Unknown

Dataset Information

0

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


ABSTRACT: 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] (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)).

SUBMITTER: Stacey SN 

PROVIDER: S-EPMC4754045 | BioStudies | 2016-01-01

REPOSITORIES: biostudies

Similar Datasets

2012-01-01 | S-EPMC3486173 | BioStudies
2009-01-01 | S-EPMC2775590 | BioStudies
2011-01-01 | S-EPMC3412178 | BioStudies
2016-01-01 | S-EPMC4967303 | BioStudies
2003-01-01 | S-EPMC1180407 | BioStudies
2011-01-01 | S-EPMC3153304 | BioStudies
2019-01-01 | S-EPMC6928650 | BioStudies
2012-01-01 | S-EPMC3287187 | BioStudies
2010-01-01 | S-EPMC2945828 | BioStudies
2018-01-01 | S-EPMC5831509 | BioStudies