Aspirin’s Action Against Colon Cancer

Two large randomized studies done in UK provide what an editorialist calls “convincing evidence” that aspirin prevents colorectal cancer. Now the USA gets into the act with two more studies, recently published in the New England Journal of Medicine. The Nurses Health Study (121,700 women) and the Health Professionals Follow-up Study (51,500 men) provided the data.

Now for some simplified science. COX-2 is a cyclooxygenase enzyme produced in a number of tissues, often in response to inflammation. It’s been thought, based on the effectiveness of different types of non-steroid anti-inflammatory drugs (and their side effects) that the COX-1 enzyme is specific for intestinal lining cells and COX-2 for pain and inflammation. This was the reason that COX-2 inhibitors, like Vioxx®, improve pain and inflammation without causing gastrointestinal side effects, whereas aspirin (a COX-1 and COX-2 inhibitor) helps pain and inflammation but also irritates the stomach and intestine lining. Why is this important for colon cancer?

The US studies estimated COX-2 levels (called ‘expression’) in cancer tissue taken from 636 colorectal cancers. Of these, two-thirds had moderate or strong COX-2 expression; the remainder was COX-2 negative. However, regular aspirin users had almost half the risk of COX-2 tumors, while they had the same risk for COX-2-negative tumors.

The practical conclusions from these studies are limited. At present there’s no good way to determine which patients are likely to develop COX-2 tumors rather than non-COX-2 tumors, so the benefits of aspirin are a bit hit-and-miss. Of course, if someone has had a polyp removed and this is examined for COX-2 expression, there could be a much better reason for instituting regular aspirin therapy. And the very fact that reduced tumor frequency is tied to COX-2 in some fashion means there’s a starting point for new drug development.