APC和MGMT启动子甲基化与台湾结直肠癌患者预后的相关性

The association of methylation in the promoter of APC and MGMT and the prognosis of Taiwanese CRC patients.

作者信息

Chen Shee-Ping, Chiu Sheng-Chun, Wu Chang-Chieh, Lin Shinn-Zong, Kang Jung-Cheng, Chen Yi-Lin, Lin Po-Cheng, Pang Cheng-Yoong, Harn Horng-Jyh

机构信息

Institute of Medical Sciences, Tzu-Chi University, Hualien, Taiwan, Republic of China.

出版信息

Genet Test Mol Biomarkers. 2009 Feb;13(1):67-71. doi: 10.1089/gtmb.2008.0045.

DOI:10.1089/gtmb.2008.0045

PMID:19309276

Abstract

AIMS

The purpose of this study was to investigate the association of methylation in the promoter regions of adenomatous polyposis coli (APC) and O(6)-methylguanine-DNA methyltransferase (MGMT) and the survival of Taiwanese colorectal cancer (CRC) subjects who received 5-fluorouracil (5-FU) adjuvant chemotherapy.

RESULTS

DNA isolated from tumor tissue of 117 CRC subjects was analyzed for the existence of methylation in the promoter regions of APC and MGMT by methylation-specific PCR. Various characteristics of the 117 subjects were recorded and used in the Cox proportional-hazard model analyses. Methylation in the promoter region is 62.4% (73/117) for APC and 60.7% (71/117) for MGMT in our CRC patients. Subjects presenting methylation in the APC promoter demonstrate significantly lower hazards for all causes of death (hazard ratios=0.378, p=0.011) or CRC deaths (hazard ratios=0.426, p=0.039). However, no significant correlation is found between the methylation of MGMT promoter and the prognosis of CRC subjects. In addition, no interaction between 5-FU adjuvant chemotherapy and methylation of the two genes are observed.

CONCLUSIONS

Methylation in the APC promoter may serve as a predictor for the prognosis of Taiwanese CRC patients.

摘要

目的

本研究旨在探讨腺瘤性息肉病 coli（APC）和 O(6)-甲基鸟嘌呤-DNA 甲基转移酶（MGMT）启动子区域甲基化与接受 5-氟尿嘧啶（5-FU）辅助化疗的台湾结直肠癌（CRC）患者生存率之间的关联。

结果

通过甲基化特异性 PCR 分析了 117 例 CRC 患者肿瘤组织中分离的 DNA，以检测 APC 和 MGMT 启动子区域甲基化的存在情况。记录了这 117 例患者的各种特征，并将其用于 Cox 比例风险模型分析。在我们的 CRC 患者中，APC 启动子区域甲基化率为 62.4%（73/117），MGMT 为 60.7%（71/117）。APC 启动子出现甲基化的患者所有原因导致的死亡风险显著降低（风险比=0.378，p=0.011）或 CRC 死亡风险降低（风险比=0.426，p=0.039）。然而，未发现 MGMT 启动子甲基化与 CRC 患者预后之间存在显著相关性。此外，未观察到 5-FU 辅助化疗与这两个基因甲基化之间存在相互作用。