Colon cancer prevention: An ASA up the sleeve?

21. July 2014

For many years already there have been increasing indications that aspirin can prevent bowel cancer in some people. Scientists have now been able to show for the first time who it is who benefit from the blood thinners – a first step in personalised cancer prevention.

For many years, evidence has existed that regular intake of ASA is able to prevent colon cancer. In numerous studies however, the same picture keeps turning up: while some patients apparently benefited from the blood thinner, for others it has been ineffective as a colon cancer preventitive. Scientists from several U.S. institutions have now jointly investigated to find out for which group of people aspirin can reduce the risk of developing colon cancer. Their study appeared in the journal Science Translational Medicine.

It comes down to the amount of one enzyme

A permanently active enzyme named cyclooxygenase-2 (COX-2), also known as prostaglandin synthase-2 (PTGS2), is one of the keys in the development of colon cancer. The enzyme converts arachidonic acid into prostaglandin, which in turn stimulates inflammatory responses. ASA can inhibit this enzyme, or at least if the medication is taken in high doses. Apparently though it also needs a bodily-based accomplice. During the oncogenesis process, 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is an antagonist of cyclooxygenase-2, because 15-PGDH provides a path for the reduction of prostaglandin and occurs in colon cancer tissue only in small amounts.

15-PGDH + anti-inflammatory drug = colon cancer prevention

From previous studies it was already known that the enzyme 15-PGDH when tested on mice and 16 humans amplified the effect of the human anti-inflammatory drug Celecoxib (Celebrex) in the context of colorectal cancer prevention. Where 15-PGDH was nevertheless only present in the intestine in small amounts or not at all present, celecoxib had preventive effects neither in mice nor in humans.

Following on, the scientists then examined whether the observed effects would also apply to ASA because the blood thinner seems, at least in terms of side effects, superior to celecoxib. To this end, they checked to see at what concentrations the enzyme 15-PGDH occurs in the intestines of patients who had, despite prophylactic use of ASA, developed colon cancer.

It comes down to the amounts of 15-PGDH

The researchers were able to show that the positive effect of aspirin in the prevention of colon cancer actually depends on the amount of 15-PGDH in the intestine of the subjects. Among people with high levels of 15-hydroxyprostaglandin dehydrogenase in the gut, ASA acts effectively; among people with low levels of this enzyme it apparently does not. Comforting in this matter is one fact: “About half of the population carry large amounts of 15-PGDH in the gut”, as the researchers mention. In their study, the researchers examined intestinal tissue from 270 patients with colorectal cancer. These patients were either part of the Harvard-based Nurses’ Health Study (NHS) or Health Professionals Follow-up Study (HPFS), in which 127 865 participants were followed for over 30 years.

Personalised colorectal cancer screening

“Our work clearly shows who benefits from a regular ASA intake and who does not”, says study author Sanford Markowitz. The researchers hope to have thus created the basis for personalised decisions about colorectal cancer screening. Since ASA is not free from side effects, stomach bleeding and other unpleasant side effects could be avoided if it is clear that the patient, due to his or her 15-PGDH status, is in any case not suitable for ASA-based colon cancer prevention.

Practical test in development

The scientists are now working to implement their vision of personalised colon cancer prevention into practice. The most cost-effective and simple test possible should in the shortest time-frame be worked into medical practices and hospitals, according to their vision. “During a colonoscopy the gastroenterologist could easily and safely remove an additional tissue sample for a 15-PGDH test”, suggests co-author Andrew Chan. Also remaining on the researchers’ “to-do” list is the task of carrying out a prospective clinical study in which the findings from these observations would be checked against at-risk patients. It would be conceivable, moreover, that in addition to 15-PGDH other factors also play a role when it comes to effectively preventing colon cancer using ASA.


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