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Annual Review of Cancer Biology

Volume 9, 2025

Not All Carcinogens Are Directly Mutagenic: A Holistic View of the Environmental Exposure–Cancer Connection

  • Derick Okwan-Duodu1, Arun R. Pandiri2 and David J. Adams3
  • 1Department of Pathology, Stanford University School of Medicine, Stanford, California, USA 2Comparative and Molecular Pathogenesis Branch, Division of Translational Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA 3Experimental Cancer Genetics, Wellcome Sanger Institute, Cambridge, United Kingdom; email: [email protected]
  • Vol. 9:21-41 (Volume publication date April 2025)
  • First published as a Review in Advance on October 31, 2024
  •  
    This work is licensed under a Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See credit lines of images or other third-party material in this article for license information.

Abstract

Cancers, a leading cause of morbidity and mortality worldwide, are undergoing notable shifts in incidence patterns. Cancer subtypes generally associated with advancing age are now increasingly being diagnosed in younger populations, while gender disparities in cancer susceptibility have fluctuated across various malignancies. Some cancer subtypes previously confined to specific geographical populations are now globally prevalent. Remarkably, these changing patterns of cancer incidence have occurred despite relatively stable mutational landscapes specific to each cancer type, highlighting the role of environmental exposures (exposomes) as potential drivers of these trends. Intriguingly, evidence suggests that the exposome may exert some of its influence through nonmutagenic mechanisms, although the precise ways in which environmental carcinogens trigger or promote cancer development remain poorly understood. This review summarizes the current understanding of the mutagenic and nonmutagenic mechanisms through which carcinogens, including tobacco smoke, air pollutants, metals, diet, and alcohol, impact cancer development, as this may help inform precision prevention and public health policy.

Keyword(s): cancer incidence, cancer promotion, carcinogens, driver mutations, environmental exposures, mutagens
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2025-04-11
2025-06-15
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/content/journals/10.1146/annurev-cancerbio-060424-052905
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Not All Carcinogens Are Directly Mutagenic: A Holistic View of the Environmental Exposure–Cancer Connection
Annual Review of Cancer Biology 9, 21 (2025); https://doi.org/10.1146/annurev-cancerbio-060424-052905
/content/journals/10.1146/annurev-cancerbio-060424-052905
/content/journals/10.1146/annurev-cancerbio-060424-052905
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