{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T05:01:57Z","timestamp":1789794117254,"version":"4.0.1"},"reference-count":31,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001459","name":"Ministry of Education","doi-asserted-by":"publisher","award":["RS-2025-25441317"],"award-info":[{"award-number":["RS-2025-25441317"]}],"id":[{"id":"10.13039\/501100001459","id-type":"DOI","asserted-by":"publisher"}]},{"award":["RS-2025-25441317"],"award-info":[{"award-number":["RS-2025-25441317"]}],"id":[{"id":"https:\/\/ror.org\/01p262204","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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 \u00b1 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\u20131.35), 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\u20131.92) and concurrent CC and NNTP use (aHR 1.23, 95% CI 1.04\u20131.45). 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.<\/jats:p>","DOI":"10.3390\/cancers18183010","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T16:07:29Z","timestamp":1789574849000},"page":"3010","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Smoking Status, Including Non-Combustible Nicotine or Tobacco Products Use, and Site-Specific Colorectal Cancer Risk: A Nationwide Cohort Study"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6774-6112","authenticated-orcid":false,"given":"Seonghye","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Family Medicine & Supportive Care Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 06351, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae-Se","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 06351, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8128-8920","authenticated-orcid":false,"given":"Dong Wook","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Family Medicine & Supportive Care Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 06351, Republic of Korea"},{"name":"Department of Clinical Research Design and Evaluation, Samsung Advanced Institute for Health Science and Technology (SAIHST), Sungkyunkwan University, 50 Irwon-dong, Gangnam-gu, Seoul 06351, Republic of Korea"},{"name":"Department of Digital Health, Samsung Advanced Institute for Health Science and Technology (SAIHST), Sungkyunkwan University, 50 Irwon-dong, Gangnam-gu, Seoul 06351, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyungdo","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Statistics and Actuarial Science, Soongsil University, 369 Sangdo-ro, Dongjak-gu, Seoul 06978, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byung-Hoon","family":"Min","sequence":"additional","affiliation":[{"name":"Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 06351, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1097\/CEJ.0000000000000011","article-title":"Meta-analysis of prospective cohort studies of cigarette smoking and the incidence of colon and rectal cancers","volume":"24","author":"Cheng","year":"2015","journal-title":"Eur. J. Cancer Prev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"113179","DOI":"10.1016\/j.fct.2022.113179","article-title":"Carcinogenic components of tobacco and tobacco smoke: A 2022 update","volume":"165","author":"Li","year":"2022","journal-title":"Food Chem. Toxicol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1093\/aje\/kwaa005","article-title":"Smoking-Related Risks of Colorectal Cancer by Anatomical Subsite and Sex","volume":"189","author":"Gram","year":"2020","journal-title":"Am. J. Epidemiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e2340859","DOI":"10.1001\/jamanetworkopen.2023.40859","article-title":"E-Cigarette Use Among US Adults in the 2021 Behavioral Risk Factor Surveillance System Survey","volume":"6","author":"Erhabor","year":"2023","journal-title":"JAMA Netw. Open"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1146\/annurev-pharmtox-042921-084202","article-title":"E-Cigarette Toxicology","volume":"62","author":"Gordon","year":"2022","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_6","first-page":"6","article-title":"Evidence update on the cancer risk of vaping e-cigarettes: A systematic review","volume":"23","author":"Kundu","year":"2025","journal-title":"Tob. Induc. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1136\/gutjnl-2020-321534","article-title":"Genetic architectures of proximal and distal colorectal cancer are partly distinct","volume":"70","author":"Huyghe","year":"2021","journal-title":"Gut"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2765","DOI":"10.1001\/jama.2008.839","article-title":"Smoking and colorectal cancer: A meta-analysis","volume":"300","author":"Botteri","year":"2008","journal-title":"JAMA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.cgh.2010.10.012","article-title":"Cigarette smoking and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition study","volume":"9","author":"Leufkens","year":"2011","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1186\/s12967-021-02815-4","article-title":"Association between cigarette smoking and colorectal cancer sidedness: A multi-center big-data platform-based analysis","volume":"19","author":"Yang","year":"2021","journal-title":"J. Transl. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1001\/jamainternmed.2015.7110","article-title":"Korean national health insurance database","volume":"176","author":"Shin","year":"2016","journal-title":"JAMA Intern. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e016640","DOI":"10.1136\/bmjopen-2017-016640","article-title":"Cohort profile: The national health insurance service-national health screening cohort (NHIS-HEALS) in Korea","volume":"7","author":"Seong","year":"2017","journal-title":"BMJ Open"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e111","DOI":"10.3346\/jkms.2025.40.e111","article-title":"Leveraging National Health Insurance Service Data for Public Health Research in Korea: Structure, Applications, and Future Directions","volume":"40","author":"Lim","year":"2025","journal-title":"J. Korean Med. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"keaf451","DOI":"10.1093\/rheumatology\/keaf451","article-title":"RA and risk of colorectal cancer: A nationwide cohort study","volume":"65","author":"Jeon","year":"2025","journal-title":"Rheumatology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"30","DOI":"10.2188\/jea.JE20230310","article-title":"Income dynamics and risk of colorectal cancer in individuals with type 2 diabetes: A nationwide population-based cohort study","volume":"35","author":"Park","year":"2025","journal-title":"J. Epidemiol."},{"key":"ref_16","unstructured":"Centers for Disease Control and Prevention, and National Center for Health Statistics (2026, September 06). National Health Interview Survey: Adult Tobacco Use\u2014Glossary, Available online: https:\/\/archive.cdc.gov\/www_cdc_gov\/nchs\/nhis\/tobacco\/tobacco_glossary.htm."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"66","DOI":"10.18332\/tid\/125232","article-title":"Prevalence and correlates of current use of heated tobacco products among a nationally representative sample of Korean adults: Results from a cross-sectional study","volume":"18","author":"Kim","year":"2020","journal-title":"Tob. Induc. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"352","DOI":"10.4143\/crt.2021.044","article-title":"Validation of cancer diagnosis based on the national health insurance service database versus the national cancer registry database in Korea","volume":"54","author":"Yang","year":"2022","journal-title":"Cancer Res. Treat. Off. J. Korean Cancer Assoc."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"312","DOI":"10.3961\/jpmph.23.033","article-title":"Operational definitions of colorectal cancer in the Korean National Health Insurance Database","volume":"56","author":"Park","year":"2023","journal-title":"J. Prev. Med. Public Health"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"9","DOI":"10.23838\/pfm.2021.00135","article-title":"National General Health Screening Program in Korea: History, current status, and future direction","volume":"6","author":"Shin","year":"2022","journal-title":"Precis. Future Med."},{"key":"ref_21","unstructured":"World Health Organization (2000). The Asia-Pacific Perspective: Redefining Obesity and Its Treatment, World Health Organization."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: A practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R. Stat. Soc. Ser. B (Methodol.)"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1093\/jnci\/djm176","article-title":"Association between cigarette smoking and colorectal cancer in the Women\u2019s Health Initiative","volume":"99","author":"Paskett","year":"2007","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1940","DOI":"10.14309\/ajg.0000000000000803","article-title":"Smoking and Colorectal Cancer Risk, Overall and by Molecular Subtypes: A Meta-Analysis","volume":"115","author":"Botteri","year":"2020","journal-title":"Am. J. Gastroenterol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1038\/s41416-020-0803-0","article-title":"Smoking, alcohol consumption and colorectal cancer risk by molecular pathological subtypes and pathways","volume":"122","author":"Amitay","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.semcancer.2019.01.001","article-title":"Overview of the oncogenic signaling pathways in colorectal cancer: Mechanistic insights","volume":"58","author":"Farooqi","year":"2019","journal-title":"Semin. Cancer Biol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Jin, M., Shang, F., Wu, J., Fan, Q., Chen, C., Fan, J., Liu, L., Nie, X., Zhang, T., and Cai, K. (2021). Tumor-Associated Microbiota in Proximal and Distal Colorectal Cancer and Their Relationships with Clinical Outcomes. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.727937"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.suc.2009.09.001","article-title":"Anorectal anatomy and physiology","volume":"90","author":"Barleben","year":"2010","journal-title":"Surg. Clin. North. Am."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"167667","DOI":"10.1016\/j.scitotenv.2023.167667","article-title":"The impact of toxic metal bioaccumulation on colorectal cancer: Unravelling the unexplored connection","volume":"906","author":"Bonfiglio","year":"2024","journal-title":"Sci. Total Environ."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Ganapathy, V., Manyanga, J., Brame, L., McGuire, D., Sadhasivam, B., Floyd, E., Rubenstein, D.A., Ramachandran, I., Wagener, T., and Queimado, L. (2017). Electronic cigarette aerosols suppress cellular antioxidant defenses and induce significant oxidative DNA damage. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0177780"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1007\/s00204-024-03932-x","article-title":"E-cigarettes increase the risk of adenoma formation in murine colorectal cancer model","volume":"99","author":"Sayed","year":"2025","journal-title":"Arch. Toxicol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/18\/3010\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T04:16:01Z","timestamp":1789791361000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/18\/3010"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,16]]},"references-count":31,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["cancers18183010"],"URL":"https:\/\/doi.org\/10.3390\/cancers18183010","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,16]]}}}