Combined Use of Aspirin and Selective Serotonin Reuptake Inhibitors Is Associated With Lower Risk of Colorectal Cancer: A Nested Case-Control Study

Abstract

INTRODUCTION: Chemoprevention against colorectal cancer (CRC) is greatly needed. As the development of CRC involves multiple dysfunctional pathways, it is thus reasonable to combine some agents that address several pathways to achieve better chemoprotection. We aimed to explore whether the use of aspirin and selective serotonin reuptake inhibitors (SSRIs)—either as monotherapy or combined—can have a clinical benefit against CRC. METHODS: We performed a nested case-control study using nationwide Swedish registers. We recruited 24,786 CRC cases and randomly matched to 74,358 controls conditional on birth year and sex using incidence-density sampling. The conditional logistic regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Additive interaction was calculated as the relative excess risk for interaction, and multiplicative interaction was calculated by including a product term in the regression model. RESULTS: Both aspirin and SSRIs monotherapy were negatively associated with CRC risk, but the combined use of aspirin and SSRIs was associated with an even lower CRC risk (adjusted OR, 0.77, 95% CI, 0.67–0.89) than aspirin monotherapy (adjusted OR, 0.91, 95% CI, 0.87–0.97) or SSRI monotherapy (adjusted OR, 0.93, 95% CI, 0.86–1.00). A significant interaction was observed at the additive scale with a relative excess risk for interaction of −0.07 (P < 0.001), whereas no interaction was noted on the interactive scale. The inverse associations of CRC with aspirin and SSRIs showed a dose-dependent pattern. DISCUSSION: This study suggests that the use of aspirin and SSRIs—either as monotherapy or combined—was associated with a reduced risk of CRC. The stronger chemoprevention of combined use of aspirin and SSRIs is innovative and calls for further studies to confirm the underlying mechanisms and the plausibility of clinical recommendation.

NSAIDs: Old Acquaintance in the Pipeline for Cancer Treatment and Prevention─Structural Modulation, Mechanisms of Action, and Bright Future

“…Several epidemiological and clinical studies supported the potential benefits of NSAIDs in the prevention and treatment of several cancers, including colon, ,, ovarian, breast, , lung, and prostate . In this context, long-term use of aspirin reduces the risk of colorectal, ,− ovarian, , breast, and prostate cancer and hepatocellular carcinoma. , Further, almost 90 clinical trials involving aspirin are being or have been carried out, such as the randomized phase II trial that demonstrated aspirin’s pharmacological efficacy in preventing colorectal cancer in patients at increased risk of colorectal cancer . Thus, the U.S. Preventive Services Task Force (USPSTF) recommended that aspirin can be used to help reduce the risk of cancers including colorectal cancer, although the long-term use of aspirin in older individuals is still being discussed , and needs further confirmation.…”

SSRI antidepressant citalopram reverses the Warburg effect to inhibit hepatocellular carcinoma by directly targeting GLUT1

“…Accumulating epidemiological studies reveal that SSRIs use has a lower risk of death from various cancer types, such as liver cancer, bladder cancer, kidney cancer, breast cancer, endometrial cancer, and ovarian cancer [6][7][8][9][10][11] . Recently, our group also showed that SSRIs monotherapy was inversely associated with colorectal cancer risk, and the combined use of aspirin and SSRIs showed a synergistic effect 12 . Consistent with clinical observations, data from in vitro cell experiments and preclinical models suggest that SSRIs exert substantial anti-tumor effects, including but not limited to cell senescence, cell apoptosis, invasive potential, and drug resistance [13][14][15][16] .…”

Complex Effects of Sertraline and Citalopram on In Vitro Murine Breast Cancer Proliferation and on In Vivo Progression and Anxiety Level

“…In another study, however, high doses of sertraline did not improve mood symptoms, wellbeing, or survival of patients with advanced-stage cancer but without major depression [ 19 ]. Notably, several epidemiological studies have shown that chronic use of SSRIs can lower the risk of developing some types of cancer [ 20 , 21 , 22 , 23 ].…”