Insertion of an SVA-E retrotransposon into the CASP8 gene is associated with protection against prostate cancer

Simon N. Stacey*, Birte Kehr, Julius Gudmundsson, Florian Zink, Aslaug Jonasdottir, Sigurjon A. Gudjonsson, Asgeir Sigurdsson, Bjarni V. Halldorsson, Bjarni A. Agnarsson, Kristrun R. Benediktsdottir, Katja K.H. Aben, Sita H. Vermeulen, Ruben G. Cremers, Angeles Panadero, Brian T. Helfand, Phillip R. Cooper, Jenny L. Donovan, Freddie C. Hamdy, Viorel Jinga, Ichiro OkamotoJon G. Jonasson, Laufey Tryggvadottir, Hrefna Johannsdottir, Anna M. Kristinsdottir, Gisli Masson, Olafur T. Magnusson, Paul D. Iordache, Agnar Helgason, Hannes Helgason, Patrick Sulem, Daniel F. Gudbjartsson, Augustine Kong, Eirikur Jonsson, Rosa B. Barkardottir, Gudmundur V. Einarsson, Thorunn Rafnar, Unnur Thorsteinsdottir, Ioan N. Mates, David E. Neal, William J. Catalona, José I. Mayordomo, Lambertus A. Kiemeney, Gudmar Thorleifsson, Kari Stefansson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


Transcriptional and splicing anomalies have been observed in intron 8 of the CASP8 gene (encoding procaspase-8) in association with cutaneous basal-cell carcinoma (BCC) and linked to a germline SNP rs700635. Here, we show that the rs700635[C] allele, which is associated with increased risk of BCC and breast cancer, is protective against prostate cancer [odds ratio (OR) = 0.91, P = 1.0 × 10-6]. rs700635[C] is also associated with failures to correctly splice out CASP8 intron 8 in breast and prostate tumours and in corresponding normal tissues. Investigation of rs700635[C] carriers revealed that they have a human-specific short interspersed element-variable number of tandem repeat-Alu (SINE-VNTR-Alu), subfamily-E retrotransposon (SVA-E) inserted into CASP8 intron 8. The SVA-E shows evidence of prior activity, because it has transduced some CASP8 sequences during subsequent retrotransposition events. Whole-genome sequence (WGS) data were used to tag the SVA-E with a surrogate SNP rs1035142[T] (r2 = 0.999), which showed associations with both the splicing anomalies (P = 6.5 × 10-32) and with protection against prostate cancer (OR = 0.91, P = 3.8 × 10-7).

Original languageEnglish
Pages (from-to)1008-1018
Number of pages11
JournalHuman Molecular Genetics
Issue number5
Publication statusPublished - 1 Mar 2016

Bibliographical note

Publisher Copyright:
© The Author 2016. Published by Oxford University Press. All rights reserved.


Dive into the research topics of 'Insertion of an SVA-E retrotransposon into the CASP8 gene is associated with protection against prostate cancer'. Together they form a unique fingerprint.

Cite this