Exeter Centre of Excellence for Diabetes Research (EXCEED), University of Exeter Medical School, St Luke's Campus, University of Exeter, Heavitree Road, Exeter, Devon, EX1 2LU, UK.
DISCOVERY Group, University of Exeter Medical School, St Luke's Campus, University of Exeter, Heavitree Road, Exeter, Devon, EX1 2LU, UK.
Br J Cancer. 2022 Nov;127(8):1534-1539. doi: 10.1038/s41416-022-01918-z. Epub 2022 Aug 18.
Prostate cancer is highly heritable, with >250 common variants associated in genome-wide association studies. It commonly presents with non-specific lower urinary tract symptoms that are frequently associated with benign conditions.
Cohort study using UK Biobank data linked to primary care records. Participants were men with a record showing a general practice consultation for a lower urinary tract symptom. The outcome measure was prostate cancer diagnosis within 2 years of consultation. The predictor was a genetic risk score of 269 genetic variants for prostate cancer.
A genetic risk score (GRS) is associated with prostate cancer in symptomatic men (OR per SD increase = 2.12 [1.86-2.41] P = 3.5e-30). An integrated risk model including age and GRS applied to symptomatic men predicted prostate cancer (AUC 0.768 [0.739-0.796]). Prostate cancer incidence was 8.1% (6.7-9.7) in the highest risk quintile. In the lowest quintile, prostate cancer incidence was <1%.
This study is the first to apply GRS in primary care to improve the triage of symptomatic patients. Men with the lowest genetic risk of developing prostate cancer could safely avoid invasive investigation, whilst those identified with the greatest risk could be fast-tracked for further investigation. These results show that a GRS has potential application to improve the diagnostic pathway of symptomatic patients in primary care.
前列腺癌具有高度遗传性，全基因组关联研究发现了超过 250 个常见变异。它通常表现为非特异性下尿路症状，常与良性疾病有关。
使用英国生物银行（UK Biobank）数据进行队列研究，并与初级保健记录相关联。参与者为有下尿路症状的一般实践咨询记录的男性。结局指标为咨询后 2 年内前列腺癌的诊断。预测指标是 269 个前列腺癌遗传风险变异的遗传风险评分。
遗传风险评分（GRS）与有症状男性的前列腺癌相关（每增加一个标准差的 OR=2.12[1.86-2.41]，P=3.5e-30）。一个包含年龄和 GRS 的综合风险模型应用于有症状的男性，可以预测前列腺癌（AUC 为 0.768[0.739-0.796]）。在最高风险五分位数中，前列腺癌的发病率为 8.1%（6.7-9.7）。在最低五分位数中，前列腺癌的发病率<1%。
这项研究是首次将 GRS 应用于初级保健，以改善有症状患者的分诊。患有前列腺癌最低遗传风险的男性可以安全地避免侵入性检查，而那些遗传风险最高的男性可以快速进行进一步检查。这些结果表明，GRS 有可能应用于改善初级保健中症状患者的诊断途径。
