Smoking Status, Including Non-Combustible Nicotine or Tobacco Products Use, and Site-Specific Colorectal Cancer Risk: A Nationwide Cohort Study

Purpose: Cigarette smoking is an established risk factor for colorectal cancer (CRC), yet the association between smoking status, including non-combustible nicotine or tobacco product (NNTP) use, and site-specific CRC risk remains unclear. Methods: This population-based retrospective cohort study used data from 4,489,451 participants in the Korean National Health Insurance System database. Smoking status was classified according to combustible cigarette (CC) and NNTP use. Multivariable Cox regression models were used to estimate adjusted hazard ratios (aHRs) for CRC risk. Results: During a mean follow-up of 3.4 ± 0.4 years, 17,538 incident CRC cases occurred. Compared with never smoking, exclusive CC use was associated with the highest CRC risk (aHR 1.29, 95% CI 1.23–1.35), with elevated risks across the colon, rectum, distal colon, and unspecified sites. Rectal cancer risk was higher for switching from CCs to NNTPs (aHR 1.51, 95% CI 1.19–1.92) and concurrent CC and NNTP use (aHR 1.23, 95% CI 1.04–1.45). Compared with exclusive CC use, all other smoking-status groups had lower CRC risks, with subsite variations. Colon cancer risk was lower for switching from CCs to NNTPs and concurrent CC and NNTP use; rectal cancer risk was lowest for exclusive NNTP use; and distal colon cancer risk was lowest for concurrent CC and NNTP use. Stratified analyses showed significant interactions of smoking status with age and alcohol consumption in relation to CRC incidence. Conclusions: CRC risk varied by smoking status and anatomical subsite. Further studies are needed to clarify the long-term effects of NNTP use on CRC risk.