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

Am J Clin Nutr. 2016 Aug;104(2):406-14. doi: 10.3945/ajcn.116.131672. Epub 2016 Jun 29.

Abstract

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.

Keywords: hepatobiliary cancer; hepatocellular carcinoma; liver cancer; prospective cohort; selenium; selenium status; selenoprotein P.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Bile Ducts / pathology
  • Biliary Tract Neoplasms / blood
  • Biliary Tract Neoplasms / etiology*
  • Carcinoma, Hepatocellular / blood
  • Carcinoma, Hepatocellular / etiology*
  • Case-Control Studies
  • Deficiency Diseases / blood
  • Deficiency Diseases / complications*
  • Deficiency Diseases / epidemiology
  • Europe / epidemiology
  • Female
  • Gallbladder / pathology
  • Humans
  • Liver / pathology
  • Liver Neoplasms / blood
  • Liver Neoplasms / etiology*
  • Logistic Models
  • Male
  • Middle Aged
  • Nutritional Status*
  • Odds Ratio
  • Prospective Studies
  • Risk Factors
  • Selenium / blood
  • Selenium / deficiency*
  • Selenoprotein P / blood*

Substances

  • Selenoprotein P
  • Selenium