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多药耐药蛋白 2 基因多态性与接受辅助 FOLFOX-4 化疗的结直肠癌患者的复发。

Multidrug resistance protein 2 genetic polymorphism and colorectal cancer recurrence in patients receiving adjuvant FOLFOX-4 chemotherapy.

机构信息

Department of Pathology, Faculty of Medicine and Health Sciences, University Putra Malaysia, Serdang, Selangor 43400, Malaysia.

出版信息

Mol Med Rep. 2013 Feb;7(2):613-7. doi: 10.3892/mmr.2012.1226. Epub 2012 Dec 7.

DOI:10.3892/mmr.2012.1226
PMID:23232902
Abstract

Multidrug resistance protein 2 (MRP2), encoded by the ATP-binding cassette C2 (ABCC2) gene, is an efflux pump located on the apical membrane of many polarized cells, which transports conjugate compounds by an ATP-dependent mechanism. The correlation of G1249A ABCC2 polymorphism with the development of colorectal cancer (CRC) and poor prognosis was evaluated in patients who were treated with fluorouracil/-leucovorin (FL) plus oxaliplatin (FOLFOX-4). A total of 50 paraffin‑embedded tissue samples collected from CRC patients were analyzed to identify the polymorphism. Patients were in stage II/III and received postoperative FOLFOX-4 chemotherapy. As a control group, an equal number of unrelated healthy subjects were enrolled in the study. The polymorphism was genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, and results were compared with clinicopathological markers, early relapse and survival rates. During the 12 months of follow-up, local and distant recurrences were observed in 15 (30%) patients. No significant difference in the distribution of wild-type and polymorphic genotypes was observed between the patient and control groups and between the patients who experienced recurrence within 1 year and those who did not (all P>0.05). In conclusion, the G1249A polymorphism is not associated with CRC risk and early recurrence. However, significant correlation was observed between G1249A polymorphism and the overall survival and disease-free survival of the patients.

摘要

多药耐药相关蛋白 2(MRP2),由三磷酸腺苷结合盒 C2(ABCC2)基因编码,是一种位于许多极化细胞顶膜的外排泵,通过 ATP 依赖的机制转运结合化合物。在接受氟尿嘧啶/亚叶酸(FL)联合奥沙利铂(FOLFOX-4)治疗的患者中,评估了 G1249A ABCC2 多态性与结直肠癌(CRC)的发生和不良预后的相关性。对 50 例 CRC 患者的石蜡包埋组织样本进行了分析,以确定该多态性。患者处于 II/III 期,并接受了术后 FOLFOX-4 化疗。作为对照组,招募了相同数量的无关健康受试者参加研究。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法对多态性进行基因分型,并将结果与临床病理标志物、早期复发率和生存率进行比较。在 12 个月的随访期间,15 名(30%)患者出现局部和远处复发。患者组和对照组之间以及 1 年内复发和未复发患者之间的野生型和多态基因型分布无显著差异(均 P>0.05)。总之,G1249A 多态性与 CRC 风险和早期复发无关。然而,G1249A 多态性与患者的总生存率和无病生存率显著相关。

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