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.
Highlights
Prostate cancer is the second most common cancer diagnosed in men worldwide, causing substantial morbidity and mortality[1]
PHS2 was associated with age at prostate cancer diagnosis in all three OncoArray-defined genetic ancestry groups (Table 1)
Hazard ratios (HRs) for aggressive prostate cancer comparing the 80th and 20th percentiles of genetic risk when participants are stratified by their self-reported race/ethnicity are shown in the Supplementary Information. These results confirm the previously reported association of polygenic hazard score (PHS) with age at prostate cancer diagnosis in Europeans and show that this finding generalizes to a multi-ethnic dataset, including men of European, Asian, and African ancestry
Summary
Prostate cancer is the second most common cancer diagnosed in men worldwide, causing substantial morbidity and mortality[1]. While genetic risk models might be important clinical tools for prognostication and risk stratification, using them may worsen health disparities[20,21,22,23,24] because most models are constructed using European data and may underrepresent genetic variants important in persons of non-European ancestry[20,21,22,23,24] This is concerning in prostate cancer, as race/ethnicity is an important prostate cancer risk factor; diagnostic, treatment, and outcomes disparities continue to exist between different races/ethnicities[25,26]. We assessed PHS performance in a multi-ethnic dataset that includes individuals of European, African, and Asian genetic ancestry This dataset includes long-term follow-up information, affording an opportunity to evaluate PHS for association with fatal prostate cancer
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