Use of Selective Serotonin Reuptake Inhibitors Is Associated with a Lower Risk of Colorectal Cancer among People with Family History

SIMPLE SUMMARY: Individuals with a family history of colorectal cancer (CRC) are at a high risk of developing CRC. We performed a nationwide cohort study to explore whether selective serotonin reuptake inhibitors (SSRIs) play a role in preventing CRC among individuals with family history. This report suggests that SSRI use was associated with a reduced incidence of CRC among people with a family history of CRC, and the decreased risk of CRC showed a non-linear, dose-dependent pattern. In addition, we found that the use of SSRIs was strongly associated with CRC diagnosed at an advanced stage rather than at an earlier stage, suggesting that the SSRIs might reduce the metastatic potential of cancer cells leading to stage migration. This population-based cohort study suggests that the use of SSRIs is associated with a reduced risk of CRC among individuals with a family history of CRC. ABSTRACT: Individuals with a family history of colorectal cancer (CRC) are at a high risk of developing CRC. Preclinical and population-based evidence suggests that selective serotonin reuptake inhibitors (SSRIs) might play a role in preventing CRC. We performed a nationwide cohort study to explore whether the use of SSRIs could reduce CRC risk among individuals with family history. We identified individuals aged 50 and above who had one or more first-degree relatives diagnosed with CRC. A total of 38,617 incident SSRI users were identified and matched with 115,851 non-users, on a ratio of 1:3. The Cox regression model was used to calculate hazard ratios (HRs) and 95% CI confidence intervals (CIs). We found a significant negative association between SSRI use and the risk of CRC (adjusted HR, 0.77; 95% CI, 0.70–0.85). Restricted cubic spline regression showed a non-linear dose-responded relationship between SSRI use and CRC risk. The association was stronger in rectal cancer than colon cancer (adjusted HR, 0.73 vs. 0.79), and more pronounced in advanced-stage CRC than early-stage CRC (adjusted HR, 0.73 vs. 0.80). This population-based cohort study suggests that the use of SSRIs is associated with a reduced risk of CRC among individuals with a family history of CRC.