The association of methylation in the promoter of APC and MGMT and the prognosis of Taiwanese CRC patients.
OBJECTIVE
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.
Chen
Shee-Ping
SP
Institute of Medical Sciences, Tzu-Chi University, Hualien, Taiwan, Republic of China.
Chiu
Sheng-Chun
SC
Wu
Chang-Chieh
CC
Lin
Shinn-Zong
SZ
Kang
Jung-Cheng
JC
Chen
Yi-Lin
YL
Lin
Po-Cheng
PC
Pang
Cheng-Yoong
CY
Harn
Horng-Jyh
HJ
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics*; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D017491:Genes, APC; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011401:Promoter Regions, Genetic; D016019:Survival Analysis; D013624:Taiwan; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D000964:Antimetabolites, Antineoplastic; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D005472:Fluorouracil