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Impaired Vitamin D Signaling Is Associated With Frequent Development of Renal Cell Tumor in End-stage Kidney Disease.

Authors
  • Docs, Janos1, 2
  • Banyai, Daniel1
  • Flasko, Tibor2
  • Szanto, Arpad1
  • Kovacs, Gyula3, 4
  • 1 Department of Urology, Medical School, University of Pecs, Pecs, Hungary. , (Hungary)
  • 2 Department of Urology, Medical School, University of Debrecen, Debrecen, Hungary. , (Hungary)
  • 3 Department of Urology, Medical School, University of Pecs, Pecs, Hungary [email protected] , (Hungary)
  • 4 Medical Faculty, Ruprecht-Karls-University, Heidelberg, Germany. , (Germany)
Type
Published Article
Journal
Anticancer Research
Publisher
International Institute of Anticancer Research
Publication Date
Nov 01, 2020
Volume
40
Issue
11
Pages
6525–6530
Identifiers
DOI: 10.21873/anticanres.14676
PMID: 33109593
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

End-stage kidney disease is characterized by chronic inflammation and frequent development of cancer. The level of circulating vitamin D is generally low in patients with end-stage renal disease (ESRD). Experimental studies have implicated the role of dysfunctional vitamin D metabolism in tumorigenesis. We analyzed the expression of vitamin D receptor (VDR), cytochrome P450 family 27 subfamily B member 1 (CYP27B1) and cytochrome P450 family 24 subfamily A member 1 (CYP24A1), the key genes involved in vitamin D signaling, in kidneys from patients with ESRD, tissue microarrays containing ESRD-associated renal cell tumors, as well as in their precursor lesions by immunohistochemistry. Kidneys from patients with ESRD showed strong structural rearrangement with only few tubules and epithelial cell groups embedded in fibrotic-inflammatory stroma. Only an estimated 1-3% of the epithelial cells showed positive staining with antibodies to VDR, CYP27B1 and CYP24A1, which contrasted with the 100%, 40-50% and 40-50% of positively stained cells, respectively, found in normal kidneys. Down-regulation of the vitamin D signaling proteins was found in patients with renal cancer, with the exception of tumors and their precursors occurring exclusively in ESRD. The significantly reduced activity of CYP27B1 in kidney from patients with ESRD explains the low level of circulating vitamin D. We suggest that the lack of anti-tumorigenic effect of vitamin D is a crucial factor in the frequent development of unique types of renal cell cancer in in patients with ESRD. Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

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