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Aspirin and Gastric Cancer: Reducing Risk

Andrew Chan, MD, MPH
Professor, Medicine, Harvard Medical School
Vice chair, Education, Gastroenterology
Chief, Clinical and Translational Epidemiology Unit
Massachusetts General Hospital
Boston, MA

There is a lot of data now that supports that aspirin can reduce the risk of colorectal cancer, and emerging data that it might be effective and prevention of other types of cancer. We conducted a study to examine whether aspirin might reduce the risk for gastric cancer, which is a very large unmet need, given that gastric cancer is difficult to screen for, and there really isn’t a lot of preventative measures available for it. So in this study, we looked at the association of aspirin and risk of gastric cancer in some large population based cohorts, and did find that aspirin reduced the risk of gastric cancer. But particularly among women, and not so much men. We found that to be very interesting and are now trying to understand if there is a difference in the association of aspirin with gastric cancer in other populations of men and women and to see if that’s going to be highlighting some sex differences in people’s risks.

We know that aspirin has a lot of different mechanisms of action, and many of those seem to be related to prevention of cancer. I think there is clear evidence that it does reduce the synthesis of prostaglandins, which are proteins that can be regulated, or go up in amount when there is inflammation. And this seems to be something that also predisposes areas of the body to cancer. So it could be related to the blockade of prostaglandins synthesis that aspirin relates to, but also other mechanisms; there’s also been emerging data that aspirin has other effects on other pathways that might be responsible for the development of cancer and different parts of the body. There is a lot of research that remains to be done, both across different parts of the body, but also with respect to what aspirin might be doing biologically.

There are very well-established side effects of aspirin treatment. But what isn’t clear is what are some other risk factors for bleeding in the general population. And also, what’s the sort of magnitude of that risk and how big of a concern should it be? That’s important for us to think about when we try to weigh risks and benefits and whether people should go on aspirin. Because you have to weigh the benefits of aspirin on the one hand, which include prevention of cancer and, in many people, prevention of heart disease, you have to weigh that against the risk of bleeding. So having some really firm data on just what the risk is, particularly in subgroups of the population, that may be more likely to need to take aspirin, is really important.

A discussion of risks and benefits is so important and that’s why we conducted these studies. One was to understand the mechanism by which aspirin might reduce risk of colorectal cancer. And we specifically did a randomized trial of aspirin, and found that it seems to be effective in reducing a prostate gland metabolite, which is a potential biomarker for responsiveness to aspirin. So that does suggest the possibility in the future, that we have could offer doctors an opportunity to risk stratify patients before they got an aspirin for prevention of cancer. In other words, those people with high levels of biomarker may be the ones that are more likely to benefit.

We also participated in an analysis of data from a randomized trial of aspirin in an older population of about 19,000 individuals and found that there was an increased risk of bleeding related to the randomized aspirin, which was certainly not surprising. But it did show that it seemed to be very dependent on age. In other words, the older you were, even amongst an already elderly population, that was an important risk factor. But also if you had other illnesses, particularly high blood pressure or chronic kidney disease, or if you smoked, that was also important as a risk factor. So it seems like putting together different risk factors that might have to do with biomarkers, or have to do a clinical features, might be best suitable to kind of think about prevention, and risk stratification for prevention going forward.

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