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

Talita Duarte-Salles, Veronika Fedirko, Magdalena Stepien, Antonia Trichopoulou, Christina Bamia, Pagona Lagiou, Annekatrin Lukanova, Elisabeth Trepo, Kim Overvad, Anne Tjønneland, Jytte Halkjær, Marie Christine Boutron-Ruault, Antoine Racine, Claire Cadeau, Tilman Kühn, Krasimira Aleksandrova, Dimitrios Trichopoulos, Konstantinos Tsiotas, Paolo Boffetta, Domenico PalliValeria Pala, Rosario Tumino, Carlotta Sacerdote, Salvatore Panico, H. B. Bueno-De-Mesquita, Vincent K. Dik, Petra H. Peeters, Elisabete Weiderpass, Inger Torhild Gram, Anette Hjartåker, Jose Ramõn Quirõs, Ana Fonseca-Nunes, Esther Molina-Montes, Miren Dorronsoro, Carmen Navarro Sanchez, Aurelio Barricarte, Björn Lindkvist, Emily Sonestedt, Ingegerd Johansson, Maria Wennberg, Kay Tee Khaw, Nick Wareham, Ruth C. Travis, Isabelle Romieu, Elio Riboli, Mazda Jenab

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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 (Ncases = 191) in the European Prospective Investigation into Cancer and Nutrition cohort, including a nested case-control subset (Ncases = 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; ptrend = 0.012), milk (HR = 1.51, 95% CI: 1.02-2.24; ptrend = 0.049), and cheese (HR = 1.56, 95% CI: 1.02-2.38; ptrend = 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. What's New? Currently, the role of dairy product intake in the development of hepatocellular carcinoma (HCC) is unclear. Using detailed data from a large multi-centric prospective cohort, this study investigated the association between consumption of total and specific dairy products with first incident HCC. The study found that higher dairy product consumption, particularly milk and cheese, was associated with increased HCC risk. Dietary calcium, vitamin D, fat and protein did not explain the observed associations. However, higher circulating IGF-I levels may play a role.

Original languageEnglish
Pages (from-to)1662-1672
Number of pages11
JournalInternational Journal of Cancer
Volume135
Issue number7
DOIs
Publication statusPublished - Oct 1 2014

Fingerprint

Dairy Products
Hepatocellular Carcinoma
Cheese
Confidence Intervals
Neoplasms
Milk
Cohort Studies
Vitamin D
Dietary Calcium
Yogurt
Fats
Insulin-Like Growth Factor I
Prospective Studies
Proteins
Virus Diseases
Proportional Hazards Models
Hepatitis B virus
Hepacivirus
Hepatitis
Case-Control Studies

Keywords

  • calcium
  • dairy products
  • hepatocellular carcinoma
  • prospective cohort

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Duarte-Salles, T., Fedirko, V., Stepien, M., Trichopoulou, A., Bamia, C., Lagiou, P., ... Jenab, M. (2014). Dairy products and risk of hepatocellular carcinoma: The European Prospective Investigation into Cancer and Nutrition. International Journal of Cancer, 135(7), 1662-1672. https://doi.org/10.1002/ijc.28812

Dairy products and risk of hepatocellular carcinoma : The European Prospective Investigation into Cancer and Nutrition. / Duarte-Salles, Talita; Fedirko, Veronika; Stepien, Magdalena; Trichopoulou, Antonia; Bamia, Christina; Lagiou, Pagona; Lukanova, Annekatrin; Trepo, Elisabeth; Overvad, Kim; Tjønneland, Anne; Halkjær, Jytte; Boutron-Ruault, Marie Christine; Racine, Antoine; Cadeau, Claire; Kühn, Tilman; Aleksandrova, Krasimira; Trichopoulos, Dimitrios; Tsiotas, Konstantinos; Boffetta, Paolo; Palli, Domenico; Pala, Valeria; Tumino, Rosario; Sacerdote, Carlotta; Panico, Salvatore; Bueno-De-Mesquita, H. B.; Dik, Vincent K.; Peeters, Petra H.; Weiderpass, Elisabete; Torhild Gram, Inger; Hjartåker, Anette; Ramõn Quirõs, Jose; Fonseca-Nunes, Ana; Molina-Montes, Esther; Dorronsoro, Miren; Navarro Sanchez, Carmen; Barricarte, Aurelio; Lindkvist, Björn; Sonestedt, Emily; Johansson, Ingegerd; Wennberg, Maria; Khaw, Kay Tee; Wareham, Nick; Travis, Ruth C.; Romieu, Isabelle; Riboli, Elio; Jenab, Mazda.

In: International Journal of Cancer, Vol. 135, No. 7, 01.10.2014, p. 1662-1672.

Research output: Contribution to journalArticle

Duarte-Salles, T, Fedirko, V, Stepien, M, Trichopoulou, A, Bamia, C, Lagiou, P, Lukanova, A, Trepo, E, Overvad, K, Tjønneland, A, Halkjær, J, Boutron-Ruault, MC, Racine, A, Cadeau, C, Kühn, T, Aleksandrova, K, Trichopoulos, D, Tsiotas, K, Boffetta, P, Palli, D, Pala, V, Tumino, R, Sacerdote, C, Panico, S, Bueno-De-Mesquita, HB, Dik, VK, Peeters, PH, Weiderpass, E, Torhild Gram, I, Hjartåker, A, Ramõn Quirõs, J, Fonseca-Nunes, A, Molina-Montes, E, Dorronsoro, M, Navarro Sanchez, C, Barricarte, A, Lindkvist, B, Sonestedt, E, Johansson, I, Wennberg, M, Khaw, KT, Wareham, N, Travis, RC, Romieu, I, Riboli, E & Jenab, M 2014, 'Dairy products and risk of hepatocellular carcinoma: The European Prospective Investigation into Cancer and Nutrition', International Journal of Cancer, vol. 135, no. 7, pp. 1662-1672. https://doi.org/10.1002/ijc.28812
Duarte-Salles, Talita ; Fedirko, Veronika ; Stepien, Magdalena ; Trichopoulou, Antonia ; Bamia, Christina ; Lagiou, Pagona ; Lukanova, Annekatrin ; Trepo, Elisabeth ; Overvad, Kim ; Tjønneland, Anne ; Halkjær, Jytte ; Boutron-Ruault, Marie Christine ; Racine, Antoine ; Cadeau, Claire ; Kühn, Tilman ; Aleksandrova, Krasimira ; Trichopoulos, Dimitrios ; Tsiotas, Konstantinos ; Boffetta, Paolo ; Palli, Domenico ; Pala, Valeria ; Tumino, Rosario ; Sacerdote, Carlotta ; Panico, Salvatore ; Bueno-De-Mesquita, H. B. ; Dik, Vincent K. ; Peeters, Petra H. ; Weiderpass, Elisabete ; Torhild Gram, Inger ; Hjartåker, Anette ; Ramõn Quirõs, Jose ; Fonseca-Nunes, Ana ; Molina-Montes, Esther ; Dorronsoro, Miren ; Navarro Sanchez, Carmen ; Barricarte, Aurelio ; Lindkvist, Björn ; Sonestedt, Emily ; Johansson, Ingegerd ; Wennberg, Maria ; Khaw, Kay Tee ; Wareham, Nick ; Travis, Ruth C. ; Romieu, Isabelle ; Riboli, Elio ; Jenab, Mazda. / Dairy products and risk of hepatocellular carcinoma : The European Prospective Investigation into Cancer and Nutrition. In: International Journal of Cancer. 2014 ; Vol. 135, No. 7. pp. 1662-1672.
@article{46e33de1834e4be98b16018d2c7afc2b,
title = "Dairy products and risk of hepatocellular carcinoma: The European Prospective Investigation into Cancer and Nutrition",
abstract = "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 (Ncases = 191) in the European Prospective Investigation into Cancer and Nutrition cohort, including a nested case-control subset (Ncases = 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; ptrend = 0.012), milk (HR = 1.51, 95{\%} CI: 1.02-2.24; ptrend = 0.049), and cheese (HR = 1.56, 95{\%} CI: 1.02-2.38; ptrend = 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. What's New? Currently, the role of dairy product intake in the development of hepatocellular carcinoma (HCC) is unclear. Using detailed data from a large multi-centric prospective cohort, this study investigated the association between consumption of total and specific dairy products with first incident HCC. The study found that higher dairy product consumption, particularly milk and cheese, was associated with increased HCC risk. Dietary calcium, vitamin D, fat and protein did not explain the observed associations. However, higher circulating IGF-I levels may play a role.",
keywords = "calcium, dairy products, hepatocellular carcinoma, prospective cohort",
author = "Talita Duarte-Salles and Veronika Fedirko and Magdalena Stepien and Antonia Trichopoulou and Christina Bamia and Pagona Lagiou and Annekatrin Lukanova and Elisabeth Trepo and Kim Overvad and Anne Tj{\o}nneland and Jytte Halkj{\ae}r and Boutron-Ruault, {Marie Christine} and Antoine Racine and Claire Cadeau and Tilman K{\"u}hn and Krasimira Aleksandrova and Dimitrios Trichopoulos and Konstantinos Tsiotas and Paolo Boffetta and Domenico Palli and Valeria Pala and Rosario Tumino and Carlotta Sacerdote and Salvatore Panico and Bueno-De-Mesquita, {H. B.} and Dik, {Vincent K.} and Peeters, {Petra H.} and Elisabete Weiderpass and {Torhild Gram}, Inger and Anette Hjart{\aa}ker and {Ram{\~o}n Quir{\~o}s}, Jose and Ana Fonseca-Nunes and Esther Molina-Montes and Miren Dorronsoro and {Navarro Sanchez}, Carmen and Aurelio Barricarte and Bj{\"o}rn Lindkvist and Emily Sonestedt and Ingegerd Johansson and Maria Wennberg and Khaw, {Kay Tee} and Nick Wareham and Travis, {Ruth C.} and Isabelle Romieu and Elio Riboli and Mazda Jenab",
year = "2014",
month = "10",
day = "1",
doi = "10.1002/ijc.28812",
language = "English",
volume = "135",
pages = "1662--1672",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "7",

}

TY - JOUR

T1 - Dairy products and risk of hepatocellular carcinoma

T2 - The European Prospective Investigation into Cancer and Nutrition

AU - Duarte-Salles, Talita

AU - Fedirko, Veronika

AU - Stepien, Magdalena

AU - Trichopoulou, Antonia

AU - Bamia, Christina

AU - Lagiou, Pagona

AU - Lukanova, Annekatrin

AU - Trepo, Elisabeth

AU - Overvad, Kim

AU - Tjønneland, Anne

AU - Halkjær, Jytte

AU - Boutron-Ruault, Marie Christine

AU - Racine, Antoine

AU - Cadeau, Claire

AU - Kühn, Tilman

AU - Aleksandrova, Krasimira

AU - Trichopoulos, Dimitrios

AU - Tsiotas, Konstantinos

AU - Boffetta, Paolo

AU - Palli, Domenico

AU - Pala, Valeria

AU - Tumino, Rosario

AU - Sacerdote, Carlotta

AU - Panico, Salvatore

AU - Bueno-De-Mesquita, H. B.

AU - Dik, Vincent K.

AU - Peeters, Petra H.

AU - Weiderpass, Elisabete

AU - Torhild Gram, Inger

AU - Hjartåker, Anette

AU - Ramõn Quirõs, Jose

AU - Fonseca-Nunes, Ana

AU - Molina-Montes, Esther

AU - Dorronsoro, Miren

AU - Navarro Sanchez, Carmen

AU - Barricarte, Aurelio

AU - Lindkvist, Björn

AU - Sonestedt, Emily

AU - Johansson, Ingegerd

AU - Wennberg, Maria

AU - Khaw, Kay Tee

AU - Wareham, Nick

AU - Travis, Ruth C.

AU - Romieu, Isabelle

AU - Riboli, Elio

AU - Jenab, Mazda

PY - 2014/10/1

Y1 - 2014/10/1

N2 - 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 (Ncases = 191) in the European Prospective Investigation into Cancer and Nutrition cohort, including a nested case-control subset (Ncases = 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; ptrend = 0.012), milk (HR = 1.51, 95% CI: 1.02-2.24; ptrend = 0.049), and cheese (HR = 1.56, 95% CI: 1.02-2.38; ptrend = 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. What's New? Currently, the role of dairy product intake in the development of hepatocellular carcinoma (HCC) is unclear. Using detailed data from a large multi-centric prospective cohort, this study investigated the association between consumption of total and specific dairy products with first incident HCC. The study found that higher dairy product consumption, particularly milk and cheese, was associated with increased HCC risk. Dietary calcium, vitamin D, fat and protein did not explain the observed associations. However, higher circulating IGF-I levels may play a role.

AB - 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 (Ncases = 191) in the European Prospective Investigation into Cancer and Nutrition cohort, including a nested case-control subset (Ncases = 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; ptrend = 0.012), milk (HR = 1.51, 95% CI: 1.02-2.24; ptrend = 0.049), and cheese (HR = 1.56, 95% CI: 1.02-2.38; ptrend = 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. What's New? Currently, the role of dairy product intake in the development of hepatocellular carcinoma (HCC) is unclear. Using detailed data from a large multi-centric prospective cohort, this study investigated the association between consumption of total and specific dairy products with first incident HCC. The study found that higher dairy product consumption, particularly milk and cheese, was associated with increased HCC risk. Dietary calcium, vitamin D, fat and protein did not explain the observed associations. However, higher circulating IGF-I levels may play a role.

KW - calcium

KW - dairy products

KW - hepatocellular carcinoma

KW - prospective cohort

UR - http://www.scopus.com/inward/record.url?scp=84904514263&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84904514263&partnerID=8YFLogxK

U2 - 10.1002/ijc.28812

DO - 10.1002/ijc.28812

M3 - Article

C2 - 24615266

AN - SCOPUS:84904514263

VL - 135

SP - 1662

EP - 1672

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 7

ER -