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Title: Correlations of SELENOF and SELENOP genotypes with serum selenium levels and prostate cancer

Author
item EKOUE, DEDE - University Of Illinois
item ANSONG, EMMANUEL - University Of Illinois
item LI, LIU - University Of Illinois
item MACIAS, VIRGILIA - University Of Illinois
item DEATON, RYAN - University Of Illinois
item Lacher, Craig
item Picklo, Matthew
item NONN, LARISA - University Of Illinois
item GANN, PETER - University Of Illinois
item KAJDACSY-BALLA, ANDRE - University Of Illinois
item FREEMAN, VINCENT - University Of Illinois
item DIAMOND, ALAN - University Of Illinois

Submitted to: Journal of the National Cancer Institute
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/11/2017
Publication Date: 3/1/2018
Citation: Ekoue, D.N., Ansong, E., Li, L., Macias, V., Deaton, R., Lacher, C.P., Picklo, M.J., Nonn, L., Gann, P.H., Kajdacsy-Balla, A., Freeman, V.L., Diamond, A.M. 2018. Correlations of SELENOF and SELENOP genotypes with serum selenium levels and prostate cancer. Journal of the National Cancer Institute. 78(4):279-288. https://doi.org/10.1002/pros.23471.
DOI: https://doi.org/10.1002/pros.23471

Interpretive Summary: Differences in proteins called seleno-proteins may link prostate cancer risk and race. In this work, we studied the biology of a seleno-protein call SelenoF that is located in different parts of the cell in tumor cells versus healthy cells. SelenoF levels are dramatically reduced in prostate cancer cells relative to adjacent healthy benign tissue and are lower in the tumors derived from African American men as compared to tumors obtained from Caucasians. Our studies showed genetic differences for the SelenoF gene and lower selenium levels in African Americans as compared to Caucasians. SelenoF genotypes were associated with a higher histological grade of the tumor as were higher selenium levels. Polymorphisms in the selenium carrier protein SelenoP were associated with both higher serum prostate specific antigen (PSA) levels. These results indicate that there may be an interaction between selenium status and seleno-protein genotypes that contribute to the disparity in prostate cancer incidence and outcome experienced by African Americans.

Technical Abstract: Studies were conducted in order to investigate whether there were relationships among the genotype of selenoproteins implicated in increased cancer risk, selenium status and race. Initial efforts focused on the SELENOF protein which is cytoplasmic in human prostate cancer cell lines and tumor tissue, but shown here to reside in the outer cell membrane in benign epithelial cells of prostate glands. SELENOF levels are dramatically reduced in prostate cancer relative to adjacent benign tissue and are lower in the tumors derived from African American men as compared to tumors obtained from Caucasians. Analyzing sera and DNA from participants of the Chicago-based Adiposity Study Cohort, the previously reported dramatic difference in the distribution of functional polymorphisms in the SELENOF gene was confirmed and lower selenium levels were observed in African Americans as compared to Caucasians. SELENOF genotypes were associated with higher histological grade of the tumor as were higher selenium levels. Polymorphisms in the selenium carrier protein SELENOP was also examined for associations between genotype and clinical features, and shown to be associated with both higher serum PSA levels and biochemical failure. These results indicate that there may be an interaction between selenium status and selenoprotein genotypes that contribute to the disparity in prostate cancer incidence and outcome experienced by African Americans.