Prediagnostic selenium status and hepatobiliary cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort.
Hughes DJ., Duarte-Salles T., Hybsier S., Trichopoulou A., Stepien M., Aleksandrova K., Overvad K., Tjønneland A., Olsen A., Affret A., Fagherazzi G., Boutron-Ruault M-C., Katzke V., Kaaks R., Boeing H., Bamia C., Lagiou P., Peppa E., Palli D., Krogh V., Panico S., Tumino R., Sacerdote C., Bueno-de-Mesquita HB., Peeters PH., Engeset D., Weiderpass E., Lasheras C., Agudo A., Sánchez M-J., Navarro C., Ardanaz E., Dorronsoro M., Hemmingsson O., Wareham NJ., Khaw K-T., Bradbury KE., Cross AJ., Gunter M., Riboli E., Romieu I., Schomburg L., Jenab M.
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.