Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA.
Center for Multimodal Imaging and Genetics, University of California San Diego, La Jolla, CA, USA.
Nat Commun. 2021 Feb 23;12(1):1236. doi: 10.1038/s41467-021-21287-0.
Genetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS) is associated with age at prostate cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS (PHS, adapted for OncoArray) in a multi-ethnic dataset of 80,491 men (49,916 cases, 30,575 controls). PHS 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). Comparing the 80/20 PHS 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. PHS risk-stratifies men for any, aggressive, and fatal prostate cancer in a multi-ethnic dataset.
癌症的遗传模型几乎仅使用欧洲数据进行评估,这可能会加剧健康差异。多基因危险评分(PHS)与前列腺癌诊断时的年龄相关,并提高了欧洲人的筛查准确性。在这里,我们评估了多基因危险评分(PHS,适用于 OncoArray)在 80491 名男性(49916 例病例,30575 例对照)的多民族数据集的表现。PHS 与任何类型和侵袭性前列腺癌(Gleason 评分≥7、T3-T4 期、PSA≥10ng/ml 或淋巴结/远处转移)以及前列腺癌特异性死亡的诊断年龄相关。在欧洲(n=71856)、亚洲(n=2382)和非洲(n=6253)遗传血统内,与癌症的关联具有统计学意义(p<10)。比较 80/20 PHS 百分位数,前列腺癌、侵袭性癌症和前列腺癌特异性死亡的风险比分别为 5.32、5.88 和 5.68。在欧洲、亚洲和非洲血统中,前列腺癌的风险比分别为:5.54、4.49 和 2.54。PHS 在多民族数据集中对所有、侵袭性和致命性前列腺癌进行了男性风险分层。