NSAID Use May Decrease Colorectal Cancer Risk in Certain Molecular Subtypes

Regular, frequent use of nonsteroidal anti-inflammatory drugs (NSAIDS) like aspirin could reduce an individual’s colorectal cancer risk — especially if the person harbors certain genetic conditions – according to recent research conducted at the German Cancer Research Center.

“Increased knowledge of the associations between NSAID use and (colorectal cancer) risk by molecular subtypes may contribute to better understanding of the etiologic mechanisms by which NSAIDs lower (colorectal cancer) risk and help shed more light on the various carcinogenic processes,” the researchers wrote in their study, which was published in the Journal of National Cancer Institute.

The researchers analyzed 2,444 cases of newly diagnosed colorectal cancer compared with 3,130 healthy control patients to determine if NSAID use affected colorectal cancer risk. They then compared results by molecular subtype, including those with tumors that are microsatellite stable (MSS) or microsatellite instable (MSI), tumors with CpG island methylator phenotype (CIMP) and BRAF- or KRAS-positive tumors.

They explained that, while colorectal cancer is often seen as one disease, it is extremely heterogenous in its features and molecular pathways — hence the importance to break out their study by these different molecular pathways.

Study participants filled out a self-administered questionnaire that asked them to categorize their NSAID use in one of three ways:

• current: regular use up to the time of diagnosis or beginning of symptoms that led to diagnosis (for those with cancer) or interview (for those without);
• ever: regular use at any time, past and current; or
• never: no period of regular use.

Regular use was defined as, “a usage pattern of two or more times per week for at least one year.”

Ultimately, regular NSAID use was associated with lower colorectal cancer risk in people whose tumors were MSS, BRAF wildtype, meaning a gene when it is found in its natural, non-mutated form, or KRAS wildtype. The association between NSAID use and MSI-high, BRAF- or KRAS-mutant positive colorectal cancer was not so clear and did not reach statistical significance. However, for patients whose tumors were MSI-high and did not have BRAF or KRAS mutations, there was a much stronger association in risk reduction observed.

A 2016 recommendation from the US Preventive Services Task Force (USPSTF) encouraged adults between the ages of 50 and 59 to start regular use of low-dose aspirin to reduce risk of cardiovascular disease and colorectal cancer. However, the researchers noted their findings do not support regular NSAID use in the primary prevention for KRAS-mutant or MSI-high colorectal cancer.

These findings, they added, could be a jumping-off point for future studies to better understand the relationship between NSAIDs, colorectal cancer and the differences in molecular makeup within the disease.

“Although this area of research is still at an exploratory stage, examining the effect of regular use of NSAIDs by molecular pathological subtype may, on one hand, shed light on the molecular pathogenesis of colorectal cancer and, on the other hand, help enhance our understanding of the mechanisms through which NSAIDs reduce colorectal cancer risk,” the researchers wrote, adding that their findings warrant the need for other large studies on this topic.