Open Access Repository

A rare variant in EZH2 is associated with prostate cancer risk

Raspin, K ORCID: 0000-0001-8463-6820, Fitzgerald, LM ORCID: 0000-0002-6882-2698, Marthick, JR, Field, MA, Malley, RC ORCID: 0000-0002-3289-5270, Banks, A, Donovan, S, Thomson, RJ, Foley, GR, Stanford, JL and Dickinson, JL ORCID: 0000-0003-4621-1703 2021 , 'A rare variant in EZH2 is associated with prostate cancer risk' , International Journal of Cancer , pp. 1-11 , doi: 10.1002/ijc.33584.

Full text not available from this repository.


Prostate cancer (PrCa) is highly heritable, and although rare variants contribute significantly to PrCa risk, few have been identified to date. Herein, whole-genomesequencing was performed in a large PrCa family featuring multiple affected relativesspanning several generations. A rare, predicted splice site EZH2 variant, rs78589034(G > A), was identified as segregating with disease in all but two individuals in thefamily, one of whom was affected with lymphoma and bowel cancer and a female relative. This variant was significantly associated with disease risk in combined familialand sporadic PrCa datasets (n = 1551; odds ratio [OR] = 3.55, P = 1.20 × 10−5).Transcriptome analysis was performed on prostate tumour needle biopsies availablefor two rare variant carriers and two wild-type cases. Although no allele-dependentdifferences were detected in EZH2 transcripts, a distinct differential gene expressionsignature was observed when comparing prostate tissue from the rare variant carrierswith the wild-type samples. The gene expression signature comprised known downstream targets of EZH2 and included the top-ranked genes, DUSP1, FOS, JUNB andEGR1, which were subsequently validated by qPCR. These data provide evidence thatrs78589034 is associated with increased PrCa risk in Tasmanian men and further,that this variant may be associated with perturbed EZH2 function in prostate tissue.Disrupted EZH2 function is a driver of tumourigenesis in several cancers, includingprostate, and is of significant interest as a therapeutic target.

Item Type: Article
Authors/Creators:Raspin, K and Fitzgerald, LM and Marthick, JR and Field, MA and Malley, RC and Banks, A and Donovan, S and Thomson, RJ and Foley, GR and Stanford, JL and Dickinson, JL
Keywords: genetic susceptibility, prostate cancer, rare genetic variants, transcriptome analysis
Journal or Publication Title: International Journal of Cancer
Publisher: Wiley-Liss
ISSN: 0020-7136
DOI / ID Number: 10.1002/ijc.33584
Copyright Information:

© 2021 Union for International Cancer Control.

Related URLs:
Item Statistics: View statistics for this item

Actions (login required)

Item Control Page Item Control Page