Impact of long-term N-acetylcysteine use on cancer risk

Chronic obstructive pulmonary disease (COPD) patients face an increased risk of developing various malignancies due to shared risk factors and underlying systemic inflammation. N-acetylcysteine (NAC) has shown potential anticancer properties in preclinical studies, but clinical evidence in COPD patients is limited. We conducted a nationwide propensity score-matched cohort study using data from Taiwan's National Health Insurance Research Database to evaluate the anticancer effects of NAC in COPD patients. Patients diagnosed with COPD between 2008 and 2019 were included, and those with pre-existing cancer were excluded. NAC use was defined as consistent administration for most days with an average dose exceeding 28 cumulative defined daily doses (cDDDs) annually. Cox regression models were adjusted for various covariates was employed. PSM yielded 91,546 patients, evenly distributed between NAC and non-NAC groups. Multivariate Cox regression analysis revealed a lower cancer risk in patients with long-term NAC use compared to non-users (adjusted hazard ratio [aHR] 0.69, 95% confidence interval [CI] 0.66-0.72; P<0.001). Dose-dependent relationships were observed, with higher daily NAC intake associated with reduced cancer risk. Time-varying Cox regression analysis demonstrated significant reductions in the risk of specific cancers, including hepatocellular carcinoma, colorectal cancer, and breast cancer, among NAC users compared to non-users. Our study provides clinical evidence supporting the potential anticancer effects of NAC in COPD patients. These findings highlight the importance of exploring NAC as a chemopreventive agent in high-risk populations and inform clinical practice and future research endeavors.