For most people, a regular dose of aspirin, Advil, Aleve or certain other over-the-counter painkillers can reduce the risk of colorectal cancer by about one-third. But for some people, these same pills make colorectal cancer more likely.
Now researchers have figured out a way to tell these two groups apart by looking at three specific spots in the vast human genome.
After combing through the DNA of more than 17,000 people in four countries, the researchers identified a few genetic variants that appear to influence whether drugs like aspirin increase or decrease one’s risk of colorectal cancer. Their findings were published Tuesday by the Journal of the American Medical Assn.
The study is an example of how “big science” can untangle the influence of genetics and the environment and show how the two interact to cause – or prevent – diseases, according to Dr. Richard C. Wender, the chief cancer control officer for the American Cancer Society in Atlanta.
“The ability to translate genetic profiling into tailored preventive care plans for individuals is still years away,” Wender wrote in an editorial that accompanies the JAMA report. But the analysis gives scientists a clearer picture of how to get there from here, he added.
Lots of research had already linked nonsteroidal anti-inflammatory drugs – the painkillers better known as NSAIDs – with a reduced risk of the colorectal growths that can lead to cancer. But doctors aren’t sure why this is, and they’ve been reluctant to use NSAIDs for cancer prevention without a better understanding of why the drugs seem to work.
So an international group of researchers mined data from 10 long-term studies that tracked people who were diagnosed with colorectal cancer, along with healthy volunteers who were matched according to age, gender and other demographic factors. All of the volunteers answered questions about their use of NSAIDs (including aspirin, ibuprofen and naproxen) and DNA samples to researchers.
The human genome contains about 3 billion base pairs of the DNA letters A (adenine), T (thymine), G (guanine) and C (cytosine). In some places along the genome, there are spots where some people have one particular letter and others have another. The researchers included about 2.7 million of these places – which are called single nucleotide polymorphisms, or SNPs – in their analysis.
After crunching a ton of data, the researchers identified three intriguing SNPs. When people had the common versions of these SNPs, taking the painkillers was associated with a 34% reduced risk of colorectal cancer. But when people had uncommon versions of these SNPs, taking the drugs offered no benefit – or else increased the risk of colorectal cancer.
The first of these SNPs is known as rs2965667, and it sits on chromosome 12. In the study, 96% of the volunteers had two copies of “T” at that location. Among the 4% of people who had other combinations of letters there, those who took aspirin and/or NSAIDs were almost twice as likely to be diagnosed with colorectal cancer compared with those who didn’t.
The story was nearly the same with a second SNP, rs10505806, which is also located on chromosome 12. In the study, 95% of people had two copies of “A” in that location. For the other 5%, those who took the painkillers were 56% more likely to get colorectal cancer than those who didn’t.
The third relevant SNP was rs16973225, on chromosome 15, and 91% of the study participants had two “A” copies in that location. While this group saw an upside by taking aspirin and NSAIDs, the other 9% had the same colorectal cancer risk regardless of whether they took the painkillers.
The locations of these SNPs give researchers some clues about how the painkillers might be fighting colorectal cancer, the study authors wrote. For instance, they named several genes near the SNPs that are thought to play a role in other kinds of cancers, or that promote the kind of inflammation that can lead to colorectal cancer.
About 136,830 Americans were diagnosed with colorectal cancer in 2014, and 50,310 died of the disease, according to the National Cancer Institute.