Genetic variation explains why only certain people will benefit from long-term use of anti-inflammatory drugs

“An aspirin a day keeps the doctor away”. Many of us grew up hearing our grandmothers repeat this saying, often regardless of whether we were sick or not. What if this maxim is supported by scientific research? Several studies have shown a link between a low dose of aspirin and a decreased risk of heart attacks and strokes. Taking a low-dose of aspirin each day is also linked to a reduction in the risk of certain cancers, including colorectal cancer. However, these benefits depend on inheriting the ‘right’ version of at least two genes. According to a study from the Fred Hutchinson Cancer Research Center, you can inherit rare genetic changes, which instead increase the risk of colorectal cancer, when aspirin is used regularly.

Aspirin has been around for over 100 years and is a common drug used to treat fever and inflammation. It works by blocking an enzyme called cyclooxygenase, which controls inflammation and blood clotting. Aspirin may be the ‘wonder’ drug because it is cheap and effective, if it was not for the harmful side effects, like the increased risk of intestinal bleeding. Despite such potential side effects, aspirin is recommended by the US Preventative Services Task Force to reduce heart attacks in men from ages 45 – 79, and in women from ages 55 – 79. Heart attacks kill over 600,000 people in the US each year, thus in this scenario, the benefits of taking aspirin outweigh the risk of potential side effects.

There is good evidence that the long-term (5-10 years) use of a low-dose of aspirin will lower the risk of getting colorectal cancer and increase the survival rate in patients with colorectal cancer. Yet, there is also evidence for aspirin having no effect on either colorectal cancer risk or survival in some people. Whether the benefit of reducing the risk of colorectal cancer offsets the harmful effects of aspirin, is a topic that remains controversial. Recent research adds to this debate, revealing genetic variance as another factor that needs further consideration, before deciding whether to use aspirin therapy as a preventative measure against colorectal cancer.

The recent study (Nan et al. 2015) analyzed genetic data from 8,634 colorectal cancer patients and 8,553 healthy individuals – and, like previous studies, found an association between the use of aspirin and the risk of developing colorectal cancer. People who used aspirin or other non-steroidal anti-inflammatory drugs regularly (2-3 days/week) were 30% less likely to develop colorectal cancer.

These researchers were actually going a step further and searching for genetic variation that would influence these positive affects of regular aspirin use. This is exactly what they uncovered – single nucleotide polymorphism (SNP) variation near two genes, MGST1 and IL16, affects the link between aspirin use and cancer risk. The most common nucleotide at each SNP is significantly associated with a decreased risk of colorectal cancer in individuals who used aspirin (or other non-steroidal anti-inflammatory drugs) regularly. The rare form of the SNP near IL16 is not significantly associated with either a decreased or increased risk of cancer. In contrast, inheriting a rare variant of the SNP near MGST1, (about 4% of the study participants), actually increased the risk of developing colorectal cancer when anti-inflammatory drugs were taken. So aspirin therapy can be either beneficial or harmful depending on an individual’s genetics.

No health organization endorses taking aspirin for the sole purpose of preventing cancer, because the decision of who should, and who should not, be taking aspirin as a preventative drug is not an easy one. Many factors like the age of an individual, health complications, potential side effects and now an individual’s genetics need due consideration. Aspirin is one of the most widely used anti-inflammatory drugs in the world and it may be useful against heart attacks. However, in relation to colorectal cancer, whether “an aspirin a day will keep the doctor away” is greatly influenced by something we can test for but can’t change – our genes.