Alcohol and smoking habits in association with hepatocellular carcinoma risk

• DOI: 10.1002/ijc.35401
• Publication Date: 2025-03-18T07:20:26Z
• Authors: Elom K. Aglago; Ines Ramos; Pekka Keski‐Rahkonen; Chrysovalantou Ch...; Heinz Freisling; Veronika Fedirko; Marc J. Gunter; Christina C. Dahm; Fie Langmann; Nicola Bondonno; Anne Tjønneland; Gianluca Severi; Therese Truong; Verena Katzke; Rudolf Kaaks; Manuela Bergmann; Matthias B. Schulze; Giovanna Masala; Valeria Pala; Maria Santucci de...; Chiara Di Girolamo; Marko Lukic; Inger Torhild Gram; Catalina Bonet; Maria‐Jose Sánchez; María‐Dolores Chi...; Pilar Amiano; Marcela Guevara; Roel Vermeulen; Jonas Manjer; Linda Eriksson; Tim J. Key; Ana‐Lucia Mayen; Laure Dossus; Elisabete Weiderpass; Alicia K. Heath; Pietro Ferrari; Mazda Jenab
• Keywords: Cotinine

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