INTRODUCTION:Preclinical evidence suggests that melatonin may affect cellular pathways involved in colorectal cancer (CRC). We sought to test whether melatonin use was associated with decreased risk of CRC using population-based data.METHODS:We performed a nationwide cohort study using a new-user study design. We identified a total of 58,657 incident melatonin users aged 50 years and older from the Prescribed Drug Register, and matched them with 175,971 comparisons who did not use melatonin, on the ratio of 1:3. The Cox regression model was used to calculate hazard ratios and 95% confidence intervals.RESULTS:The incidence rate of CRC was 10.40 per 10,000 person-years for melatonin users, whereas the rate was 12.82 per 10,000 person-years in the nonusers. We found a significant negative association between melatonin use and risk of CRC (adjusted hazard ratio, 0.82; 95% confidence interval, 0.72-0.92). A test for trend showed a significant dose-response correlation (P < 0.001). The decrease of CRC risk was independent of tumor location and stage at diagnosis. When stratified by age groups, the inverse association was significant only among individuals aged 60 years and older.DISCUSSION:This population-based cohort study suggests that the use of melatonin was associated with a reduced risk of CRC. Further studies are needed to confirm the observed association and to explore the underlying mechanisms.