Association of ABCB1 Genetic Polymorphisms with Susceptibility to Colorectal Cancer and Therapeutic Prognosis

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.

Original submitted 4 January 2013; Revision submitted 10 April 2013

KEYWORDS::

• ABCB1
• colorectal cancer
• fluorouracil
• genetic polymorphisms
• haplotype
• oxaliplatin
• prognosis
• susceptibility

Financial & competing interests disclosure

This work was supported by grants from the National Natural Science Foundation of the Republic of China (project No. 81173092), Science and Technology Project of Shenyang (No. F11-264-1-19, No. F12-148-9-00) and Science and Technology Project of Liaoning province (No. 2011415052). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This work was supported by grants from the National Natural Science Foundation of the Republic of China (project No. 81173092), Science and Technology Project of Shenyang (No. F11-264-1-19, No. F12-148-9-00) and Science and Technology Project of Liaoning province (No. 2011415052). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.