前列腺特异性抗原 (PSA) 水平受到与前列腺癌风险无关的遗传变异的影响。较高 PSA 水平的遗传倾向是否会导致前列腺癌诊断检查的倾向尚不清楚。参与者是 3110 名非洲和欧洲血统的男性，年龄 45-70 岁，没有前列腺癌，基线 PSA < 4 ng/mL ，接受常规临床 PSA 筛查。该暴露是多基因评分 (PGS)，包含 111 个与 PSA 水平相关的单核苷酸多态性，但与前列腺癌无关。我们测试了 PGS 是否与以下因素相关：1) PSA 值 > 4 ng/mL，2) PSA 升高的国际疾病分类 (ICD) 代码，3) 与泌尿科医生会面，或 4) 前列腺活检。多变量 Cox 比例风险模型根据年龄和遗传主成分进行了调整。分析按年龄（45-59 岁和 60-70 岁）进行分层。协会估计值是根据 PGS 中的标准差变化得出的。平均年龄为 56.6 岁，2118 名参与者 (68%) 年龄为 45-59 岁。中位 (IQR) 基线 PSA 水平为 1.0 (0.6-1.7) ng/mL。在 45-59 岁的男性中，PGS 与 PSA > 4 相关（风险比 [HR] = 1.35 [95% CI, 1.17-1.57], p = 4.5 × 10-5），这是 PSA 升高的 ICD 代码（ HR = 1.30 [1.12-1.52]，p = 8.0 × 10-4），泌尿外科评估（HR = 1.34 [1.14-1.57]，p = 4.8 × 10-4），并进行前列腺活检（HR = 1.35 [ 1.11-1.64]，p = 0.002）。在 60-70 岁的男性中，关联效应较小且不显着。45-59 岁男性中 PSA 水平升高的倾向与 PSA 升高的临床评估相关。美国国立卫生研究院 (NIH)。版权所有 © 2023作者。由 Elsevier B.V. 出版。保留所有权利。

Prostate-specific antigen (PSA) levels are influenced by genetic variation unrelated to prostate cancer risk. Whether a genetic predisposition to a higher PSA level predisposes to a diagnostic work-up for prostate cancer is not known.Participants were 3110 men of African and European ancestries ages 45-70, without prostate cancer and with a baseline PSA < 4 ng/mL, undergoing routine clinical PSA screening. The exposure was a polygenic score (PGS) comprising 111 single nucleotide polymorphisms associated with PSA level, but not prostate cancer. We tested whether the PGS was associated with a: 1) PSA value > 4 ng/mL, 2) International Classification of Diseases (ICD) code for an elevated PSA, 3) encounter with a urologist, or 4) prostate biopsy. Multivariable Cox proportional hazards models were adjusted for age and genetic principal components. Analyses were stratified by age (45-59 years, and 60-70 years old). Association estimates are per standard deviation change in the PGS.The median age was 56.6 years, and 2118 (68%) participants were 45-59 years. The median (IQR) baseline PSA level was 1.0 (0.6-1.7) ng/mL. Among men ages 45-59, the PGS was associated with a PSA > 4 (hazard ratio [HR] = 1.35 [95% CI, 1.17-1.57], p = 4.5 × 10-5), an ICD code for elevated PSA (HR = 1.30 [1.12-1.52], p = 8.0 × 10-4), a urological evaluation (HR = 1.34 [1.14-1.57], p = 4.8 × 10-4), and undergoing a prostate biopsy (HR = 1.35 [1.11-1.64], p = 0.002). Among men ages 60-70, association effect sizes were smaller and not significant.A predisposition toward higher PSA levels was associated with clinical evaluations of an elevated PSA among men ages 45-59 years.National Institutes of Health (NIH).Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.