Association of CHFR promoter methylation with disease recurrence in locally advanced colon cancer.

Published

Journal Article

PURPOSE: This study was designed to determine whether DNA methylation biomarkers are associated with recurrence and survival in colon cancer patients. EXPERIMENTAL DESIGN: A retrospective analysis of 82 patients who received curative surgical resection for American Joint Committee on Cancer (AJCC) high-risk stage II or III colon cancer (1999-2007) was conducted. DNA methylation status was quantitatively evaluated by the pyrosequencing method. We preselected three tumor suppressor genes and one locus of interest; CHFR, ID4, RECK, and MINT1. Mean methylation levels of multiple CpG sites in the promoter regions were used for analysis; 15% or more was defined as methylation positive. The association of recurrence-free survival (RFS) and overall survival (OS) with methylation status was analyzed by the log-rank test, Kaplan-Meier method, and Cox proportional hazards model. RESULTS: Methylation levels of ID4, MINT1, and RECK did not correlate with RFS or OS. CHFR was methylation positive in 63% patients. When methylation status was dichotomized (negative or low: <30%, high: ≥30%), patients with CHFR methylation-high (44%) had worse RFS (P = 0.006) and reduced OS (P = 0.069). When stratified by stage, CHFR methylation-high was associated with reduced RFS (P = 0.004) and OS (P = 0.010) in stage III patients. CHFR methylation-high was commonly associated with N2 disease (P = 0.04) and proximal tumors (P = 0.002). Multivariate analysis indicated AJCC T4 disease and CHFR methylation-high (P = 0.001 and P = 0.015, respectively) were independent predictors for recurrence. CONCLUSIONS: The extent of CHFR promoter methylation correlates with RFS, indicating it is a promising epigenetic marker for recurrence.

Full Text

Duke Authors

Cited Authors

  • Tanaka, M; Chang, P; Li, Y; Li, D; Overman, M; Maru, DM; Sethi, S; Phillips, J; Bland, GL; Abbruzzese, JL; Eng, C

Published Date

  • July 1, 2011

Published In

Volume / Issue

  • 17 / 13

Start / End Page

  • 4531 - 4540

PubMed ID

  • 21551253

Pubmed Central ID

  • 21551253

International Standard Serial Number (ISSN)

  • 1078-0432

Digital Object Identifier (DOI)

  • 10.1158/1078-0432.CCR-10-0763

Language

  • eng

Conference Location

  • United States