Association of ABCB1 genetic polymorphisms with susceptibility to colorectal cancer and therapeutic prognosis

Pharmacogenomics. 2013 Jun;14(8):897-911. doi: 10.2217/pgs.13.78.

Abstract

Aim: To evaluate the association of ABCB1 gene polymorphisms with susceptibility to colorectal cancer (CRC) and clinical outcomes of CRC patients with chemotherapy.

Patients & 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).

Conclusion: The ABCB1 polymorphisms might be a candidate pharmacogenomic factor to assess susceptibility and prognosis after oxaliplatin-based chemotherapy for CRC patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Disease-Free Survival
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Haplotypes
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / pathology
  • Organoplatinum Compounds / administration & dosage
  • Oxaliplatin
  • Polymorphism, Single Nucleotide
  • Prognosis*

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Organoplatinum Compounds
  • Oxaliplatin