Publikationsdatum:
2016-02-16
Beschreibung:
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 x 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 x 10 –32 ) and with protection against prostate cancer (OR = 0.91, P = 3.8 x 10 –7 ).
Print ISSN:
0964-6906
Digitale ISSN:
1460-2083
Thema:
Biologie
,
Medizin
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