Dairy products and risk of hepatocellular carcinoma: The European Prospective Investigation into Cancer and Nutrition

International Journal of Cancer, Wiley, ISSN 0020-7136

Volume 135, 7, 2014

DOI:10.1002/ijc.28812, Dimensions: pub.1037523728, PMID: 24615266,



  1. (1) International Agency For Research On Cancer, grid.17703.32
  2. (2) Department of Epidemiology; Rollins School of Public Health; Emory University; Atlanta GA
  3. (3) Winship Cancer Institute; Emory University; Atlanta GA
  4. (4) Hellenic Health Foundation, grid.424637.0
  5. (5) National and Kapodistrian University of Athens, grid.5216.0
  6. (6) Academy of Athens, grid.417593.d
  7. (7) Department of Epidemiology; Harvard School of Public Health; Boston MA
  8. (8) German Cancer Research Center, grid.7497.d
  9. (9) Umeå University, grid.12650.30
  10. (10) Centre de Bioloqie Republique; Lyon France
  11. (11) Aarhus University, grid.7048.b, AU
  12. (12) Diet, Genes and Environment; Danish Cancer Society Research Center; Copenhagen Denmark
  13. (13) IGR, F-94805; Villejuif France
  14. (14) INSERM; Centre for Research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health team; F-94805, Villejuif France
  15. (15) University of Paris-Sud, grid.5842.b
  16. (16) German Institute of Human Nutrition, grid.418213.d
  17. (17) Icahn School of Medicine at Mount Sinai, grid.59734.3c
  18. (18) Istituto per lo Studio e la Prevenzione Oncologica, grid.417623.5
  19. (19) Fondazione IRCCS Istituto Nazionale dei Tumori, grid.417893.0
  20. (20) Cancer Registry and Histopathology Unit; “Civic-M.P.Arezzo” Hospital; ASP Ragusa Italy
  21. (21) Human Genetics Foundation, grid.428948.b
  22. (22) University of Turin, grid.7605.4
  23. (23) University of Naples Federico II, grid.4691.a
  24. (24) National Institute for Public Health and the Environment, grid.31147.30
  25. (25) University Medical Center Utrecht, grid.7692.a
  26. (26) Department of Epidemiology and Biostatistics; School of Public Health, Faculty of Medicine, Imperial College London; London United Kingdom
  27. (27) Julius Center, University Medical Center Utrecht; Utrecht The Netherlands
  28. (28) Cancer Registry of Norway, grid.418941.1
  29. (29) Department of Research; Cancer Registry of Norway; Oslo Norway
  30. (30) Folkhälsans Forskningscentrum, grid.428673.c
  31. (31) Karolinska Institute, grid.4714.6
  32. (32) Department of Community Medicine, Faculty of Health Sciences; UiT The Arctic University of Norway; Tromsø Norway
  33. (33) The Arctic University of Norway, grid.10919.30
  34. (34) Department of Nutrition; University of Oslo; Oslo Norway
  35. (35) Public Health Directorate; Asturias Spain
  36. (36) Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology, ICO‐IDIBELL, L'Hospitalet de Llobregat Spain
  37. (37) Andalusian School of Public Health, grid.413740.5
  38. (38) Instituto de Investigación Biosanitaria, grid.507088.2
  39. (39) Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiología y Salud Pública-CIBERESP); Madrid Spain
  40. (40) Public Health Division of Gipuzkoa, Basque Regional Health Department and CIBERESP-BIODONOSTIA; San Sebastian Spain
  41. (41) Department of Epidemiology; Murcia Regional Health Council; Murcia Spain
  42. (42) University of Murcia, grid.10586.3a
  43. (43) Instituto de Salud Pública de Navarra, grid.419126.9
  44. (44) University of Gothenburg, grid.8761.8
  45. (45) Lund University, grid.4514.4
  46. (46) University of Cambridge, grid.5335.0
  47. (47) MRC Epidemiology Unit, grid.415056.3
  48. (48) University of Oxford, grid.4991.5


Intake of dairy products has been associated with risk of some cancers, but findings are often inconsistent and information on hepatocellular carcinoma (HCC) risk is limited, particularly from prospective settings. The aim of our study was to investigate the association between consumption of total and specific dairy products (milk/cheese/yogurt) and their components (calcium/vitamin D/fats/protein), with first incident HCC (N(cases) = 191) in the European Prospective Investigation into Cancer and Nutrition cohort, including a nested case-control subset (N(cases) = 122) with the assessment of hepatitis B virus/hepatitis C virus infections status, liver damage and circulating insulin-like growth factor (IGF)-I levels. For cohort analyses, multivariable-adjusted Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI). For nested case-control analyses, conditional logistic regression was used to calculate odds ratios and 95% CI. A total of 477,206 participants were followed-up for an average of 11 years (person-years follow-up = 5,415,385). In the cohort study, a significant positive HCC risk association was observed for total dairy products (highest vs. lowest tertile, HR = 1.66, 95% CI: 1.13-2.43; p(trend) = 0.012), milk (HR = 1.51, 95% CI: 1.02-2.24; p(trend) = 0.049), and cheese (HR = 1.56, 95% CI: 1.02-2.38; p(trend) = 0.101), but not yogurt (HR = 0.94, 95% CI: 0.65-1.35). Dietary calcium, vitamin D, fat and protein from dairy sources were associated with increased HCC risk, whereas the same nutrients from nondairy sources showed inverse or null associations. In the nested case-control study, similar results were observed among hepatitis-free individuals. Results from this large prospective cohort study suggest that higher consumption of dairy products, particularly milk and cheese, may be associated with increased HCC risk. Validation of these findings in other populations is necessary. Potential biologic mechanisms require further exploration.


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