CpG Island Methylation in Familial Colorectal Cancer Patients Not Fulfilling the Amsterdam Criteria

ABSTRACT

To determine the role of methylation in colorectal cancer patients with a family history, we enrolled 25 colorectal cancer patients with a family history of colorectal cancer but without a mutation in the hMLH1 and hMSH2 genes. Thirty patients with sporadic colorectal cancer were included as control. The methylation status of COX2, MGMT, hMLH1, TIMP3, p16, and MINT2 in normal mucosa and tumor were assessed using methylation-specific PCR. In patients with a family history, the methylation frequency ranged from 4.0% for TIMP3 to 44.4% for MGMT, whereas, in patients with sporadic colorectal cancer, it ranged from 6.7% for TIMP3 to 50.0% for p16. Nine of the 25 patients with family history (36.0%) were classified as methylation-prone, and nine of the 30 patients with sporadic cancers (30.0%) were as methylation-prone, making their methylation indices 0.19 and 0.16, respectively (p=0.522). As for the individual genes, the methylation rate of MGMT was higher in colorectal cancer patients with family history (44.0% vs. 13.0%, p=0.016), whereas the methylation rate of p16 was higher in sporadic colorectal cancers (50.0% vs. 8.7%, p=0.046). While CpG island methylation of tumor suppressor genes may play a role in colorectal carcinogenesis, the genes involved may be different between tumors of patients with and without a family history of colorectal cancer.