Prediagnostic selenium status and hepatobiliary cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort.
Hughes, David J
Bueno-de-Mesquita, Hendrik Bastiaan
Peeters, Petra H
Bradbury, Kathryn E
Cross, Amanda J
American Journal of Clinical Nutrition
American Society for Clinical Nutrition, Inc.
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Hughes, D. J., Duarte-Salles, T., Hybsier, S., Trichopoulou, A., Stepien, M., Aleksandrova, K., Overvad, K., et al. (2016). Prediagnostic selenium status and hepatobiliary cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort.. American Journal of Clinical Nutrition, 104 (2), 406-414. https://doi.org/10.3945/ajcn.116.131672
BACKGROUND: 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-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). 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.
hepatobiliary cancer, hepatocellular carcinoma, liver cancer, prospective cohort, selenium, selenium status, selenoprotein P, Aged, Bile Ducts, Biliary Tract Neoplasms, Carcinoma, Hepatocellular, Case-Control Studies, Deficiency Diseases, Europe, Female, Gallbladder, Humans, Liver, Liver Neoplasms, Logistic Models, Male, Middle Aged, Nutritional Status, Odds Ratio, Prospective Studies, Risk Factors, Selenium, Selenoprotein P
Funding for this study was provided jointly by the French National Cancer Institute [L’Institut National du Cancer; grant 2009-139; principal investigator (PI): MJ] and the Health Research Board of Ireland (award HRA_PHS/2013/397; PI: DJH) as well as the Deutsche Forschungsgemeinschaft (grant SCHO 849/4-1; PI: LS). The coordination of the European Prospective Investigation into Cancer and Nutrition (EPIC) is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by the Danish Cancer Society (Denmark); the Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, and Institut National de la Santé et de la Recherche Médicale (INSERM) (France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, and the Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and the National Research Council (Italy); the Dutch Ministry of Public Health, Welfare, and Sports (VWS), the Netherlands Cancer Registry, LK research funds, Dutch Prevention funds, Dutch ZON (Zorg Onderzoek Nederland), the World Cancer Research Fund, and Statistics Netherlands (Netherlands); the Nordic Centre of Excellence Programme on Food, Nutrition, and Health (Norway); the Health Research Fund (FIS; PI13/00061 to Granada) and regional governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236), and Navarra (ISCIII RETIC; RD06/0020) (Spain); the Swedish Cancer Society, the Swedish Scientific Council, and County Councils of Skåne and Västerbotten (Sweden); and Cancer Research UK [14136 to EPIC-Norfolk; C570/A16491 to EPIC-Oxford] and the Medical Research Council (1000143 to EPIC-Norfolk) (United Kingdom). LS was supported by Deutsche Forschungsgemeinschaft (GraKo 1208, SCHO849/4-1) and the Federal Ministry of Economics and Technology (BMWi; KF2263202CS2)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0512-10135)
MEDICAL RESEARCH COUNCIL (MR/N003284/1)
Medical Research Council (MC_U106179471)
Embargo Lift Date
External DOI: https://doi.org/10.3945/ajcn.116.131672
This record's URL: https://www.repository.cam.ac.uk/handle/1810/260264