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000168679 0247_ $$2doi$$a10.1038/s41598-021-85169-7
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000168679 1001_ $$aLin, Hui-Yi$$b0
000168679 245__ $$aKLK3 SNP-SNP interactions for prediction of prostate cancer aggressiveness.
000168679 260__ $$a[London]$$bMacmillan Publishers Limited, part of Springer Nature$$c2021
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000168679 520__ $$aRisk classification for prostate cancer (PCa) aggressiveness and underlying mechanisms remain inadequate. Interactions between single nucleotide polymorphisms (SNPs) may provide a solution to fill these gaps. To identify SNP-SNP interactions in the four pathways (the angiogenesis-, mitochondria-, miRNA-, and androgen metabolism-related pathways) associated with PCa aggressiveness, we tested 8587 SNPs for 20,729 cases from the PCa consortium. We identified 3 KLK3 SNPs, and 1083 (P < 3.5 × 10-9) and 3145 (P < 1 × 10-5) SNP-SNP interaction pairs significantly associated with PCa aggressiveness. These SNP pairs associated with PCa aggressiveness were more significant than each of their constituent SNP individual effects. The majority (98.6%) of the 3145 pairs involved KLK3. The 3 most common gene-gene interactions were KLK3-COL4A1:COL4A2, KLK3-CDH13, and KLK3-TGFBR3. Predictions from the SNP interaction-based polygenic risk score based on 24 SNP pairs are promising. The prevalence of PCa aggressiveness was 49.8%, 21.9%, and 7.0% for the PCa cases from our cohort with the top 1%, middle 50%, and bottom 1% risk profiles. Potential biological functions of the identified KLK3 SNP-SNP interactions were supported by gene expression and protein-protein interaction results. Our findings suggest KLK3 SNP interactions may play an important role in PCa aggressiveness.
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000168679 7001_ $$aHuang, Po-Yu$$b1
000168679 7001_ $$aCheng, Chia-Ho$$b2
000168679 7001_ $$aTung, Heng-Yuan$$b3
000168679 7001_ $$aFang, Zhide$$b4
000168679 7001_ $$aBerglund, Anders E$$b5
000168679 7001_ $$aChen, Ann$$b6
000168679 7001_ $$aFrench-Kwawu, Jennifer$$b7
000168679 7001_ $$aHarris, Darian$$b8
000168679 7001_ $$aPow-Sang, Julio$$b9
000168679 7001_ $$aYamoah, Kosj$$b10
000168679 7001_ $$aCleveland, John L$$b11
000168679 7001_ $$aAwasthi, Shivanshu$$b12
000168679 7001_ $$aRounbehler, Robert J$$b13
000168679 7001_ $$aGerke, Travis$$b14
000168679 7001_ $$aDhillon, Jasreman$$b15
000168679 7001_ $$aEeles, Rosalind$$b16
000168679 7001_ $$aKote-Jarai, Zsofia$$b17
000168679 7001_ $$aMuir, Kenneth$$b18
000168679 7001_ $$aUKGPCS collaborators$$b19$$eCollaboration Author
000168679 7001_ $$aSchleutker, Johanna$$b20
000168679 7001_ $$aPashayan, Nora$$b21
000168679 7001_ $$aAPCB$$b22$$eCollaboration Author
000168679 7001_ $$aNeal, David E$$b23
000168679 7001_ $$aNielsen, Sune F$$b24
000168679 7001_ $$aNordestgaard, Børge G$$b25
000168679 7001_ $$aGronberg, Henrik$$b26
000168679 7001_ $$aWiklund, Fredrik$$b27
000168679 7001_ $$aGiles, Graham G$$b28
000168679 7001_ $$aHaiman, Christopher A$$b29
000168679 7001_ $$aTravis, Ruth C$$b30
000168679 7001_ $$aStanford, Janet L$$b31
000168679 7001_ $$aKibel, Adam S$$b32
000168679 7001_ $$aCybulski, Cezary$$b33
000168679 7001_ $$aKhaw, Kay-Tee$$b34
000168679 7001_ $$aMaier, Christiane$$b35
000168679 7001_ $$aThibodeau, Stephen N$$b36
000168679 7001_ $$aTeixeira, Manuel R$$b37
000168679 7001_ $$aCannon-Albright, Lisa$$b38
000168679 7001_ $$0P:(DE-He78)90d5535ff896e70eed81f4a4f6f22ae2$$aBrenner, Hermann$$b39$$udkfz
000168679 7001_ $$aKaneva, Radka$$b40
000168679 7001_ $$aPandha, Hardev$$b41
000168679 7001_ $$aconsortium, PRACTICAL$$b42$$eCollaboration Author
000168679 7001_ $$aSrinivasan, Srilakshmi$$b43
000168679 7001_ $$aClements, Judith$$b44
000168679 7001_ $$aBatra, Jyotsna$$b45
000168679 7001_ $$aPark, Jong Y$$b46
000168679 7001_ $$aEeles, Rosalind$$b47
000168679 7001_ $$aKote-Jarai, Zsofia$$b48
000168679 7001_ $$aMuir, Kenneth$$b49
000168679 7001_ $$aClements, Judith$$b50
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000168679 7001_ $$aMuir, Kenneth$$b55
000168679 7001_ $$aSchleutker, Johanna$$b56
000168679 7001_ $$aPashayan, Nora$$b57
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000168679 7001_ $$aNielsen, Sune F$$b59
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000168679 7001_ $$aWiklund, Fredrik$$b62
000168679 7001_ $$aGiles, Graham G$$b63
000168679 7001_ $$aHaiman, Christopher A$$b64
000168679 7001_ $$aTravis, Ruth C$$b65
000168679 7001_ $$aStanford, Janet L$$b66
000168679 7001_ $$aKibel, Adam S$$b67
000168679 7001_ $$aCybulski, Cezary$$b68
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000168679 7001_ $$aThibodeau, Stephen N$$b71
000168679 7001_ $$aTeixeira, Manuel R$$b72
000168679 7001_ $$aCannon-Albright, Lisa$$b73
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000168679 7001_ $$aKaneva, Radka$$b75
000168679 7001_ $$aPandha, Hardev$$b76
000168679 773__ $$0PERI:(DE-600)2615211-3$$a10.1038/s41598-021-85169-7$$gVol. 11, no. 1, p. 9264$$n1$$p9264$$tScientific reports$$v11$$x2045-2322$$y2021
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