Silenced gene may foretell colon cancer

A genetic defect present in many colorectal tumors can also occur in healthy colon or rectal tissues, a new study finds. This suggests that the defect could play a role in the cancer’s origins and thus could become part of a screening test for identifying people at risk of developing colorectal cancer.

Past research has shown that the gene for O⁶-methylguanine-DNA methyltransferase (MGMT), a protein with tumor-suppressing properties, is silenced in many colorectal tumors. MGMT normally plays a role in DNA repair, but when the promoter region near the MGMT gene acquires a group of methyl molecules, the gene switches off and MGMT production stops.

In the new study, researchers in Texas and Arizona examined colorectal tumors removed from 36 cancer patients. The team also examined samples of healthy tissue taken from 1 centimeter and 10 cm away from each tumor. Lab results indicated that 18 of the tumors had a methylated MGMT promoter. Among the patients who had these tumors, 13 also had methylated MGMT promoters in adjacent healthy tissue and 10 had methylated MGMT promoters in the healthy tissue collected 10 cm away from the tumor, researchers report in the Sept. 21 Journal of the National Cancer Institute.

Many physicians recommend that any person over 50 get colonoscopy screening for cancer at least every 10 years, or more often if there’s a family history of the disease. A test for MGMT genes silenced by a methylated promoter could identify people at high risk of cancer but who show no obvious signs during colonoscopies. These people would benefit from more-frequent colonoscopy screening, says study coauthor Jean-Pierre J. Issa, an oncologist at the M.D. Anderson Cancer Center in Houston.