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 MC., 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 MJ., Navarro C., Ardanaz E., Dorronsoro M., Hemmingsson O., Wareham NJ., Khaw KT., 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.