May 25, 2007

More evidence for COX-2 inhibition as protective mechanism against colorectal cancer

A report published in the May 24, 2007 issue of the New England Journal of Medicine, revealed the finding of researchers from Massachusetts General Hospital, Dana-Farber Cancer Institute, and Brigham and Women’s Hospital that inhibition of cyclooxygenase-2 (COX-2) is the mechanism by which aspirin reduces colorectal cancer risk. Numerous studies have found an association between aspirin use and a reduction in colorectal cancer, yet how the drug works had yet to be confirmed.

"We knew that aspirin can block COX-2 function and that COX-2 is present in the vast majority of colorectal tumors but not in normal colon tissue," lead author Andrew Chan, MD, MPH, of Massachusetts General commented. "Therefore we hypothesized that, if blocking the COX-2 pathway was the mechanism underlying aspirin-associated risk reduction, it should preferentially reduce the incidence of those tumors that rely on COX-2."

Dr Chan and his associates utilized data from 83,000 participants in the ongoing Nurses Health Study and 47,000 men participating in the Health Professionals Follow-Up Study, which collect data concerning diet and disease incidence every two years. Both studies had previously found an association between a lower risk of colorectal cancer and aspirin intake. For the current study, 636 pathology specimens from participants with confirmed colorectal cancer were analyzed for COX-2 expression.

Use of two or more standard aspirin tablets per week was found to reduce the risk of colorectal cancer by 25 percent, yet this reduction only applied to tumors that expressed COX-2. COX-2-negative tumor incidence was found to be the same among aspirin users and nonusers.

Senior author Charles Fuchs, MD, MPH, noted, "These results will allow us to test another hypothesis: that in patients who have had colorectal cancer or polyps in the past, expression of COX-2 in the earlier lesion might indicate those for whom aspirin could reduce the risk of recurrence. Answering that will be our next target."