Chronic Opioid Use and Risk of Cancer in Patients with Chronic Noncancer Pain: A Nationwide Historical Cohort Study

Background: To investigate whether chronic opioid therapy is associated with a higher risk of cancer among noncancer patients with chronic pain. Methods: A population-based historical cohort study of the South Korean adult population was conducted using data from the National Health Insurance Service. We included patients registered with a diagnostic code of M00-M99 (musculoskeletal system and connective tissue diseases) according to the International Classification of Diseases, 10th revision, in 2010. Patients prescribed a continuous supply of any opioid drug for >= 90 days were defined as chronic opioid users. Results: A total of 351,701 patients were analyzed. Among them, 25,153 (7.2%) were chronic opioid users. Using a multivariate time-dependent Cox regression model, the risk of cancer in chronic opioid users was 1.20-fold higher than that in controls [HR, 1.20; 95% confidence interval (CI), 1.15-1.25; P < 0.001]. On subgroup analysis according to opioid potency, the cancer risk in chronic weak and strong opioid users was 1.18-fold (HR, 1.18; 95% CI, 1.13-1.23; P < 0.001) and 1.32-fold (HR, 1.32; 95% CI, 1.10-1.59; P = 0.003) higher than that in controls, respectively. Conclusions: Chronic opioid therapy was associated with an increased risk of cancer among noncancer patients with chronic pain. This association was more evident in chronic strong opioid users. However, as unmeasured and potential confounders may have affected the results, the relationship between chronic opioid use and cancer risk should be evaluated with caution. Impact: Chronic opioid therapy was associated with an increased risk of cancer among noncancer patients.