Insertion of an SVA-E retrotransposon into the CASP8 gene is associated with protection against prostate cancer.
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AuthorsStacey, Simon N
Gudjonsson, Sigurjon A
Halldorsson, Bjarni V
Agnarsson, Bjarni A
Benediktsdottir, Kristrun R
Aben, Katja K H
Vermeulen, Sita H
Cremers, Ruben G
Helfand, Brian T
Cooper, Phillip R
Donovan, Jenny L
Hamdy, Freddie C
Jonasson, Jon G
Kristinsdottir, Anna M
Magnusson, Olafur T
Iordache, Paul D
Gudbjartsson, Daniel F
Barkardottir, Rosa B
Einarsson, Gudmundur V
Mates, Ioan N
Neal, David E
Catalona, William J
Mayordomo, José I
Kiemeney, Lambertus A
MetadataShow full item record
CitationHum. Mol. Genet. 2016, 25 (5):1008-18
AbstractTranscriptional 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] (r(2) = 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)).
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RightsArchived with thanks to Human molecular genetics
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