Journal Article

DKFZ-2021-00987

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png KLK3 SNP-SNP interactions for prediction of prostate cancer aggressiveness.

Lin, H.-Y. ; Huang, P.-Y. ; Cheng, C.-H. ; Tung, H.-Y. ; Fang, Z. ; Berglund, A. E. ; Chen, A. ; French-Kwawu, J. ; Harris, D. ; Pow-Sang, J. ; Yamoah, K. ; Cleveland, J. L. ; Awasthi, S. ; Rounbehler, R. J. ; Gerke, T. ; Dhillon, J. ; Eeles, R. ; Kote-Jarai, Z. ; Muir, K. ; UKGPCS collaborators (Collaboration Author) ; Schleutker, J. ; Pashayan, N. ; APCB (Collaboration Author) ; Neal, D. E. ; Nielsen, S. F. ; Nordestgaard, B. G. ; Gronberg, H. ; Wiklund, F. ; Giles, G. G. ; Haiman, C. A. ; Travis, R. C. ; Stanford, J. L. ; Kibel, A. S. ; Cybulski, C. ; Khaw, K.-T. ; Maier, C. ; Thibodeau, S. N. ; Teixeira, M. R. ; Cannon-Albright, L. ; Brenner, H.DKFZ* ; Kaneva, R. ; Pandha, H. ; consortium, P. (Collaboration Author) ; Srinivasan, S. ; Clements, J. ; Batra, J. ; Park, J. Y. ; Eeles, R. ; Kote-Jarai, Z. ; Muir, K. ; Clements, J. ; Batra, J. ; Lin, H.-Y. ; Eeles, R. ; Kote-Jarai, Z. ; Muir, K. ; Schleutker, J. ; Pashayan, N. ; Neal, D. E. ; Nielsen, S. F. ; Nordestgaard, B. G. ; Gronberg, H. ; Wiklund, F. ; Giles, G. G. ; Haiman, C. A. ; Travis, R. C. ; Stanford, J. L. ; Kibel, A. S. ; Cybulski, C. ; Khaw, K.-T. ; Maier, C. ; Thibodeau, S. N. ; Teixeira, M. R. ; Cannon-Albright, L. ; Brenner, H.DKFZ* ; Kaneva, R. ; Pandha, H.

2021
Macmillan Publishers Limited, part of Springer Nature [London]

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Please use a persistent id in citations: doi: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 × 10-9) and 3145 (P < 1 × 10-5) 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.

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Contributing Institute(s):

1. C070 Klinische Epidemiologie und Alternf. (C070)
2. Präventive Onkologie (C120)
3. DKTK HD zentral (HD01)

Research Program(s):

1. 313 - Krebsrisikofaktoren und Prävention (POF4-313) (POF4-313)

Appears in the scientific report 2021

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