Hypermethylation of the CDKN2A gene in colorectal cancer is associated with shorter survival.

Promoter hypermethylation of the CDKN2A gene has been suspected to be involved in the carcinogenesis of colorectal cancers. However, the relations between CDKN2A hypermethylation and clinicopathological findings, and patient prognosis, remain inconclusive. We analyzed the CDKN2A methylation status in primary colorectal cancers using real-time methylation specific PCR (MethyLight) which enables quantitative measuring of the methylation level. CDKN2A promoter methylation was detectable in 55 (61.1%) of 90 tumor samples and the median level of the methylation was 0.187 (range 0.00-197.9). The methylation value of CDKN2A was correlated with certain clinicopathological findings, including tumor differentiation (p=0.018), and Dukes stage (p=0.016). In survival analysis, the CDKN2A methylation level was correlated with a poor prognosis of the patient with colorectal cancer for either all cases (p=0.014) or Dukes C (p=0.004) cases that were analyzed. These results suggest that CDKN2A methylation status is a prognostic factor in colorectal cancer and may be of use for the patient specific design of therapy.