Mao JH, Chang H. From residue to cancer risk: How thirdhand smoke drives cancer hallmarks. World J Clin Oncol 2026; 17(6): 121469 [DOI: 10.5306/wjco.121469]
Corresponding Author of This Article
Hang Chang, PhD, Principal Investigator, Division of Biological Systems and Engineering, Berkeley Biomedical Data Science Center, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, United States. hchang@lbl.gov
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Public, Environmental & Occupational Health
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review-article
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Mao JH, Chang H. From residue to cancer risk: How thirdhand smoke drives cancer hallmarks. World J Clin Oncol 2026; 17(6): 121469 [DOI: 10.5306/wjco.121469]
World J Clin Oncol. Jun 24, 2026; 17(6): 121469 Published online Jun 24, 2026. doi: 10.5306/wjco.121469
From residue to cancer risk: How thirdhand smoke drives cancer hallmarks
Jian-Hua Mao, Hang Chang
Jian-Hua Mao, Hang Chang, Division of Biological Systems and Engineering, Berkeley Biomedical Data Science Center, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, United States
Author contributions: Mao JH and Chang H planed the outline of the manuscript, wrote and edited the manuscript; all authors have read and approved the final manuscript.
AI contribution statement: After drafting this minireview, the authors used ChatGPT to refine the language and readability. The authors discussed the reviewers’ comment and together wrote the responses to these comments. Then we used ChatGPT to polish English. All original content was provided by the authors, who reviewed and edited the AI’s suggestions before final adoption. The authors take full responsibility for the content of the publication.
Supported by the University of California Tobacco Related Disease Research Program (UC TRDRP), No. T32PT6221.
Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.
Corresponding author: Hang Chang, PhD, Principal Investigator, Division of Biological Systems and Engineering, Berkeley Biomedical Data Science Center, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, United States. hchang@lbl.gov
Received: March 25, 2026 Revised: April 13, 2026 Accepted: June 2, 2026 Published online: June 24, 2026 Processing time: 89 Days and 14.5 Hours
Abstract
Thirdhand smoke (THS) is a reservoir of toxic compounds that persist in indoor environments and on surfaces long after active smoking has ceased. Major THS chemicals, including nicotine, tobacco-specific nitrosamines, polycyclic aromatic hydrocarbons, and heavy metals, can induce DNA damage, epigenetic alterations, oxidative stress, and chronic inflammation. These biological changes contribute to one or more canonical hallmarks of cancer. In this minireview, we propose an integrated mechanistic framework that incorporates the hallmarks of cancer into environmental exposure risk assessment. This framework offers a system-level approach to carcinogenicity assessment that transcends the limitations of conventional single-endpoint toxicological assays. As a case application, we systematically analyze how THS chemicals disrupt specific cancer hallmarks and delineate the molecular and cellular mechanisms through which persistent tobacco smoke residues promote carcinogenesis. These insights establish a mechanistically grounded framework for assessing the environmental cancer hazard associated with THS.
Core Tip: Thirdhand smoke (THS) represents a persistent and underrecognized environmental carcinogen whose complex chemical mixture drives cancer-relevant biological processes beyond the window of active smoking. By integrating THS-induced molecular and cellular perturbations, such as DNA damage, epigenetic reprogramming, oxidative stress, and chronic inflammation, within the framework of the hallmarks of cancer, a systems-level paradigm for carcinogenic risk assessment emerges. This approach moves beyond traditional single-endpoint toxicology to capture the cumulative, multi-pathway impact of chronic low-dose exposures. Applying this framework to THS reveals how residual tobacco toxicants synergistically disrupt multiple cancer hallmarks, providing a mechanistically grounded basis for evaluating long-term cancer risk and informing environmental health policy.
