Journal
INTERNATIONAL JOURNAL OF CANCER
Volume 141, Issue 5, Pages 967-976Publisher
WILEY
DOI: 10.1002/ijc.30796
Keywords
Age of Onset; CIMP; Colon Cancer; DNA Methylation; Prognostic Factor
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Funding
- South-Eastern Norway Regional Health Authority
- Stiftelsen Kristian Gerhard Jebsen
- Norwegian Cancer Society [72190 PR-2006-0442]
- Research Council of Norway (through Norwegian Cancer Genomics Consortium) [239961, 218241]
- Centre of Excellence funding scheme [179571]
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The prognostic value of CpG island methylator phenotype (CIMP) in colorectal cancer remains unsettled. We aimed to assess the prognostic value of this phenotype analyzing a total of 1126 tumor samples obtained from two Norwegian consecutive colorectal cancer series. CIMP status was determined by analyzing the 5-markers CAGNA1G, IGF2, NEUROG1, RUNX3 and SOCS1 by quantitative methylation specific PCR (qMSP). The effect of CIMP on time to recurrence (TTR) and overall survival (OS) were determined by uni-and multivariate analyses. Subgroup analyses were conducted according to MSI and BRAF mutation status, disease stage, and also age at time of diagnosis (< 60, 60-74, >= 75 years). Patients with CIMP positive tumors demonstrated significantly shorter TTR and worse OS compared to those with CIMP negative tumors (multivariate hazard ratio [95% CI] 1.86 [1.31-2.63] and 1.89 [1.34-2.65], respectively). In stratified analyses, CIMP tumors showed significantly worse outcome among patients with microsatellite stable (MSS, P < 0.001), and MSS BRAF mutated tumors (P < 0.001), a finding that persisted in patients with stage II, III or IV disease, and that remained significant in multivariate analysis (P < 0.01). Consistent results were found for all three age groups. To conclude, CIMP is significantly associated with inferior outcome for colorectal cancer patients, and can stratify the poor prognostic patients with MSS BRAF mutated tumors.
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