Prediagnostic selenium status and hepatobiliary cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort

David J. Hughes*, Talita Duarte-Salles, Sandra Hybsier, Antonia Trichopoulou, Magdalena Stepien, Krasimira Aleksandrova, Kim Overvad, Anne Tjønneland, Anja Olsen, Aurélie Affret, Guy Fagherazzi, Marie Christine Boutron-Ruault, Verena Katzke, Rudolf Kaaks, Heiner Boeing, Christina Bamia, Pagona Lagiou, Eleni Peppa, Domenico Palli, Vittorio KroghSalvatore Panico, Rosario Tumino, Carlotta Sacerdote, Hendrik Bastiaan Bueno-De-Mesquita, Petra H. Peeters, Dagrun Engeset, Elisabete Weiderpass, Cristina Lasheras, Antonio Agudo, Maria José Sánchez, Carmen Navarro, Eva Ardanaz, Miren Dorronsoro, Oskar Hemmingsson, Nicholas J. Wareham, Kay Tee Khaw, Kathryn E. Bradbury, Amanda J. Cross, Marc Gunter, Elio Riboli, Isabelle Romieu, Lutz Schomburg, Mazda Jenab

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

66 Citations (Scopus)


Selenium status is suboptimal in many Europeans and may be a risk factor for the development of various cancers, including those of the liver and biliary tract. Objective: We wished to examine whether selenium status in advance of cancer onset is associated with hepatobiliary cancers in the EPIC (European Prospective Investigation into Cancer and Nutrition) study. Design: We assessed prediagnostic selenium status by measuring serum concentrations of selenium and selenoprotein P (SePP; the major circulating selenium transfer protein) and examined the association with hepatocellular carcinoma (HCC; n = 121), gallbladder and biliary tract cancers (GBTCs; n = 100), and intrahepatic bile duct cancer (IHBC; n = 40) risk in a nested case-control design within the EPIC study. Selenium was measured by total reflection X-ray fluorescence, and SePP was determined by a colorimetric sandwich ELISA. Multivariable ORs and 95% CIs were calculated by using conditional logistic regression. Results: HCC and GBTC cases, but not IHBC cases, showed significantly lower circulating selenium and SePP concentrations than their matched controls. Higher circulating selenium was associated with a significantly lower HCC risk (OR per 20-mg/L increase: 0.41; 95% CI: 0.23, 0.72) but not with the risk of GBTC or IHBC. Similarly, higher SePP concentrations were associated with lowered HCC risk only in both the categorical and continuous analyses (HCC: P-trend ≤ 0.0001; OR per 1.5-mg/L increase: 0.37; 95% CI: 0.21, 0.63). Conclusion: These findings from a large prospective cohort provide evidence that suboptimal selenium status in Europeans may be associated with an appreciably increased risk of HCC development.

Original languageEnglish
Pages (from-to)406-414
Number of pages9
JournalAmerican Journal of Clinical Nutrition
Issue number2
Publication statusPublished - 1 Aug 2016
Externally publishedYes


  • Hepatobiliary cancer
  • Hepatocellular carcinoma
  • Liver cancer
  • Prospective cohort
  • Selenium
  • Selenium status
  • Selenoprotein P


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