Alcohol and smoking habits in association with hepatocellular carcinoma risk

Author Identifier

Nicola Bondonno: https://orcid.org/0000-0001-5905-444X

Document Type

Journal Article

Publication Title

International Journal of Cancer

PubMed ID

40098437

Publisher

Wiley

School

Nutrition and Health Innovation Research Institute / School of Medical and Health Sciences

Publication Unique Identifier

10.1002/ijc.35401

Funders

International Agency for Research on Cancer / Department of Epidemiology and Biostatistics / School of Public Health, Imperial College London / NIHR Imperial Biomedical Research Centre / Danish Cancer Society (Denmark) / Ligue Nationale Contre le Cancer / Institut Gustave Roussy / Mutuelle Générale de l'Éducation Nationale / Institut National de la Santé et de la Recherche Médicale / French National Research Agency (ANR-10-COHO-0006) / French Ministry for Higher Education (2102918823, 2103236497, 2103586016) / German Cancer Aid / German Cancer Research Center / German Institute of Human Nutrition Potsdam-Rehbrücke / Federal Ministry of Education and Research / Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy / Italian Ministry of Health / Italian Ministry of University and Research / Compagnia di San Paolo / Dutch Ministry of Public Health / Welfare and Sports / Netherlands Organisation for Health Research and Development / World Cancer Research Fund (WCRF) (The Netherlands); UiT The Arctic University of Norway; Health Research Fund (FIS)—Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia, and Navarra, and the Catalan Institute of Oncology—ICO / Swedish Cancer Society / Swedish Research Council / County Councils of Skåne and Västerbotten / Cancer Research UK (C864/A14136 to EPIC-Norfolk, C8221/A29017 to EPIC-Oxford) / Medical Research Council (MR/N003284/1, MC-UU_12015/1, MC_UU_00006/1 to EPIC-Norfolk; MR/Y013662/1 to EPIC-Oxford) (United Kingdom) / “Europe against Cancer” Programme of the European Commission / Cancer Prevention and Research Institute of Texas (RR200056)

Comments

Aglago, E. K., Ramos, I., Keski‐Rahkonen, P., Chatziioannou, C., Freisling, H., Fedirko, V., ... & Jenab, M. (2025). Alcohol and smoking habits in association with hepatocellular carcinoma risk. International Journal of Cancer. Advance online publication. https://doi.org/10.1002/ijc.35401

Abstract

We assessed hepatocellular carcinoma (HCC) risk associated with smoking and alcohol consumption and their interactions, using both questionnaire data and objective serum biomarkers. Information on smoking and alcohol consumption was collected at baseline from 450,112 participants of the EPIC cohort, among whom 255 developed HCC after a median follow-up of 14 years. In a nested case–control subset of 108 HCC cases and 108 matched controls, known biomarkers of smoking (cotinine, nicotine) and habitual alcohol consumption (2-hydroxy-3-methylbutyric acid) were annotated from untargeted metabolomics features. Multivariable-adjusted hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were computed, and multiplicative and additive interaction parameters were calculated. Compared to never smokers, current smokers had a higher HCC risk (HR = 2.46, 95% CI = 1.77–3.43) dose-dependently with the number of cigarettes smoked per day (Ptrend <.001). Compared to light drinkers, HCC risk was higher in former (HR = 3.20, 95% CI = 1.70–6.03), periodically heavy (HR = 1.98, 95% CI = 1.11–3.54), and always heavy (HR = 5.51, 95% CI = 2.39–12.7) drinkers. Higher HCC risk was also observed in the highest versus the lowest tertiles of cotinine (OR = 4.88, 95% CI = 1.52–15.70), nicotine (OR = 5.80, 95% CI = 1.33–25.30) and 2-hydroxy-3-methylbutyric acid (OR = 5.89, 95% CI = 1.33–26.12). Questionnaire-assessed smoking and alcohol exposures did not demonstrate an HCC risk interaction at the multiplicative (MI = 0.88, 95% CI = 0.40–1.96) or additive (RERI = 0.71, 95% CI = −10.1 to 23.6; attributable proportion = 0.17, 95% CI = −0.52 to 1.16; synergy index = 1.27, 95% CI = 0.98–1.66) scales. Similar analyses with cotinine, nicotine, and 2-hydroxy-3-methylbutyric acid also did not show interactions between smoking and alcohol consumption on HCC risk. Smoking and alcohol consumption are strong independent risk factors for HCC and do not appear to synergistically impact its risk, but larger studies are needed.

DOI

10.1002/ijc.35401

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