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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antimetabolites, Antineoplastic / therapeutic use
  • Chemotherapy, Adjuvant
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / enzymology*
  • Colorectal Neoplasms / genetics*
  • DNA Methylation*
  • DNA Modification Methylases / genetics*
  • DNA Repair Enzymes / genetics*
  • Female
  • Fluorouracil / therapeutic use
  • Genes, APC*
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Promoter Regions, Genetic
  • Survival Analysis
  • Taiwan
  • Tumor Suppressor Proteins / genetics*

Substances

  • Antimetabolites, Antineoplastic
  • Tumor Suppressor Proteins
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes
  • Fluorouracil