Polygenic hazard score is associated with prostate cancer in multi-ethnic populations
Huynh-Le M., Fan CC., Karunamuni R., Thompson WK., Martinez ME., Eeles RA., Kote-Jarai Z., Muir K., Schleutker J., Pashayan N., Batra J., Grönberg H., Neal DE., Donovan JL., Hamdy FC., Martin RM., Nielsen SF., Nordestgaard BG., Wiklund F., Tangen CM., Giles GG., Wolk A., Albanes D., Travis RC., Blot WJ., Zheng W., Sanderson M., Stanford JL., Mucci LA., West CML., Kibel AS., Cussenot O., Berndt SI., Koutros S., Sørensen KD., Cybulski C., Grindedal EM., Menegaux F., Khaw K., Park JY., Ingles SA., Maier C., Hamilton RJ., Thibodeau SN., Rosenstein BS., Lu Y., Watya S., Vega A., Kogevinas M., Penney KL., Huff C., Teixeira MR., Multigner L., Leach RJ., Cannon-Albright L., Brenner H., John EM., Kaneva R., Logothetis CJ., Neuhausen SL., De Ruyck K., Pandha H., Razack A., Newcomb LF., Fowke JH., Gamulin M., Usmani N., Claessens F., Gago-Dominguez M., Townsend PA., Bush WS., Roobol MJ., Parent M., Hu JJ., Mills IG., Andreassen OA., Dale AM., Seibert TM., UKGPCS collaborators None., APCB (Australian Prostate Cancer BioResource) None., NC-LA PCaP Investigators None., The IMPACT Study Steering Committee and Collaborators None., Canary PASS Investigators None., The Profile Study Steering Committee None., The PRACTICAL Consortium None.
Genetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS1) is associated with age at prostate cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS2 (PHS1, adapted for OncoArray) in a multi-ethnic dataset of 80,491 men (49,916 cases, 30,575 controls). PHS2 is associated with age at diagnosis of any and aggressive (Gleason score ≥ 7, stage T3-T4, PSA ≥ 10 ng/mL, or nodal/distant metastasis) cancer and prostate-cancer-specific death. Associations with cancer are significant within European (n = 71,856), Asian (n = 2,382), and African (n = 6,253) genetic ancestries (p < 10−180). Comparing the 80th/20th PHS2 percentiles, hazard ratios for prostate cancer, aggressive cancer, and prostate-cancer-specific death are 5.32, 5.88, and 5.68, respectively. Within European, Asian, and African ancestries, hazard ratios for prostate cancer are: 5.54, 4.49, and 2.54, respectively. PHS2 risk-stratifies men for any, aggressive, and fatal prostate cancer in a multi-ethnic dataset.