Use of aspirin and selective serotonin reuptake inhibitors (SSRIs), as either monotherapy or combined, is associated with a lower risk for colorectal cancer (CRC), according to a study in the American Journal of Gastroenterology.

Investigators conducted a nested case-control study of 24,786 patients diagnosed with CRC between January 1, 2007, and March 31, 2014 included in Swedish registers. Each confirmed CRC case was randomly matched with 3 control individuals.

Among both the cases and controls, 51.9% were male, 34.9% had an age at index >75 years, and 33% had an age at index of ≤65 years. After an average of 7.1 years of follow-up for the case group, the incidence rate of CRC was 4.34 per 10,000 person-years.


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Overall aspirin use was inversely associated with CRC risk (adjusted odds ratio [OR], 0.91; 95% CI, 0.87-0.96). The overall use of SSRIs was also negatively associated with CRC risk (adjusted OR, 0.91; 95% CI, 0.85-0.97).

Aspirin monotherapy, SSRI monotherapy, and combined use of aspirin and SSRIs had adjusted ORs for CRC of 0.91 (95% CI, 0.87-0.97), 0.93 (95% CI, 0.86-1.00), and 0.77 (95% CI, 0.67-0.89), respectively, compared with nonusers. The researchers found a significant interaction at the additive scale with a relative excess risk for interaction of –0.07 (P <.001), and no interaction was observed on the interactive scale.

Aspirin monotherapy was also significantly associated with a reduced risk for proximal colon cancer (adjusted OR, 0.89; 95% CI, 0.81-0.97) and rectal cancer (adjusted OR, 0.88; 95% CI, 0.80-0.97). SSRI monotherapy was only negatively associated with a risk for rectal cancer. The combined use of aspirin and SSRIs was significantly associated with a lower risk for distal colon cancer (adjusted OR, 0.71; 95% CI, 0.55-0.93).

In a sensitivity analysis that excluded participants who had less than 3 years of follow-up, the combined use of aspirin and SSRIs was associated with a reduced risk for CRC (adjusted OR, 0.77; 95% CI, 0.67-0.89).

The study authors noted that their results might be affected by protopathic bias, as aspirin and SSRIs could have been initiated in response to the first symptoms of the disease, which had been undiagnosed at that point. Additionally, potential causes for CRC, such as smoking and dietary factors, were not adjusted due to the lack of information in the databases.

“The significant interaction at the additive scale further supported our hypothesis that combined aspirin and SSRI might have a synergistic effect against the development of CRC,” the investigators commented. “The observed relationship showed a dose-dependent pattern hence providing biological plausibility,” they concluded.

Reference

Zhang N, Sundquist J, Sundquist K, et al. Combined use of aspirin and selective serotonin reuptake inhibitors is associated with lower risk of colorectal cancer: a nested case-control study. Am J Gastroenterol. 2021;116(6):1313-1321. doi: 10.14309/ajg.0000000000001192.