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KLK3 SNP-SNP interactions for prediction of prostate cancer aggressiveness
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(2021) KLK3 SNP-SNP interactions for prediction of prostate cancer aggressiveness. Scientific Reports, 11 (1). 9264. doi:10.1038/s41598-021-85169-7 ISSN 2045-2322.
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Official URL: https://doi.org/10.1038/s41598-021-85169-7
Abstract
Risk classification for prostate cancer (PCa) aggressiveness and underlying mechanisms remain inadequate. Interactions between single nucleotide polymorphisms (SNPs) may provide a solution to fill these gaps. To identify SNP-SNP interactions in the four pathways (the angiogenesis-, mitochondria-, miRNA-, and androgen metabolism-related pathways) associated with PCa aggressiveness, we tested 8587 SNPs for 20,729 cases from the PCa consortium. We identified 3 KLK3 SNPs, and 1083 (P < 3.5 × 10 ) and 3145 (P < 1 × 10 ) SNP-SNP interaction pairs significantly associated with PCa aggressiveness. These SNP pairs associated with PCa aggressiveness were more significant than each of their constituent SNP individual effects. The majority (98.6%) of the 3145 pairs involved KLK3. The 3 most common gene-gene interactions were KLK3-COL4A1:COL4A2, KLK3-CDH13, and KLK3-TGFBR3. Predictions from the SNP interaction-based polygenic risk score based on 24 SNP pairs are promising. The prevalence of PCa aggressiveness was 49.8%, 21.9%, and 7.0% for the PCa cases from our cohort with the top 1%, middle 50%, and bottom 1% risk profiles. Potential biological functions of the identified KLK3 SNP-SNP interactions were supported by gene expression and protein-protein interaction results. Our findings suggest KLK3 SNP interactions may play an important role in PCa aggressiveness.
Item Type: | Journal Article | ||||||
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Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School | ||||||
SWORD Depositor: | Library Publications Router | ||||||
Journal or Publication Title: | Scientific Reports | ||||||
Publisher: | Nature Publishing Group | ||||||
ISSN: | 2045-2322 | ||||||
Official Date: | 29 April 2021 | ||||||
Dates: |
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Volume: | 11 | ||||||
Number: | 1 | ||||||
Article Number: | 9264 | ||||||
DOI: | 10.1038/s41598-021-85169-7 | ||||||
Status: | Peer Reviewed | ||||||
Publication Status: | Published | ||||||
Access rights to Published version: | Open Access (Creative Commons) |
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