title: Selenoprotein P genetic variants and mrna expression, circulating selenium, and prostate cancer risk and survival.
abstract: BACKGROUND
  Low levels of selenium have been associated with increased risk of prostate cancer (PCa). Selenoprotein P is the most abundant selenoprotein in serum and delivers ten selenocysteine residues to tissues. Variation in the selenoprotein P gene (SEPP1) may influence PCa development or modify the effects of selenium. We examined the association of SEPP1 single nucleotide polymorphisms (SNPs) with PCa risk and survival, and tested for interactions.
  
  
  METHODS
  The Physicians' Health Study (PHS) is a prospective cohort of 22,071 US physicians; we utilized a nested case-control study of 1,352 PCa cases and 1,382 controls. We assessed four SNPs capturing common variation within the SEPP1 locus. In a subset of men (n = 80), we evaluated SEPP1 mRNA expression in tumors.
  
  
  RESULTS
  Two SNPs were significantly associated with PCa risk. For rs11959466, each T allele increased risk (odds ratio (OR) = 1.31; 95% confidence interval (CI): 1.02,1.69; P(trend)  = 0.03). For rs13168440, the rare homozygote genotype decreased risk compared to the common homozygote (OR = 0.56, 95% CI: 0.33, 0.96). Moreover, there was a significant interaction of rs13168440 with plasma selenium; increasing selenium levels were associated with decreased PCa risk only among men with the minor allele (P(interaction)  = 0.01). SEPP1 expression was significantly lower in men with lethal PCa than long-term survivors.
  
  
  CONCLUSIONS
  SEPP1 genetic variation was associated with PCa incidence; replication of these results in an independent dataset is necessary. These findings further support a causal link between selenium and PCa, and suggest that the effect of selenium may differ by genetics.
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA. kpenney@hsph.harvard.edu
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Penney
authors.forename: Haojie
authors.initials: H
authors.lastname: Li
authors.forename: Lorelei A
authors.initials: LA
authors.lastname: Mucci
authors.forename: Massimo
authors.initials: M
authors.lastname: Loda
authors.forename: Howard D
authors.initials: HD
authors.lastname: Sesso
authors.forename: Meir J
authors.initials: MJ
authors.lastname: Stampfer
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics* / Q000401:mortality; D012333:RNA, Messenger / Q000378:metabolism*; D012307:Risk Factors; D012643:Selenium / Q000097:blood*; D051149:Selenoprotein P / Q000235:genetics*; D016019:Survival Analysis
chemical_list: D012333:RNA, Messenger; D051149:Selenoprotein P; D012643:Selenium