Selenium levels in human breast carcinoma tissue are associated with a common polymorphism in the gene for SELENOP (Selenoprotein P)

Authors: EKOUE, DEDE - University Of Illinois; ZAICHICK, SOFIA - University Of Illinois; VALYI-NAGY, KLARA - University Of Illinois; Picklo, Matthew; Lacher, Craig; HOSKINS, KENT - University Of Illinois; BONINI, MARCELO - University Of Illinois; DIAMOND, ALAN - University Of Illinois

Submitted to: Journal of Trace Elements in Medicine and Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/4/2016
Publication Date: 1/4/2017
Publication URL: https://handle.nal.usda.gov/10113/5832855
Citation: Ekoue, D.N., Zaichick, S., Valyi-Nagy, K., Picklo, M.J., Lacher, C.P., Hoskins, K., Bonini, M., Diamond, A.M. 2017. Selenium levels in human breast carcinoma tissue are associated with a common polymorphism in the gene for SELENOP (Selenoprotein P). Journal of Trace Elements in Medicine and Biology. 39:227-233.

Interpretive Summary: Breast cancer risk in some women is associated with genetic differences in enzymes and pathways that metabolize free radicals. In this work, we examined the interaction of genetic differences in the enzymes mitochondrial superoxide dismutase (MnSOD), glutathione peroxidase, and Sepp1 in breast tumors. Moreover, we examined if levels of selenium, an element necessary for glutathione peroxidase activity and transported by Sepp1, was related to these genetic differences. The data show that genetic differences in Sepp1, but not glutathione peroxidase, were responsible for the differing levels of Se in the breast tumor tissue. In addition, genetic differences in MnSOD, associated with elevated breast cancer risk, led to an increase MnSOD protein in the breast tumor samples. These data indicate that there are potential genetic changes in the metabolism of free radicals that increase the risk of breast tumors.

Technical Abstract: Selenium supplementation of the diets of rodents has consistently been shown to suppress mammary carcinogenesis and some, albeit not all, human epidemiological studies have indicated an inverse association between selenium and breast cancer risk. In order to better understand the role selenium plays in breast cancer, 30 samples of tumor tissue were obtained from women with breast cancer and analyzed for selenium concentration, the levels of several selenium-containing proteins and the levels of the MnSOD anti-oxidant protein. Polymorphisms within the genes for these same proteins were determined from DNA isolated from the tissue samples. There was a wide range of selenium in these tissues, ranging from 24 to 854 ng/gm. The selenium levels in the tissues were correlated to the genotype of the Sepp1 selenium carrier protein, but not to other proteins whose levels have been reported to be responsive to selenium availability, including GPx-1, Sep15 and SBP1. There was an association between a polymorphism in the gene for MnSOD and the levels of the encoded protein. These studies were the first to examine the relationship between selenium levels, genotypes and protein levels in human tissues. Furthermore, the obtained data provide evidence for the need to obtain data about the effects of selenium in breast cancer by examining samples from that particular tissue type.