Published On Nov 20, 2014
Cancer: Take Two Aspirin
The connection between aspirin use and a reduced risk for certain cancers is becoming clearer. MGH researcher Andrew Chan outlines who stands to benefit most.
The lowly aspirin pill has been banishing pain and fever since 1899—and for thousands of years previous to that in various distillations of salicylic acid, which is found in willow and myrtle. Known since the 1970s to reduce the risk of heart attack and stroke, aspirin has recently added another potent property —cancer prophylaxis.
Multiple studies, including randomized controlled trials, have now shown that a daily dose of aspirin may not only help to prevent cancers—colorectal, esophageal, stomach, lung, prostate, and breast-- but also may block their spread. The greatest measured impact to date is on colorectal cancer.
Aspirin can lower its incidence by 24% and improve survival by 35% among those who have cancer, according to Andrew T. Chan, Program Director of the gastroenterology training program at MGH and an Associate Professor of Medicine at Harvard Medical School. Chan is a world authority on aspirin, studying the link between aspirin and colon cancer for the last decade, and explains what aspirin can and can’t do.
Q: When did researchers first suspect that aspirin might have anti-cancer properties?
A: In the ‘80s and ‘90s, epidemiological studies showed that individuals who took daily aspirin seemed to have a lower risk of colorectal cancer, evidence that was bolstered by lab studies in cell lines and in animals.
By 2005, data from randomized controlled trials provided causal evidence that aspirin reduces the risk of precancerous colorectal polyps. More recently, trial data has confirmed a reduction in risk of colorectal cancer.
Q: Aspirin appears to lower the risk of several cancers, but its effect seems to be strongest in the colon. Why?
A: We’re not sure why, since we have yet pinpointed aspirin’s precise anticancer mechanisms. So far, we know that aspirin inhibits the production of proteins known as prostaglandins, which help control the cellular communication that controls how cells proliferate.
Prostaglandins have an effect in other cancer types but they’re particularly critical in colon cancer.
Aspirin may also manipulate Wnt protein signaling pathways, a cellular communication stream that appears to be central to the development of cancer.
And aspirin may improve people’s survival after they develop cancer through its ability to block key properties of platelets, a kind of blood cell, which may play a role in tumor growth by helping tumor cells to evade the body’s immune system. This may lead to a cancer’s spread to other organs.
Q: Is aspirin equally powerful in preventing cancer and in stopping its recurrence?
A: The magnitude of benefit may be similar for both prevention and recurrence, but we don’t know for sure.
Q: What progress has been made since the discovery of this anti-cancer property in 2012?
A: The evidence that aspirin reduces the incidence of colorectal cancer is now undisputed. But now we’re zeroing in on biological markers that will tell us who will benefit from taking aspirin, as well as trying to find the sweet spot of how much aspirin and for how long. However, it’s still important to know that not everyone can avoid cancer by taking a daily aspirin, which carries significant side effects, especially in the elderly.
Q: According to your 2014 research , a specific subset of people can reduce their risk of colon cancer with aspirin.
A: Prostaglandins are produced in the colon, but cells have a natural process that breaks down prostaglandins and disposes of them. The enzyme that breaks down prostaglandins is called 15-PGDH.
People have different levels of 15-PGDH in the lining of their colons. The higher your 15-PGDH level, the more benefit it appears you’ll receive from aspirin. This may be because, aspirin, in cooperation with this enzyme, is able to lower these prostaglandins.
Again, prostaglandins are important because they appear to promote cancer by activating pathways that control cell growth and movement. The hope is that we’ll be able to measure 15-PGDH levels in the normal colon, such as during a colonoscopy when we biopsy polyps, which may tell us who might benefit from daily aspirin.
Q: The story is the same for people who’ve experienced colon cancer. Aspirin appears to helps only a subset avoid a recurrence.
A: Tumors that express a protein called COX-2—about 70% to 80% of colon cancers—respond better to aspirin. COX-2 is one of the principal proteins that enable prostaglandins to cause inflammation.
Aspirin blocks COX-2 and, therefore, inhibits inflammation. Aspirin works even better if the tumor also has a mutation in an enzyme called PI3-kinase, which is present in only 15% of tumors.
PI3-kinase has significant communication, or cross-talk, with COX-2 and prostaglandin pathways, which may explain why tumors with mutations in this enzyme are particularly susceptible to aspirin. If the tumor doesn’t have the enzyme or the protein, aspirin may not work well to prevent the cancer from spreading.
Q: How long do you have to take aspirin daily to get a protective benefit against cancer and at what dose?
A: Polyps are growths in the colon that can turn into cancer. Taking aspirin for three years appears to be sufficient to reduce the risk of developing polyps.
But preventing cancer appears to require aspirin intake for 5 to 10 years, which is the length of time it takes for polyps to become cancerous. So I would say that individuals who decide to take aspirin for cancer prevention probably need to do so for at least 10 years . The optimal dose still isn’t clear.
Q: Do you recommend that your patients take aspirin?
A: I talk to my patients who are at high risk for colon cancer and those who’ve already had cancer. After presenting the options, some decide to take aspirin. Each patient needs to weigh the benefits against the potential risks. I make my patients aware that individuals who take daily aspirin have a two-fold higher risk of gastrointestinal bleeding, particularly if they’re over age 70. Of course, this is also the age group that is at the highest risk of developing colon cancer. So it can get complicated. People who are at strong risk for breast or lung cancer may also be willing to take aspirin, even though the data isn’t yet as conclusive as it is for colon cancer.
Q: Do you take aspirin daily?
A: Yes, I do.