Polygenic hazard score is associated with prostate cancer in multi-ethnic populations
Open Access
- 23 February 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 12 (1), 1-9
- https://doi.org/10.1038/s41467-021-21287-0
Abstract
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.Funding Information
- U.S. Department of Health & Human Services | NIH | National Institute of Biomedical Imaging and Bioengineering (K08EB026503)
This publication has 53 references indexed in Scilit:
- Screening for prostate cancerEmergencias, 2013
- Evaluating Genetic Risk for Prostate Cancer among Japanese and LatinosCancer Epidemiology, Biomarkers & Prevention, 2012
- Risk factors for the onset of prostatic cancer: age, location, and behavioral correlatesClinical Epidemiology, 2012
- Radiotherapy and Short-Term Androgen Deprivation for Localized Prostate CancerThe New England Journal of Medicine, 2011
- Characterizing Genetic Risk at Known Prostate Cancer Susceptibility Loci in African AmericansPLoS Genetics, 2011
- Impact of Age at Diagnosis on Prostate Cancer Treatment and SurvivalJournal of Clinical Oncology, 2011
- African Genetic Diversity: Implications for Human Demographic History, Modern Human Origins, and Complex Disease MappingAnnual Review of Genomics and Human Genetics, 2008
- Multiple Novel Prostate Cancer Predisposition Loci Confirmed by an International Study: The PRACTICAL ConsortiumCancer Epidemiology, Biomarkers & Prevention, 2008
- Plasma Natriuretic Peptide Levels and the Risk of Cardiovascular Events and DeathThe New England Journal of Medicine, 2004
- Bootstrap Methods for Standard Errors, Confidence Intervals, and Other Measures of Statistical AccuracyStatistical Science, 1986