Defining the optimal selenium dose for prostate cancer risk reduction: Insights from the u-shaped relationship between selenium status, DNA damage, and apoptosis

Emily C. Chiang, Shuren Shen, Seema S. Kengeri, Huiping Xu, Gerald F. Combs, J. Steven Morris, David G. Bostwick, David J. Waters

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

Our work in dogs has revealed a U-shaped dose response between selenium status and prostatic DNA damage that remarkably parallels the relationship between dietary selenium and prostate cancer risk in men, suggesting that more selenium is not necessarily better. Herein, we extend this canine work to show that the selenium dose that minimizes prostatic DNA damage also maximizes apoptosis-a cancer-suppressing death switch used by prostatic epithelial cells. These provocative findings suggest a new line of thinking about how selenium can reduce cancer risk. Mid-range selenium status (.67-.92 ppm in toenails) favors a process we call "homeostatic housecleaning"-an upregulated apoptosis that preferentially purges damaged prostatic cells. Also, the U-shaped relationship provides valuable insight into stratifying individuals as selenium-responsive or selenium-refractory, based upon the likelihood of reducing their cancer risk by additional selenium. By studying elderly dogs, the only non-human animal model of spontaneous prostate cancer, we have established a robust experimental approach bridging the gap between laboratory and human studies that can help to define the optimal doses of cancer preventives for large-scale human trials. Moreover, our observations bring much needed clarity to the null results of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) and set a new research priority: testing whether men with low, suboptimal selenium levels less than 0.8 ppm in toenails can achieve cancer risk reduction through daily supplementation.

Original languageEnglish (US)
Pages (from-to)285-300
Number of pages16
JournalDose-Response
Volume8
Issue number3
DOIs
StatePublished - 2010
Externally publishedYes

Keywords

  • Cancer prevention
  • Dietary supplements
  • Dog
  • Non-linear
  • Personalized medicine

ASJC Scopus subject areas

  • Toxicology
  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis
  • Chemical Health and Safety

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