Single nucleotide polymorphisms of 17beta-hydroxysteroid dehydrogenase type 7 gene: mechanism of estramustine-related adverse reactions?

Int J Urol. 2009 Oct;16(10):836-41. doi: 10.1111/j.1442-2042.2009.02374.x. Epub 2009 Sep 3.

Abstract

Objectives: To investigate the influence of single nucleotide polymorphisms (SNP) on transcription of the 17beta-hydroxysteroid dehydrogenase (HSD17B7) gene.

Methods: Luciferase reporter genes containing a 5'-flanking of the HSD17B7 gene, as well as the sequence around the SNP, were transfected into LNCaP and DU145 cells. Then, luciferase assays were carried out.

Results: The presence of the G allele resulted in an increase of transcriptional activity derived from the 5'-flanking region of the HSD17B7 gene by 270% and 370% in LNCaP and DU145 cells, respectively. Transcriptional activity of the HSD17B7 gene containing the G allele was higher than that of the C allele.

Conclusions: The transcriptional activity of the HSD17B7 gene containing the G allele is higher than that of the C allele. This difference in HSD17B7 expression may regulate the risk of peripheral edema as an adverse reaction induced by estramustine phosphate sodium.

MeSH terms

  • 17-Hydroxysteroid Dehydrogenases / genetics*
  • Antineoplastic Agents, Hormonal / adverse effects*
  • Edema / chemically induced*
  • Edema / genetics*
  • Estramustine / adverse effects*
  • Humans
  • Polymorphism, Single Nucleotide*
  • Transcription, Genetic
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents, Hormonal
  • Estramustine
  • 17-Hydroxysteroid Dehydrogenases
  • 3 (or 17)-beta-hydroxysteroid dehydrogenase