Colorectal cancer is the third most common cancer in the United States for both men and women, excluding skin cancer. The American Cancer Society estimates that there will be more than 95,000 new cases of colon cancer diagnosed in this country in 2017 and nearly 40,000 new cases of rectal cancer.
A healthy lifestyle — including maintaining a healthy weight, not smoking, and avoiding excessive alcohol consumption — can help reduce your risk of getting colorectal cancer. Many studies have suggested that the regular use of aspirin and other NSAIDs (nonsteroidal anti-inflammatory drugs, such as ibuprofen and naproxen) also lowers the risk.
We asked Memorial Sloan Kettering gastroenterologist Robin Mendelsohn what we know about this connection, and why an aspirin a day is not right for everyone.
How do we know that NSAIDs reduce the risk of colorectal cancer?
The first study to make a link was done in Australia in the 1980s. That research looked at colon cancer and potential associations with many different factors. One of the things it found, which was a surprise, was that regular aspirin use seemed to be protective against colon cancer.
Since then, a number of other studies have indicated that there’s a relationship. Some were designed to look at the connection between aspirin and cardiovascular disease, and others specifically investigated the role of NSAIDs in colorectal health. Many of these trials explored the drugs’ ability to reduce the incidence of colon polyps, which can lead to cancer.
Based on the research, there’s clear evidence for a connection, and from a physiological perspective, it makes sense. But there are still a lot of questions.
How does it work, on a physiological level?
In general, we think that colorectal cancer — and likely cancer in general — can result from an inflammatory process. Over time, chronic inflammation damages DNA, which can in turn lead to cancer. So if you block inflammation, which these drugs do, that should decrease the risk.
Another thing we know is that these drugs block an enzyme called cyclo-oxygenase [COX]. In the body, COX converts a molecule called arachidonic acid into hormone-like compounds called prostaglandins. Research both in animal models and in people has shown that colon cancers have higher-than-normal levels of both prostaglandins and COX, so it makes sense that blocking them might have a direct effect.
Prostaglandins make cells proliferate, and they also block apoptosis, which is programmed cell death. These are two important factors for cancer. But the exact molecular mechanism is not known. There are studies under way to figure it out.
What are we still trying to decipher about these processes?
One interesting discovery is that this relationship appears to affect some people more than others. There’s an interaction between the physiological environment that’s created in the body by regular NSAID use and certain gene variations. Some people seem to have more favorable results from using NSAIDs than others.
Studies have shown different markers for inflammation in different people. So this research is still ongoing to figure out who is more likely to benefit and possibly someday find genetic markers.
How much can NSAIDs reduce colorectal cancer risk?
Various studies indicate that the risk is reduced between 20 and 40%, so it’s not insignificant.
But many uncertainties remain. Colon cancer takes a long time to develop, and we don’t know how many years a person would have to take aspirin to reduce his or her risk. We also don’t know how much one would need to take. Some research suggests a low dose is sufficient, but other research indicates that one would need a higher dose.
What are the downsides of taking an NSAID every day?
It can have serious side effects. Aspirin increases your risk of gastrointestinal bleeding and ulcers. This complication could require blood transfusions and can be fatal.
In addition, some NSAIDs may increase your risk of heart attacks and strokes, which also could be fatal.
What are MSK’s recommendations for people who want to take NSAIDs on a daily basis to reduce their colon cancer risk?
Last April, the US Preventive Services Task Force [USPSTF] released its first-ever recommendations on the use of NSAIDs to reduce the risk of colorectal cancer. But there were many qualifications to those guidelines. The group recommended a daily low-dose aspirin only for adults between the ages of 50 and 59, and only those who have a 10% or greater risk of cardiovascular disease. [Aspirin has also been shown to reduce the formation of blood clots that can lead to heart attacks.]
In addition, these recommendations apply to those who have a life expectancy of ten years or more, so they may not be relevant for people with other serious health conditions. And regular aspirin use is not recommended for people who are at increased risk of bleeding.
At MSK, we recognize that for people who meet the USPSTF guidelines, a daily aspirin may make sense. But this is very much an issue that every patient should discuss with his or her healthcare provider, because of the uncertainty about the dose and how long to take it and the risk of side effects.
In addition, I want to stress that a daily aspirin doesn’t take the place of regular screening for colorectal cancer. MSK’s screening guidelines state that everyone over age 50 should be considered for screening, and people who may have increased risk factors for colorectal cancer due to family history or other factors should discuss screening with their doctor.