{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T06:33:16Z","timestamp":1773815596944,"version":"3.50.1"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cancer remains a major global health burden, with 10 million deaths in 2020 and among the 35 million adults worldwide with psychoactive substance use disorders (SUDs), it is a major contributor to premature mortality. In the U.S., tobacco causes over 30% of cancer deaths and alcohol nearly 5%, highlighting the role of modifiable behaviors. Despite this clinical and economic burden, national long-term data on co-occurring SUDs and cancer mortality remain limited. We therefore analyzed 22 years (1999\u20132020) of U.S. mortality data from CDC WONDER (Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research) to evaluate temporal trends and demographic and geographic disparities in psychoactive substance\u2013related mental disorder mortality in relation to cancer among adults aged \u226525 years.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Mortality data for adults aged \u226525 were obtained from CDC WONDER using ICD-10 codes C00\u2013D48 (cancer) and F10\u2013F19 (psychoactive substance\u2013related mental disorders). We calculated age-adjusted mortality rates (AAMRs) and annual percent changes (APCs) by demographics and region. Subgroup analyses paired cancer deaths with alcohol, tobacco, and other psychoactive substance categories to assess substance-specific trends.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      From 1999\u20132020, 1,789,591 deaths involved both cancer and substance use (SU)\u2013related mental disorders. Overall AAMR rose from 5.66 in 1999 to 43.26 in 2020, increasing sharply from 1999\u20132005 (APC: 41.67), more gradually through 2012 (APC: 4.36), and stabilizing thereafter (APC: \u20131.23; p&amp;gt;0.05). Rates were higher in males than females (51.57\n                      <jats:italic>vs<\/jats:italic>\n                      . 25.8), highest in non-Hispanic (NH) American Indian\/Alaska Native individuals, and lowest in NH Asian\/Pacific Islanders. Regionally, AAMR was greatest in the Midwest (49.32) and lowest in the West (25.38) with Vermont and California representing the highest and lowest AAMR states, respectively. Nonmetropolitan areas had higher rates than metropolitan areas (49.6\n                      <jats:italic>vs<\/jats:italic>\n                      . 34.26). By substance, alcohol-related AAMR declined until 2012 then rose, tobacco increased sharply early and later stabilized, and \u201cpsychoactive drug\u201d\u2013related mortality was stable until 2008 before increasing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Overall, AAMR plateaued after 2012, with the highest burden in NH American Indian\/Alaska Natives, males, and rural Midwest residents, highlighting demographic and geographic disparities among individuals with concomitant cancer and psychoactive substance use\u2013related mental disorders.<\/jats:p>\n                  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Pakistan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aizaz Anwar","family":"Khalid","sequence":"additional","affiliation":[{"name":"Department of Medicine, Peshawar Medical College","place":["Peshawar, Pakistan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aisha","family":"Chaudhary","sequence":"additional","affiliation":[{"name":"Department of Medicine, Fazaia Medical College","place":["Islamabad, Pakistan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saqib Raza","family":"Khan","sequence":"additional","affiliation":[{"name":"Verspeeten Family Cancer Centre, London Health Sciences Centre","place":["London, ON, Canada"]},{"name":"Department of Oncology, Division of Medical Oncology, Schulich School of Medicine and Dentistry, Western University","place":["London, ON, Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed Hammad 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