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KLK3 SNP-SNP interactions for prediction of prostate cancer aggressiveness.
Lin, Hui-Yi; Huang, Po-Yu; Cheng, Chia-Ho; Tung, Heng-Yuan; Fang, Zhide; Berglund, Anders E; Chen, Ann; French-Kwawu, Jennifer; Harris, Darian; Pow-Sang, Julio; Yamoah, Kosj; Cleveland, John L; Awasthi, Shivanshu; Rounbehler, Robert J; Gerke, Travis; Dhillon, Jasreman; Eeles, Rosalind; Kote-Jarai, Zsofia; Muir, Kenneth; Schleutker, Johanna; Pashayan, Nora; Neal, David E; Nielsen, Sune F; Nordestgaard, Børge G; Gronberg, Henrik; Wiklund, Fredrik; Giles, Graham G; Haiman, Christopher A; Travis, Ruth C; Stanford, Janet L; Kibel, Adam S; Cybulski, Cezary; Khaw, Kay-Tee; Maier, Christiane; Thibodeau, Stephen N; Teixeira, Manuel R; Cannon-Albright, Lisa; Brenner, Hermann; Kaneva, Radka; Pandha, Hardev; Srinivasan, Srilakshmi; Clements, Judith; Batra, Jyotsna; Park, Jong Y.
Afiliação
  • Lin HY; Biostatistics Program, School of Public Health, Louisiana State University Health Sciences Center, New Orleans, LA, 70112, USA. hlin1@lsuhsc.edu.
  • Huang PY; Computational Intelligence Technology Center, Industrial Technology Research Institute, Hsinchu, Taiwan.
  • Cheng CH; Department of Biostatistics and Bioinformatics, Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, USA.
  • Tung HY; Biostatistics Program, School of Public Health, Louisiana State University Health Sciences Center, New Orleans, LA, 70112, USA.
  • Fang Z; Biostatistics Program, School of Public Health, Louisiana State University Health Sciences Center, New Orleans, LA, 70112, USA.
  • Berglund AE; Department of Biostatistics and Bioinformatics, Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, USA.
  • Chen A; Department of Biostatistics and Bioinformatics, Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, USA.
  • French-Kwawu J; Biostatistics Program, School of Public Health, Louisiana State University Health Sciences Center, New Orleans, LA, 70112, USA.
  • Harris D; Biostatistics Program, School of Public Health, Louisiana State University Health Sciences Center, New Orleans, LA, 70112, USA.
  • Pow-Sang J; Department of Genitourinary Oncology, Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, USA.
  • Yamoah K; Department of Radiation Oncology, Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, USA.
  • Cleveland JL; Department of Tumor Biology, Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, USA.
  • Awasthi S; Department of Cancer Epidemiology, Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, USA.
  • Rounbehler RJ; Department of Tumor Biology, Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, USA.
  • Gerke T; Department of Cancer Epidemiology, Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, USA.
  • Dhillon J; Department of Pathology, Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, USA.
  • Eeles R; The Institute of Cancer Research, London, SM2 5NG, UK.
  • Kote-Jarai Z; Royal Marsden NHS Foundation Trust, London, SW3 6JJ, UK.
  • Muir K; The Institute of Cancer Research, London, SM2 5NG, UK.
  • Schleutker J; Warwick Medical School, University of Warwick, Coventry, UK.
  • Neal DE; Department of Medical Genetics, Genomics, Laboratory Division, Turku University Hospital, PO Box 52, 20521, Turku, Finland.
  • Nielsen SF; Department of Applied Health Research, University College London, London, UK.
  • Nordestgaard BG; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Strangeways Laboratory, Worts Causeway, Cambridge, CB1 8RN, UK.
  • Gronberg H; Department of Applied Health Research, University College London, London, WC1E 7HB, UK.
  • Giles GG; Nuffield Department of Surgical Sciences, University of Oxford, Room 6603, Level 6, John Radcliffe Hospital, Headley Way, Headington, Oxford, OX3 9DU, UK.
  • Haiman CA; Department of Oncology, University of Cambridge, Addenbrooke's Hospital, Hills Road, Box 279, Cambridge, CB2 0QQ, UK.
  • Travis RC; Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark.
  • Stanford JL; Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, 2200, Copenhagen, Denmark.
  • Kibel AS; Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark.
  • Cybulski C; Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, 2200, Copenhagen, Denmark.
  • Khaw KT; Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
  • Maier C; Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
  • Thibodeau SN; Cancer Epidemiology Division, Cancer Council Victoria, 615 St Kilda Road, Melbourne, VIC, 3004, Australia.
  • Teixeira MR; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Grattan Street, Parkville, VIC, 3010, Australia.
  • Cannon-Albright L; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, 3168, Australia.
  • Brenner H; Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, 90015, USA.
  • Kaneva R; Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK.
  • Pandha H; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109-1024, USA.
  • Srinivasan S; Division of Urologic Surgery, Brigham and Womens Hospital, 75 Francis Street, Boston, MA, 02115, USA.
  • Clements J; Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
  • Batra J; Clinical Gerontology Unit, University of Cambridge, Cambridge, CB2 2QQ, UK.
  • Park JY; Humangenetik Tuebingen, Paul-Ehrlich-Str 23, 72076, Tuebingen, Germany.
Sci Rep ; 11(1): 9264, 2021 04 29.
Article em En | MEDLINE | ID: mdl-33927218
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-COL4A1COL4A2, 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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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Calicreínas / Antígeno Prostático Específico Idioma: En Ano de publicação: 2021 Tipo de documento: Article
Texto completo
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PubMed Links
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Calicreínas / Antígeno Prostático Específico Idioma: En Ano de publicação: 2021 Tipo de documento: Article