Interaction of NKX3.1 and SELENOP genotype with prostate cancer recurrence

Prostate. 2019 Apr;79(5):462-467. doi: 10.1002/pros.23752. Epub 2018 Dec 23.

Abstract

Background: NKX3.1 is a tumor suppressor frequently lost in prostate cancer. Previous studies by others indicated that the risks associated with reduced NKX3.1 levels can be enhanced by anti-oxidant supplementation. Selenium is an essential component of several proteins with anti-oxidant functions and lower levels of selenium have been associated with greater risk of prostate cancer. In contrast, participants of the select prostate cancer prevention trial were at increased risk of prostate cancer when supplemented with selenium when their baseline selenium levels were high.

Methods: In order to investigate whether there was an interaction between a functional polymorphism in NKX3.1 that results in less protein and selenium status with prostate cancer grade or outcome, plasma selenium levels and the genotypes of NKX3.1 and the selenium carrier protein SELENOP were determined from a cohort of men who underwent radical protatectomy.

Results: NKX3.1 and SELENOP genotypes were associated with a more aggressive prostate tumor grade at the time of prostatectomy, but there were no significant interactions of NKX3.1 genotype with either selenium status or SELENOP genotype. There was also a significant association between NKX3.1 genotype and prostate cancer recurrence, however this association was modified by SELENOP genotype, but not with plasma selenium levels.

Conclusions: These data indicate that the impact of selenium status on prostate cancer may be influenced by factors other than the amount of selenium in circulation.

Keywords: prostatectomy; selenium; selenoproteins.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cohort Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Homeodomain Proteins / genetics*
  • Humans
  • Kallikreins / blood
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / blood
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / pathology
  • Polymorphism, Single Nucleotide
  • Prospective Studies
  • Prostate-Specific Antigen / blood
  • Prostatectomy
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / surgery
  • Selenoprotein P / genetics*
  • Transcription Factors / genetics*

Substances

  • Homeodomain Proteins
  • NKX3-1 protein, human
  • SELENOP protein, human
  • Selenoprotein P
  • Transcription Factors
  • KLK3 protein, human
  • Kallikreins
  • Prostate-Specific Antigen