Alcohol and tobacco in cancer: A unified framework of interaction across carcinogenic pathways and cancer types
Abstract
Background: Alcohol and tobacco are among the leading preventable causes of cancer worldwide and frequently co-occur. While both are well-established independent carcinogens, their combined effects remain insufficiently characterized and inconsistently interpreted across cancer types. Objective: This review synthesizes epidemiological and mechanistic evidence on alcohol-tobacco interaction in carcinogenesis, distinguishing statistical interaction from evidence of biological mechanism. Methods: We examined interaction patterns across major cancer sites and assess the extent to which combined effects exceed individual risks. Particular attention is given to methodological approaches used to quantify interaction, including additive and multiplicative models and their implications for causal interpretation. Results: Current evidence supports a heterogeneous landscape of interaction. Strong and consistent synergistic effects are observed for upper aerodigestive tract cancers, whereas evidence is heterogeneous for hepatocellular carcinoma and context-dependent for breast cancer. By contrast, lung, pancreatic, and early-onset colorectal cancers show predominantly independent effects, with tobacco remaining the principal driver of lung cancer. Mendelian randomization studies support independent causal effects of smoking and, for some cancers, alcohol, but have not assessed their joint interaction. Conclusion: To reconcile these findings, we propose a unified conceptual framework in which alcohol-tobacco interaction is viewed as a continuum ranging from strong biological synergy to functional independence, depending on tissue-specific vulnerability and exposure context. Finally, we identify key gaps in the field, including the need for standardized interaction metrics, prospective cohorts capturing joint exposure trajectories, integrative multi-omics approaches, and combined Mendelian randomization studies. Addressing these challenges will be essential to improve risk stratification and inform both precision oncology strategies and targeted, combined prevention efforts.
Related
- Grandparent Prenatal Tobacco, Alcohol, Coffee, and Tea Consumption and Autism in the Third Generation
- Reduced planning depth and stronger probability discounting in alcohol and tobacco use disorder
- The interaction between UDP-glycosyltransferase and CIPK11 regulates low nitrogen response in tobacco
- Crossed Pathways: Tobacco–Cannabis Co‐Use and Motivation to Quit in Young Adults in France
- Transcriptional control of higher alcohol formation in Saccharomyces cerevisiae: a systems framework linking nutrient sensing, precursor allocation, Ehrlich output, and stress adaptation
BibTeX
@article{bouajila2026alcohol,
title = {{Alcohol and tobacco in cancer: A unified framework of interaction across carcinogenic pathways and cancer types}},
author = {Naouras Bouajila and Bernard Srour and Camille Barrault and Anne Stoebner and Philippe Arvers and Gérard Peiffer and Jérôme Foucaud and Henri-Jean Aubin and Michael Bisch and Mickael Naassila},
journal = {Cancer Epidemiology},
year = {2026},
month = jul,
doi = {10.1016/j.canep.2026.103166},
url = {https://u-picardie.hal.science/hal-05712656v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Alcohol and tobacco in cancer: A unified framework of interaction across carcinogenic pathways and cancer types
AU - Naouras Bouajila
AU - Bernard Srour
AU - Camille Barrault
AU - Anne Stoebner
AU - Philippe Arvers
AU - Gérard Peiffer
AU - Jérôme Foucaud
AU - Henri-Jean Aubin
AU - Michael Bisch
AU - Mickael Naassila
PY - 2026
DA - 2026/07/31
JO - Cancer Epidemiology
DO - 10.1016/j.canep.2026.103166
UR - https://u-picardie.hal.science/hal-05712656v1
AB - Background: Alcohol and tobacco are among the leading preventable causes of cancer worldwide and frequently co-occur. While both are well-established independent carcinogens, their combined effects remain insufficiently characterized and inconsistently interpreted across cancer types. Objective: This review synthesizes epidemiological and mechanistic evidence on alcohol-tobacco interaction in carcinogenesis, distinguishing statistical interaction from evidence of biological mechanism. Methods: We examined interaction patterns across major cancer sites and assess the extent to which combined effects exceed individual risks. Particular attention is given to methodological approaches used to quantify interaction, including additive and multiplicative models and their implications for causal interpretation. Results: Current evidence supports a heterogeneous landscape of interaction. Strong and consistent synergistic effects are observed for upper aerodigestive tract cancers, whereas evidence is heterogeneous for hepatocellular carcinoma and context-dependent for breast cancer. By contrast, lung, pancreatic, and early-onset colorectal cancers show predominantly independent effects, with tobacco remaining the principal driver of lung cancer. Mendelian randomization studies support independent causal effects of smoking and, for some cancers, alcohol, but have not assessed their joint interaction. Conclusion: To reconcile these findings, we propose a unified conceptual framework in which alcohol-tobacco interaction is viewed as a continuum ranging from strong biological synergy to functional independence, depending on tissue-specific vulnerability and exposure context. Finally, we identify key gaps in the field, including the need for standardized interaction metrics, prospective cohorts capturing joint exposure trajectories, integrative multi-omics approaches, and combined Mendelian randomization studies. Addressing these challenges will be essential to improve risk stratification and inform both precision oncology strategies and targeted, combined prevention efforts.
SN - 1877-7821
ER -