TY - JOUR
T1 - Alcohol and smoking habits in association with hepatocellular carcinoma risk
AU - Aglago, Elom K.
AU - Ramos, Ines
AU - Keski-Rahkonen, Pekka
AU - Chatziioannou, Chrysovalantou
AU - Freisling, Heinz
AU - Fedirko, Veronika
AU - Gunter, Marc J.
AU - Dahm, Christina C.
AU - Langmann, Fie
AU - Bondonno, Nicola
AU - Tjønneland, Anne
AU - Severi, Gianluca
AU - Truong, Therese
AU - Katzke, Verena
AU - Kaaks, Rudolf
AU - Bergmann, Manuela
AU - Schulze, Matthias B.
AU - Masala, Giovanna
AU - Pala, Valeria
AU - de Magistris, Maria Santucci
AU - Di Girolamo, Chiara
AU - Lukic, Marko
AU - Gram, Inger Torhild
AU - Bonet, Catalina
AU - Sánchez, Maria Jose
AU - Chirlaque, María Dolores
AU - Amiano, Pilar
AU - Guevara, Marcela
AU - Vermeulen, Roel
AU - Manjer, Jonas
AU - Eriksson, Linda
AU - Key, Tim J.
AU - Mayen, Ana Lucia
AU - Dossus, Laure
AU - Weiderpass, Elisabete
AU - Heath, Alicia K.
AU - Ferrari, Pietro
AU - Jenab, Mazda
N1 - Publisher Copyright:
© 2025 UICC.
PY - 2025/1/1
Y1 - 2025/1/1
N2 - 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.
AB - 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.
KW - biological markers
KW - ethanol
KW - interaction
KW - liver cancer
KW - tobacco
UR - http://www.scopus.com/inward/record.url?scp=105000825625&partnerID=8YFLogxK
U2 - 10.1002/ijc.35401
DO - 10.1002/ijc.35401
M3 - Article
C2 - 40098437
AN - SCOPUS:105000825625
SN - 0020-7136
JO - International Journal of Cancer
JF - International Journal of Cancer
ER -