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Selenium and Cancer: A Story that Should not be Forgotten-Insights from Genomics

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Advances in Nutrition and Cancer

Part of the book series: Cancer Treatment and Research ((CTAR,volume 159))

Abstract

Selenium (Se) is an essential micronutrient that is incorporated into selenoproteins. Although epidemiological studies suggest that low Se intake is associated with increased risk of various cancers, the results of supplementation trials have been confusing. These conflicting results may be due to different baseline Se status and/or genetic factors. In addition, mechanistic links between Se intake, selenoproteins and carcinogenesis are not clear. In this article, we discuss the functional significance of single-nucleotide polymorphisms (SNP) in selenoprotein genes and the evidence as to whether or not they influence risk of colorectal, prostate, lung or breast cancers. Both in vitro and in vivo studies have shown that a small number of SNPs in genes encoding glutathione peroxidases 1 and 4, selenoprotein P, selenoprotein S and 15-kDa selenoprotein have functional consequences. Data from case–control studies suggest that a variant at codon 198 in glutathione peroxidase 1 influences the effect of Se status on prostate cancer and risk, and it has also been associated with breast cancer and lung cancer risk, whereas variants in glutathione peroxidase 4, selenoprotein P and selenoprotein S may influence the risk of colorectal cancer. In addition, the results of gene microarray (transcriptomic) studies have identified novel selenoprotein biomarkers of Se status and novel downstream Se-targeted pathways. The work highlights the need to take baseline Se status and genetic factors into account in the design of future intervention trials.

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Abbreviations

SNP:

Single-nucleotide polymorphisms

GPX:

Glutathione peroxidase

TR:

Thioredoxin reductase

Sec:

Selenocysteine

SECIS:

Selenocysteine insertion sequence

Sel:

Selenoprotein

SePP:

Selenoprotein P

CRC:

Colorectal cancer

GWAS:

Genome-wide association studies

mTOR:

Mammalian target of rapamycin

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Acknowledgements

CM is supported by the Biotechnology and Biological Sciences Research Council (grant BB/H011471/1). Work in JEH’s laboratory has been supported by Biotechnology and Biological Sciences Research Council, Food Standards Agency, Wellcome Trust, European Union, World Cancer Research Fund and Newcastle Healthcare Charity.

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Authors and Affiliations

  1. Institute for Cell and Molecular Biosciences and Human Nutrition Research Centre, Newcastle University, Newcastle-upon-Tyne, NE2 4HH, UK

    Catherine Méplan & John Hesketh

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  1. Catherine Méplan
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  2. John Hesketh
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Correspondence to John Hesketh .

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Editors and Affiliations

  1. Dept. of Biochemistry and Biophysics, Second University of Naples, Naples, Italy

    Vincenzo Zappia

  2. Clinical and Experimental Medicine, University of Naples "Federico II", Naples, Italy

    Salvatore Panico

  3. Institute of Food Sciences National Research Council, Avellino, Italy

    Gian Luigi Russo

  4. Dept. of Experimental Oncology, National Cancer Institute, Naples, Italy

    Alfredo Budillon

  5. Dept. of Biochemistry and Biophysics, Second University of Naples, Naples, Italy

    Fulvio Della Ragione

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Méplan, C., Hesketh, J. (2014). Selenium and Cancer: A Story that Should not be Forgotten-Insights from Genomics. In: Zappia, V., Panico, S., Russo, G., Budillon, A., Della Ragione, F. (eds) Advances in Nutrition and Cancer. Cancer Treatment and Research, vol 159. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-38007-5_9

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  • DOI: https://doi.org/10.1007/978-3-642-38007-5_9

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