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

作者：Wu, Huizhe; Kang, Hui; Liu, Yong; Xiao, Qinghuan; Zhang, Yining; Sun, Mingjun; Liu, Duo; Wang, Zhe; Zhao, Haishan; Yao, Weifan; Jia, Tianhong; Wang, Enhua; Zheng, Zhihong; Wei, Minjie^*

来源：Pharmacogenomics, 2013, 14(8): 897-911.

DOI：10.2217/PGS.13.78

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

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% Cl]: 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% Cl]: 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% Cl]: 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.

• 出版日期2013-6
• 单位中国医科大学