title: Effects of selenium status and polymorphisms in selenoprotein genes on prostate cancer risk in a prospective study of European men.
abstract: BACKGROUND
  Evidence for an association between selenium status and prostate cancer risk is still inconclusive. Anticarcinogenic effects of selenium are supposedly mediated through cellular protective and redox properties of selenoenzymes in vivo. We evaluated the association between serum selenium status and prostate cancer risk in a population with relative low selenium concentrations considering effect modification by genetic variants in selenoprotein genes.
  
  
  METHODS
  A case-control study of 248 incident prostate cancer cases and 492 matched controls was nested within the EPIC-Heidelberg cohort. Baseline blood samples were analyzed for serum selenium and selenoprotein P concentrations and glutathione peroxidase activity. Genotyping was carried out for SEP15 (rs5859, rs540049), SEPP1 (rs3877899, rs7579), GPX1 (rs1050450), and GPX4 (rs713041). Conditional logistic regression was used to calculate adjusted odds ratios (OR) and 95% confidence intervals (95% CI).
  
  
  RESULTS
  The OR for prostate cancer was 0.89 (95% CI, 0.79-1.01) per 10 μg/L increase of serum selenium concentration. This association was modified by rs1050450 (C>T) in GPX1 (P(interaction) = 0.03), with carriers of one or two T alleles having a significantly reduced OR of 0.87 (95% CI, 0.76-0.99). Furthermore, there was an association between rs7579 genotype in SEPP1 and prostate cancer risk (OR, 1.72; 95% CI, 0.99-2.98).
  
  
  CONCLUSIONS
  Our results support a role of selenium and polymorphisms in selenoenzymes in prostate cancer etiology, which warrants confirmation in future studies.
  
  
  CONCLUSIONS
  These findings might help to explain biological effects of selenium in prostate cancer development in order to overcome inconsistencies arising from former studies.
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Astrid
authors.initials: A
authors.lastname: Steinbrecher
authors.forename: Catherine
authors.initials: C
authors.lastname: Méplan
authors.forename: John
authors.initials: J
authors.lastname: Hesketh
authors.forename: Lutz
authors.initials: L
authors.lastname: Schomburg
authors.forename: Tobias
authors.initials: T
authors.lastname: Endermann
authors.forename: Eugène
authors.initials: E
authors.lastname: Jansen
authors.forename: Björn
authors.initials: B
authors.lastname: Akesson
authors.forename: Sabine
authors.initials: S
authors.lastname: Rohrmann
authors.forename: Jakob
authors.initials: J
authors.lastname: Linseisen
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005060:Europe; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000097:blood* / Q000235:genetics*; D012307:Risk Factors; D012643:Selenium / Q000097:blood*; D051140:Selenoproteins / Q000097:blood / Q000235:genetics*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D051140:Selenoproteins; C486484:GPX3 protein, human; D005979:Glutathione Peroxidase; D012643:Selenium