title: Prediagnostic selenium status and hepatobiliary cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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-μg/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).
  
  
  
  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.
authors.affiliation: Department of Physiology and Centre for Systems Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland; davidhughes@rcsi.ie.
authors.forename: David J
authors.initials: DJ
authors.lastname: Hughes
authors.affiliation: Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France; Institut Universitari d'Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol), Barcelona, Spain;
authors.forename: Talita
authors.initials: T
authors.lastname: Duarte-Salles
authors.affiliation: Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Berlin, Berlin, Germany;
authors.forename: Sandra
authors.initials: S
authors.lastname: Hybsier
authors.affiliation: Hellenic Health Foundation, Athens, Greece; WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology, and Medical Statistics, University of Athens Medical School, Athens, Greece;
authors.forename: Antonia
authors.initials: A
authors.lastname: Trichopoulou
authors.affiliation: Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France;
authors.forename: Magdalena
authors.initials: M
authors.lastname: Stepien
authors.affiliation: Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Nuthetal, Germany;
authors.forename: Krasimira
authors.initials: K
authors.lastname: Aleksandrova
authors.affiliation: Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark;
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.affiliation: Danish Cancer Society Research Center, Copenhagen, Denmark;
authors.forename: Anne
authors.initials: A
authors.lastname: Tjønneland
authors.affiliation: Danish Cancer Society Research Center, Copenhagen, Denmark;
authors.forename: Anja
authors.initials: A
authors.lastname: Olsen
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), CESP Center for Research in Epidemiology and Population Health, U1018, Villejuif, France; Université Paris Sud, UMRS 1018, Villejuif, France; Institute Gustave Roussy, Villejuif, France;
authors.forename: Aurélie
authors.initials: A
authors.lastname: Affret
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), CESP Center for Research in Epidemiology and Population Health, U1018, Villejuif, France; Université Paris Sud, UMRS 1018, Villejuif, France; Institute Gustave Roussy, Villejuif, France;
authors.forename: Guy
authors.initials: G
authors.lastname: Fagherazzi
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), CESP Center for Research in Epidemiology and Population Health, U1018, Villejuif, France; Université Paris Sud, UMRS 1018, Villejuif, France; Institute Gustave Roussy, Villejuif, France;
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Boutron-Ruault
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany;
authors.forename: Verena
authors.initials: V
authors.lastname: Katzke
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany;
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
authors.affiliation: Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Nuthetal, Germany;
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.affiliation: Hellenic Health Foundation, Athens, Greece; WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology, and Medical Statistics, University of Athens Medical School, Athens, Greece;
authors.forename: Christina
authors.initials: C
authors.lastname: Bamia
authors.affiliation: Hellenic Health Foundation, Athens, Greece; WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology, and Medical Statistics, University of Athens Medical School, Athens, Greece; Department of Epidemiology, Harvard School of Public Health, Boston, MA;
authors.forename: Pagona
authors.initials: P
authors.lastname: Lagiou
authors.affiliation: Hellenic Health Foundation, Athens, Greece;
authors.forename: Eleni
authors.initials: E
authors.lastname: Peppa
authors.affiliation: Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute-ISPO, Florence, Italy;
authors.forename: Domenico
authors.initials: D
authors.lastname: Palli
authors.affiliation: Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy;
authors.forename: Vittorio
authors.initials: V
authors.lastname: Krogh
authors.affiliation: Dipartimento di Medicina Clinica e Chirurgia Federico II, Naples, Italy;
authors.forename: Salvatore
authors.initials: S
authors.lastname: Panico
authors.affiliation: Cancer Registry and Histopathology Unit, "Civic-M.P. Arezzo" Hospital, ASP Ragusa, Italy;
authors.forename: Rosario
authors.initials: R
authors.lastname: Tumino
authors.affiliation: Unit of Cancer Epidemiology, Citta' della Salute e della Scienza Hospital-University of Turin and Center for Cancer Prevention, Turin, Italy;
authors.forename: Carlotta
authors.initials: C
authors.lastname: Sacerdote
authors.affiliation: Department for Determinants of Chronic Diseases, National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom;
authors.forename: Hendrik Bastiaan
authors.initials: HB
authors.lastname: Bueno-de-Mesquita
authors.affiliation: Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands; MRC-PHE Centre for Environment and Health.
authors.forename: Petra H
authors.initials: PH
authors.lastname: Peeters
authors.affiliation: The Norwegian Scientific Committee for Food Safety (VKM), Oslo, Norway;
authors.forename: Dagrun
authors.initials: D
authors.lastname: Engeset
authors.affiliation: Department of Community Medicine, Faculty of Health Sciences, University of Tromsø-The Arctic University of Norway, Tromsø, Norway; Department of Research, Cancer Registry of Norway, Oslo, Norway; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland;
authors.forename: Elisabete
authors.initials: E
authors.lastname: Weiderpass
authors.affiliation: Oviedo University, Oviedo, Spain;
authors.forename: Cristina
authors.initials: C
authors.lastname: Lasheras
authors.affiliation: Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain;
authors.forename: Antonio
authors.initials: A
authors.lastname: Agudo
authors.affiliation: Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs Granada, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain; Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain;
authors.forename: Maria-José
authors.initials: MJ
authors.lastname: Sánchez
authors.affiliation: CIBER de Epidemiología y Salud Pública (CIBERESP), Spain; Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain; Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain;
authors.forename: Carmen
authors.initials: C
authors.lastname: Navarro
authors.affiliation: CIBER de Epidemiología y Salud Pública (CIBERESP), Spain; Navarra Public Health Institute, Pamplona, Spain; IdiSNA, Navarra Institute for Health Research, Pamplona, Spain;
authors.forename: Eva
authors.initials: E
authors.lastname: Ardanaz
authors.affiliation: Public Health Direction and Biodonostia-Ciberesp, Basque Regional Health Department, San Sebastian, Spain;
authors.forename: Miren
authors.initials: M
authors.lastname: Dorronsoro
authors.affiliation: Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden;
authors.forename: Oskar
authors.initials: O
authors.lastname: Hemmingsson
authors.affiliation: MRC Epidemiology Unit and.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Wareham
authors.affiliation: Clinical Gerontology, School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom; and.
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.affiliation: Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Bradbury
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom;
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Cross
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom;
authors.forename: Marc
authors.initials: M
authors.lastname: Gunter
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom;
authors.forename: Elio
authors.initials: E
authors.lastname: Riboli
authors.affiliation: Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France;
authors.forename: Isabelle
authors.initials: I
authors.lastname: Romieu
authors.affiliation: Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Berlin, Berlin, Germany;
authors.forename: Lutz
authors.initials: L
authors.lastname: Schomburg
authors.affiliation: Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France;
authors.forename: Mazda
authors.initials: M
authors.lastname: Jenab
mesh_terms: D000368:Aged; D001652:Bile Ducts / Q000473:pathology; D001661:Biliary Tract Neoplasms / Q000097:blood / Q000209:etiology*; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000209:etiology*; D016022:Case-Control Studies; D003677:Deficiency Diseases / Q000097:blood / Q000150:complications* / Q000453:epidemiology; D005060:Europe / Q000453:epidemiology; D005260:Female; D005704:Gallbladder / Q000473:pathology; D006801:Humans; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000097:blood / Q000209:etiology*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009752:Nutritional Status; D016017:Odds Ratio; D011446:Prospective Studies; D012307:Risk Factors; D012643:Selenium / Q000097:blood / Q000172:deficiency*; D051149:Selenoprotein P / Q000097:blood*
chemical_list: D051149:Selenoprotein P; D012643:Selenium
keywords: hepatobiliary cancer; hepatocellular carcinoma; liver cancer; prospective cohort; selenium; selenium status; selenoprotein P