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Does aspirin prevent colorectal cancer? Depends on your DNA

Fred Hutch researchers move closer to cracking the code on how genes and environmental factors influence colorectal cancer risk

March 17, 2015
Aspirin

While regular use of aspirin and NSAIDs was associated with an overall reduced risk of colorectal cancer, there was no such protective effect among about 9 percent of the study participants who carried an uncommon genetic variation on chromosome 15.

Photo by Robert Hood / Fred Hutch News Service

Scientists have found that aspirin and non-steroidal anti-inflammatory drugs, or NSAIDs, can protect against some colorectal cancers.

But don’t pop that pill just yet.

A new study by public health researchers at Fred Hutchinson Cancer Research Center has discovered that the benefits of using aspirin and NSAIDs like ibuprofen to cut colorectal cancer risk actually hinge on a person’s particular DNA.

“We’ve known for a very long time that NSAIDs and aspirin are protective for colorectal cancer, but they can’t be used as a preventive agent because of the uncertainty of the risk-benefit ratio,” said Dr. Ulrike “Riki” Peters, a cancer prevention researcher at Fred Hutch and senior co-author of the study. “Longtime use can lead to gastrointestinal bleeding and other side effects.”

What researchers didn’t know, however, was why some people seemed to benefit and others did not.

To find out, Peters and her team – including Fred Hutch biostatistician and corresponding co-author Dr. Li Hsu – looked at people’s genes, analyzing data from 10 large population-based studies in the U.S., Canada, Australia and Germany.

The researchers compared genetic and lifestyle data from 8,624 people who developed colorectal cancer with that of 8,553 people who did not (both groups were matched by age and gender) and found some intriguing differences, according to the study published Tuesday in JAMA. 

While regular use of aspirin and NSAIDs was associated with an overall reduced risk of colorectal cancer, there was no such protective effect among about 9 percent of the study participants who carried an uncommon genetic variation on chromosome 15.

And about 4 percent of the participants who carried one or two even rarer alleles on chromosome 12 actually had a higher risk of colorectal cancer with aspirin or NSAID use.

“For these people, NSAIDs and aspirin would not be a benefit,” said Peters. “However, these results need to be replicated in independent studies.”

No blanket recommendations yet

Senior co-author Dr. Andrew Chan, an associate professor of medicine at Harvard Medical School and a gastroenterologist at Massachusetts General Hospital in Boston, said the findings illustrate how difficult it can be to make a blanket recommendation about taking aspirin and NSAIDs to protect against colorectal cancer.

“Ideally, we would love to be able to recommend that everyone take this medication, but I think it’s clear we need to be more personalized in our approach,” he said.  “The message that this study drives home is that medications don’t have the same effects in everyone. It’s important to identify what factors exist that distinguish why some individuals may benefit and some will not.”

Chan said it’s also far too early for people to have genetic testing done to see if they could conceivably benefit from NSAID/aspirin as a preventative against colorectal cancer.

“These findings need to be validated in other populations,” he said. “And even if validated, additional work to translate this into a clinical test is needed. Genetic testing is not just about drawing your blood. It’s about getting the results back and really understanding what they mean.” 

Drs. Ulrike "Riki" Peters and Li Hsu

Dr. Ulrike "Riki" Peters, left, leads an international collaboration of researchers studying the interplay of genes and environment that influence the risk of colorectal cancer. Dr. Li Hsu, right, is the consortium's lead biostatistician.

Photos by Robert Hood / Fred Hutch News Service

Sussing out how lifestyle and genes interact

While the findings are significant, both researchers agree there is still much to know about colorectal cancer risk and the factors that bump it up.

Much of that work is being done by Peters, Hsu and other colleagues through the Genetics and Epidemiology of Colorectal Cancer Consortium, or GECCO, an international collaboration of researchers studying the genetic variants – and environmental factors – that can put someone at risk for colorectal cancer. Fred Hutch is the GECCO coordinating center; Peters is its principal investigator and Hsu, the lead biostatistician.

“Many in the consortium have been interested in the interaction between genetic variants and the environment for a very long time,” said Peters. “It’s the reason we built this consortium. We wanted to start investigating the genetic drivers of common disease. The next step is to ask, ‘Is there something that interacts between the genome and your lifestyle and the environment?’”

In other words, does taking aspirin or exercising regularly or being overweight or eating a lot of red meat (or a lot of fruits and veggies) interact with a person’s own individual DNA to give them a lower or higher risk of colorectal cancer?

“People with different genetic backgrounds, even if they’re exposed to the same thing like NSAID use, will react differently with the same exposure,” said Fred Hutch co-author Hsu, who explained the interplay between genetic variations and environmental or lifestyle factors is a process known as “gene-by-environment interaction.”

“The ultimate goal that everyone wants to get to is a more individually tailored risk prediction and guidance for lifestyle, screening and interventions,” Hsu said. “That’s the ultimate goal but we’re not quite there yet. This is the very first step in that direction.”

Diane Mapes is a staff writer at Fred Hutchinson Cancer Research Center. She has written extensively about health issues for NBC News, TODAY, CNN, MSN, Seattle Magazine and other publications. A breast cancer survivor, she also writes the breast cancer blog doublewhammied.com. Reach her at dmapes@fredhutch.org.

Are you interested in reprinting or republishing this story? Be our guest! We want to help connect people with the information they need. We just ask that you link back to the original article, preserve the author’s byline and refrain from making edits that alter the original context. Questions? Email senior writer/editor Linda Dahlstrom at ldahlstr@fredhutch.org.

Solid tumors, such as those of the colon, are the focus of Solid Tumor Translational Research, a network comprised of Fred Hutchinson Cancer Research Center, UW Medicine and Seattle Cancer Care Alliance. STTR is bridging laboratory sciences and patient care to provide the most precise treatment options for patients with solid tumor cancers.


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