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@ARTICLE{Aglago:300131,
      author       = {E. K. Aglago and I. Ramos and P. Keski-Rahkonen and C.
                      Chatziioannou and H. Freisling and V. Fedirko and M. J.
                      Gunter and C. C. Dahm and F. Langmann and N. Bondonno and A.
                      Tjønneland and G. Severi and T. Truong and V. Katzke$^*$
                      and R. Kaaks$^*$ and M. Bergmann and M. B. Schulze and G.
                      Masala and V. Pala and M. S. de Magistris and C. Di Girolamo
                      and M. Lukic and I. T. Gram and C. Bonet and M.-J. Sánchez
                      and M.-D. Chirlaque and P. Amiano and M. Guevara and R.
                      Vermeulen and J. Manjer and L. Eriksson and T. J. Key and
                      A.-L. Mayen and L. Dossus and E. Weiderpass and A. K. Heath
                      and P. Ferrari and M. Jenab},
      title        = {{A}lcohol and smoking habits in association with
                      hepatocellular carcinoma risk.},
      journal      = {International journal of cancer},
      volume       = {157},
      number       = {4},
      issn         = {0020-7136},
      address      = {Bognor Regis},
      publisher    = {Wiley-Liss},
      reportid     = {DKFZ-2025-00628},
      pages        = {644-657},
      year         = {2025},
      note         = {2025 Aug 15;157(4):644-657},
      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.},
      keywords     = {biological markers (Other) / ethanol (Other) / interaction
                      (Other) / liver cancer (Other) / tobacco (Other)},
      cin          = {C020},
      ddc          = {610},
      cid          = {I:(DE-He78)C020-20160331},
      pnm          = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
      pid          = {G:(DE-HGF)POF4-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40098437},
      doi          = {10.1002/ijc.35401},
      url          = {https://inrepo02.dkfz.de/record/300131},
}