 genetic polymorphisms with susceptibility to colorectal cancer and therapeutic prognosis.
abstract: OBJECTIVE
  To evaluate the association of ABCB1 gene polymorphisms with susceptibility to colorectal cancer (CRC) and clinical outcomes of CRC patients with chemotherapy.
  
  
  METHODS
  A case-control study was performed on the C3435T, C1236T and G2677T/A polymorphisms in the ABCB1 gene in 1028 CRC patients and 1230 controls.
  
  
  RESULTS
  We observed that the ABCB1 C3435T and G2677T/A variants as well as the 3435T-1236T-2677T haplotype significantly increased the risk of CRC. The ABCB1 C3435T CT genotype had a significant effect on the time to recurrence (adjusted hazard ratio [HR; 95% CI]: 0.560 [0.355-0.882]; p = 0.012). Moreover, ABCB1 C1236T variant carriers displayed a longer overall survival after postoperative oxaliplatin-based chemotherapy (adjusted HR [95% CI]: 0.354 [0.182-0.692], 0.646 [0.458-0.910], respectively). In addition, 1236TT-2677TT-3435TT haplotype carriers showed a worse progression-free survival (adjusted HR [95% CI]: 1.477 [1.012-3.802]; p = 0.043) and recurrence-free survival (adjusted HR [95% CI]: 2.183 [1.253-3.802]; p = 0.006).
  
  
  CONCLUSIONS
  The ABCB1 polymorphisms might be a candidate pharmacogenomic factor to assess susceptibility and prognosis after oxaliplatin-based chemotherapy for CRC patients.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, China Medical University, Shenyang, Liaoning Province 110001, People's Republic of China.
authors.forename: Huizhe
authors.initials: H
authors.lastname: Wu
authors.forename: Hui
authors.initials: H
authors.lastname: Kang
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.forename: Qinghuan
authors.initials: Q
authors.lastname: Xiao
authors.forename: Yining
authors.initials: Y
authors.lastname: Zhang
authors.forename: Mingjun
authors.initials: M
authors.lastname: Sun
authors.forename: Duo
authors.initials: D
authors.lastname: Liu
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.forename: Haishan
authors.initials: H
authors.lastname: Zhao
authors.forename: Weifan
authors.initials: W
authors.lastname: Yao
authors.forename: Tianhong
authors.initials: T
authors.lastname: Jia
authors.forename: Enhua
authors.initials: E
authors.lastname: Wang
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Zheng
authors.forename: Minjie
authors.initials: M
authors.lastname: Wei
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin