| Title: |
Polygenic hazard score is associated with prostate cancer in multi-ethnic populations |
| Authors: |
Huynh-Le, Minh-Phuong; Fan, Chun Chieh; Karunamuni, Roshan; Thompson, Wesley; Martinez, Maria Elena; Eeles, Rosalind; Kote-Jarai, Zsofia; Muir, Kenneth; Schleutker, Johanna; Pashayan, Nora; Batra, Jyotsna; Grönberg, Henrik; Neal, David; Donovan, Jenny; Hamdy, Freddie; Martin, Richard; Nielsen, Sune; Nordestgaard, Børge; Wiklund, Fredrik; Tangen, Catherine; Giles, Graham; Wolk, Alicja; Albanes, Demetrius; Travis, Ruth; Blot, William; Zheng, Wei; Sanderson, Maureen; Stanford, Janet; Mucci, Lorelei; West, Catharine; Kibel, Adam; Cussenot, Olivier; Berndt, Sonja; Koutros, Stella; Sørensen, Karina Dalsgaard; Cybulski, Cezary; Grindedal, Eli Marie; Menegaux, Florence; Khaw, Kay-Tee; Park, Jong; Ingles, Sue; Maier, Christiane; Hamilton, Robert; Thibodeau, Stephen; Rosenstein, Barry; Lu, Yong-Jie; Watya, Stephen; Vega, Ana; Kogevinas, Manolis; Penney, Kathryn; Huff, Chad; Teixeira, Manuel; Multigner, Luc; Leach, Robin; Cannon-Albright, Lisa; Brenner, Hermann; John, Esther; Kaneva, Radka; Logothetis, Christopher; Neuhausen, Susan; Ruyck, Kim De; Pandha, Hardev; Razack, Azad; Newcomb, Lisa; Fowke, Jay; Gamulin, Marija; Usmani, Nawaid; Claessens, Frank; Gago-Dominguez, Manuela; Townsend, Paul; Bush, William; Srivastava, Shiv; Roobol, Monique; Parent, Marie-Élise; Hu, Jennifer; Mills, Ian; Andreassen, Ole; Dale, Anders; Seibert, Tyler; UKGPCS collaborators; APCB (Australian Prostate Cancer BioResource); NC-LA PCaP Investigators; The IMPACT Study Steering Committee and Collaborators; Canary PASS Investigators; The Profile Study Steering Committee; The PRACTICAL Consortium |
| Source: |
medRxiv |
| Publication Year: |
2019 |
| Subject Terms: |
APCB (Australian Prostate Cancer BioResource); Canary PASS Investigators; NC-LA PCaP Investigators; The IMPACT Study Steering Committee and Collaborators; The PRACTICAL Consortium; The Profile Study Steering Committee; UKGPCS collaborators |
| Description: |
Objectives A polygenic hazard score (PHS 1 )—weighted sum of 54 single-nucleotide polymorphism genotypes—was previously associated with age at prostate cancer (PCa) diagnosis and improved PCa screening accuracy in Europeans. Performance in more diverse populations is unknown. We evaluated PHS association with PCa in multi-ethnic populations. Design PHS 1 was adapted for compatibility with genotype data from the OncoArray project (PHS 2 ) and tested for association with age at PCa diagnosis, at aggressive PCa diagnosis, and at PCa death. Setting Multiple international institutions. Participants Men with available OncoArray data from the PRACTICAL consortium who were not included in PHS 1 development/validation. Main Outcomes and Measures PHS 2 was tested via Cox proportional hazards models for age at PCa diagnosis, age at aggressive PCa diagnosis (any of: Gleason score ≥7, stage T3-T4, PSA≥10 ng/mL, nodal/distant metastasis), and age at PCa-specific death. Results 80,491 men of various self-reported race/ethnicities were included (30,575 controls, 49,916 PCa cases; genetic ancestry groups: 71,856 European, 6,253 African, 2,382 Asian). Median age at last follow-up was 70 years (IQR 63-76); 3,983 PCa deaths, 5,806 other deaths, 70,702 still alive. PHS 2 had 46 polymorphisms: 24 directly genotyped and 22 acceptable proxies (r 2 ≥0.94). PHS 2 was associated with age at PCa diagnosis in the multi-ethnic dataset (z=54, p |
| Document Type: |
report |
| File Description: |
application/pdf |
| Language: |
unknown |
| Relation: |
https://lirias.kuleuven.be/handle/123456789/684914; https://doi.org/10.1101/19012237 |
| DOI: |
10.1101/19012237 |
| Availability: |
https://lirias.kuleuven.be/handle/123456789/684914; https://lirias.kuleuven.be/retrieve/43843d47-9dfc-477e-b522-aee9cb001a2f; https://doi.org/10.1101/19012237 |
| Rights: |
info:eu-repo/semantics/openAccess ; public ; All rights reserved |
| Accession Number: |
edsbas.CB5EB62D |
| Database: |
BASE |