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Prostate cancer risk stratification improvement across multiple ancestries with new polygenic hazard score.
Huynh-Le, Minh-Phuong; Karunamuni, Roshan; Fan, Chun Chieh; Asona, Lui; Thompson, Wesley K; Martinez, Maria Elena; Eeles, Rosalind A; Kote-Jarai, Zsofia; Muir, Kenneth R; Lophatananon, Artitaya; Schleutker, Johanna; Pashayan, Nora; Batra, Jyotsna; Grönberg, Henrik; Neal, David E; Nordestgaard, Børge G; Tangen, Catherine M; MacInnis, Robert J; Wolk, Alicja; Albanes, Demetrius; Haiman, Christopher A; Travis, Ruth C; Blot, William J; Stanford, Janet L; Mucci, Lorelei A; West, Catharine M L; Nielsen, Sune F; Kibel, Adam S; Cussenot, Olivier; Berndt, Sonja I; Koutros, Stella; Sørensen, Karina Dalsgaard; Cybulski, Cezary; Grindedal, Eli Marie; Menegaux, Florence; Park, Jong Y; Ingles, Sue A; Maier, Christiane; Hamilton, Robert J; Rosenstein, Barry S; Lu, Yong-Jie; Watya, Stephen; Vega, Ana; Kogevinas, Manolis; Wiklund, Fredrik; Penney, Kathryn L; Huff, Chad D; Teixeira, Manuel R; Multigner, Luc; Leach, Robin J.
  • Huynh-Le MP; Radiation Oncology, George Washington University, Washington, DC, USA.
  • Karunamuni R; Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA.
  • Fan CC; Center for Multimodal Imaging and Genetics, University of California San Diego, La Jolla, CA, USA.
  • Asona L; Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA.
  • Thompson WK; Center for Multimodal Imaging and Genetics, University of California San Diego, La Jolla, CA, USA.
  • Martinez ME; Center for Multimodal Imaging and Genetics, University of California San Diego, La Jolla, CA, USA.
  • Eeles RA; Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA.
  • Kote-Jarai Z; Division of Biostatistics and Halicioglu Data Science Institute, University of California San Diego, La Jolla, CA, USA.
  • Muir KR; Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA, USA.
  • Lophatananon A; University of California San Diego, Moores Cancer Center, Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, 92093-0012, USA.
  • Schleutker J; The Institute of Cancer Research, London, SM2 5NG, UK.
  • Pashayan N; Royal Marsden NHS Foundation Trust, London, SW3 6JJ, UK.
  • Batra J; The Institute of Cancer Research, London, SM2 5NG, UK.
  • Grönberg H; Division of Population Health, Health Services Research and Primary Care, University of Manchester, Oxford Road, Manchester, M13 9PL, UK.
  • Neal DE; Division of Population Health, Health Services Research and Primary Care, University of Manchester, Oxford Road, Manchester, M13 9PL, UK.
  • Nordestgaard BG; Institute of Biomedicine, University of Turku, Turku, Finland.
  • Tangen CM; Department of Medical Genetics, Genomics, Laboratory Division, Turku University Hospital, PO Box 52, 20521, Turku, Finland.
  • MacInnis RJ; Department of Applied Health Research, University College London, London, WC1E 7HB, UK.
  • Wolk A; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Strangeways Laboratory, Worts Causeway, Cambridge, CB1 8RN, UK.
  • Albanes D; Australian Prostate Cancer Research Centre-Qld, Institute of Health and Biomedical Innovation and School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, 4059, Australia.
  • Haiman CA; Translational Research Institute, Brisbane, QLD, 4102, Australia.
  • Travis RC; Department of Medical Epidemiology and Biostatistics, Karolinska Institute, SE-171 77, Stockholm, Sweden.
  • Blot WJ; Nuffield Department of Surgical Sciences, University of Oxford, Room 6603, Level 6, John Radcliffe Hospital, Headley Way, Headington, Oxford, OX3 9DU, UK.
  • Stanford JL; University of Cambridge, Department of Oncology, Box 279, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ, UK.
  • Mucci LA; Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Cambridge, CB2 0RE, UK.
  • West CML; Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark.
  • Nielsen SF; Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, 2200, Copenhagen, Denmark.
  • Kibel AS; SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Cussenot O; Cancer Epidemiology Division, Cancer Council Victoria, 615 St Kilda Road, Melbourne, VIC, 3004, Australia.
  • Berndt SI; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Grattan Street, Parkville, VIC, 3010, Australia.
  • Koutros S; Department of Surgical Sciences, Uppsala University, 75185, Uppsala, Sweden.
  • Sørensen KD; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, 20892, USA.
  • Cybulski C; 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.
  • Grindedal EM; Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK.
  • Menegaux F; Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, 2525 West End Avenue, Suite 800, Nashville, TN, 37232, USA.
  • Park JY; International Epidemiology Institute, Rockville, MD, 20850, USA.
  • Ingles SA; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109-1024, USA.
  • Maier C; Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, 98195, USA.
  • Hamilton RJ; Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, 02115, USA.
  • Rosenstein BS; Division of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Radiotherapy Related Research, The Christie Hospital NHS Foundation Trust, Manchester, M13 9PL, UK.
  • Lu YJ; Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark.
  • Watya S; Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, 2200, Copenhagen, Denmark.
  • Vega A; Division of Urologic Surgery, Brigham and Womens Hospital, 75 Francis Street, Boston, MA, 02115, USA.
  • Kogevinas M; Sorbonne Universite, GRC n°5, AP-HP, Tenon Hospital, 4 rue de la Chine, F-45020, Paris, France.
  • Wiklund F; CeRePP, Tenon Hospital, F-75020, Paris, France.
  • Penney KL; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, 20892, USA.
  • Huff CD; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, 20892, USA.
  • Teixeira MR; Department of Molecular Medicine, Aarhus University Hospital, Palle Juul-Jensen Boulevard 99, 8200, Aarhus N, Denmark.
  • Multigner L; Department of Clinical Medicine, Aarhus University, DK, 8200, Aarhus N, Denmark.
  • Leach RJ; International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, 70-115, Szczecin, Poland.
Prostate Cancer Prostatic Dis ; 25(4): 755-761, 2022 04.
Article en En | MEDLINE | ID: mdl-35152271
ABSTRACT

BACKGROUND:

Prostate cancer risk stratification using single-nucleotide polymorphisms (SNPs) demonstrates considerable promise in men of European, Asian, and African genetic ancestries, but there is still need for increased accuracy. We evaluated whether including additional SNPs in a prostate cancer polygenic hazard score (PHS) would improve associations with clinically significant prostate cancer in multi-ancestry datasets.

METHODS:

In total, 299 SNPs previously associated with prostate cancer were evaluated for inclusion in a new PHS, using a LASSO-regularized Cox proportional hazards model in a training dataset of 72,181 men from the PRACTICAL Consortium. The PHS model was evaluated in four testing datasets African ancestry, Asian ancestry, and two of European Ancestry-the Cohort of Swedish Men (COSM) and the ProtecT study. Hazard ratios (HRs) were estimated to compare men with high versus low PHS for association with clinically significant, with any, and with fatal prostate cancer. The impact of genetic risk stratification on the positive predictive value (PPV) of PSA testing for clinically significant prostate cancer was also measured.

RESULTS:

The final model (PHS290) had 290 SNPs with non-zero coefficients. Comparing, for example, the highest and lowest quintiles of PHS290, the hazard ratios (HRs) for clinically significant prostate cancer were 13.73 [95% CI 12.43-15.16] in ProtecT, 7.07 [6.58-7.60] in African ancestry, 10.31 [9.58-11.11] in Asian ancestry, and 11.18 [10.34-12.09] in COSM. Similar results were seen for association with any and fatal prostate cancer. Without PHS stratification, the PPV of PSA testing for clinically significant prostate cancer in ProtecT was 0.12 (0.11-0.14). For the top 20% and top 5% of PHS290, the PPV of PSA testing was 0.19 (0.15-0.22) and 0.26 (0.19-0.33), respectively.

CONCLUSIONS:

We demonstrate better genetic risk stratification for clinically significant prostate cancer than prior versions of PHS in multi-ancestry datasets. This is promising for implementing precision-medicine approaches to prostate cancer screening decisions in diverse populations.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / Antígeno Prostático Específico Tipo de estudio: Diagnostic_studies / Etiology_studies / Prognostic_studies / Risk_factors_studies / Screening_studies Límite: Humans / Male Idioma: En Año: 2022 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / Antígeno Prostático Específico Tipo de estudio: Diagnostic_studies / Etiology_studies / Prognostic_studies / Risk_factors_studies / Screening_studies Límite: Humans / Male Idioma: En Año: 2022 Tipo del documento: Article