Gene methylation may indicate colorectal cancer in UC

MedWire News: The altered methylation status of three genes may point to the development of colorectal cancer (CRC) in patients with ulcerative colitis (UC), US investigators have discovered.

UC patients are at increased risk for difficult to detect CRC, particularly in areas of active inflammation. There is therefore a need to identify in these patients markers for CRC that occur in the early stages of carcinogenesis, explain Megan Garity-Park, from the Mayo Clinic in Rochester, Minnesota, and colleagues.

To investigate further, the team used methylation-specific polymerase chain reaction to determine the methylation status of the genes p16, p14, runt-related transcript factor-3 (RUNX3), cyclo-oxygenase-2 (COX-2), E-cadherin, methylated-in-tumor (MINT)1 , MINT31, HPP1, estrogen receptor, and SLC5A8 in CRC tumors and non-neoplastic sections from 114 UC patients with CRC and sections from UC controls.

Amplification of the genes was successful in 96 UC controls, and in 83 tumor samples and 66 non-adjacent, non-neoplastic sections from UC patients with CRC, the researchers report in the American Journal of Gastroenterology.

The prevalence of gene methylation for p16, RUNX3, MINT1, MINT31, and HPP1 was significantly increased in CRC cases compared with controls, while that of COX-2 and E-cadherin was significantly increased in controls compared with cases. In non-neoplastic, non-adjacent tissue, RUNX3, p16, MINT1, MINT31, E-cadherin, and COX-2 remained significantly associated with CRC.

Multivariate analysis revealed that only RUNX3, MINT1, and COX-2 remained significantly associated with CRC, at odds ratios of 12.6, 9.0, and 0.2, respectively. The results were unaffected by the presence of primary sclerosing cholangitis or severity of inflammation.

The presence of both RUNX3 methylated and COX-2 unmethylated forms greatly increased the likelihood of a CRC elsewhere in the colon, with a similar, but smaller, association observed for MINT1 methylation and COX-2 unmethylation.

The team concludes: "These data suggest that RUNX3, MINT1, and COX-2 are strong candidates for prospective studies investigating the strength of this panel to predict the likelihood of certain patients to progress to CRC and/or to identify patients with an increased likelihood to have a neoplasm that may not have been detected by routine biopsy."

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