The complexity of tobacco smoke-induced mutagenesis in head and neck cancer

Tobacco smoke, alone or combined with alcohol, is the predominant cause of head and neck cancer (HNC). We explore how tobacco exposure contributes to cancer development by mutational signature analysis of 265 whole-genome sequenced HNC samples from eight countries. Six tobacco-associated mutational signatures were detected, including some not previously reported. Differences in HNC incidence between countries corresponded with differences in mutation burdens of tobacco-associated signatures, consistent with the dominant role of tobacco in HNC causation. Differences were found in the burden of tobacco-associated signatures between anatomical subsites, suggesting that tissue-specific factors modulate mutagenesis. We identified an association between tobacco smoking and alcohol-related signatures, indicating a combined effect of these exposures. Tobacco smoking was associated with differences in the mutational spectra, repertoire of driver mutations in cancer genes and patterns of copy number change. Our results demonstrate the multiple pathways by which tobacco smoke can influence the evolution of cancer cell clones.

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Publication Details

Journal
Nature Genetics
Published
2025-03-31
DOI
https://doi.org/10.1038/s41588-025-02134-0
Citations
12
Primary Topic
Cancer Genomics and Diagnostics
Type
article
Field-Weighted Citation Impact
11.23
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The complexity of tobacco smoke-induced mutagenesis in head and neck cancer

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The complexity of tobacco smoke-induced mutagenesis in head and neck cancer

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article en
12 citations

Abstract

Tobacco smoke, alone or combined with alcohol, is the predominant cause of head and neck cancer (HNC). We explore how tobacco exposure contributes to cancer development by mutational signature analysis of 265 whole-genome sequenced HNC samples from eight countries. Six tobacco-associated mutational signatures were detected, including some not previously reported. Differences in HNC incidence between countries corresponded with differences in mutation burdens of tobacco-associated signatures, consistent with the dominant role of tobacco in HNC causation. Differences were found in the burden of tobacco-associated signatures between anatomical subsites, suggesting that tissue-specific factors modulate mutagenesis. We identified an association between tobacco smoking and alcohol-related signatures, indicating a combined effect of these exposures. Tobacco smoking was associated with differences in the mutational spectra, repertoire of driver mutations in cancer genes and patterns of copy number change. Our results demonstrate the multiple pathways by which tobacco smoke can influence the evolution of cancer cell clones.

Nature GeneticsVol. 57(4)
University of Padua (IT), Carol Davila University of Medicine and Pharmacy (RO), Universidade de São Paulo (BR), National and Kapodistrian University of Athens (GR), Charles University (CZ), Universidad de Buenos Aires (AR), Clinical Emergency Hospital Bucharest (RO), Santa Casa Hospital (BR), Wellcome Sanger Institute (GB), AC Camargo Hospital (BR), University of California San Diego (US), University of Oxford (GB), Hospital de Câncer de Barretos (BR), Public Health Authority of the Slovak Republic (SK), Hospital Araújo Jorge (BR), Centro di Riferimento Oncologico (IT), Fundación Santa Fe de Bogotá (CO), La Jolla Bioengineering Institute (US), Instituto Nacional de Câncer - INCA (BR), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Centre international de recherche sur le cancer (FR), Universidade Federal do Espírito Santo (BR)
Good health and well-being
Openalex Percentile: Top 1%
Cancer Genomics and Diagnostics
11.23
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