Program for Personalized Cancer Care, NorthShore University HealthSystem, Evanston, Illinois, USA.
Department of Surgery, NorthShore University HealthSystem, Evanston, Illinois, USA.
Prostate. 2021 Jul;81(10):703-709. doi: 10.1002/pros.24140. Epub 2021 May 6.
Prostate cancer (PCa) is characterized by its tendency to be multifocal. However, few studies have investigated the endogenous factors that explain the multifocal disease. The primary objective of the current study is to test whether inherited PCa risk is associated with multifocal tumors in PCa patients.
Subjects in this study were PCa patients of European ancestry undergoing active surveillance at Johns Hopkins Hospital (N = 805) and NorthShore University HealthSystem (N = 432). The inherited risk was measured by genetic risk score (GRS), an odds ratio-weighted and population-standardized polygenic risk score based on known risk-associated single nucleotide polymorphisms. PCa multifocality was indirectly measured by the number and laterality of positive tumor cores from a 12-core systematic biopsy.
In the combined cohort, 35.7% and 66.3% of patients had ≥2 tumor cores at the initial diagnostic biopsy and on at least one subsequent surveillance biopsy, respectively. For tumor laterality, 7.8% and 47.8% of patients had bilateral tumor cores at diagnostic and surveillance biopsies, respectively. We found, for the first time, that patients with higher numbers of positive cores at diagnostic and surveillance biopsies, respectively, had significantly higher mean GRS values; p = .01 and p = 5.94E-04. Additionally, patients with bilateral tumors at diagnostic and surveillance biopsies, respectively, had significantly higher mean GRS values than those with unilateral tumors; p = .04 and p = .01. In contrast, no association was found between GRS and maximum core length of tumor or tumor grade at diagnostic/surveillance biopsies (all p > .05). Finally, we observed a modest trend that patients with higher GRS quartiles had a higher risk for tumor upgrading on surveillance biopsies. The trend, however, was not statistically significant (p > .05).
The associations of GRS with two measurements of PCa multifocality (core numbers and laterality) provide novel and consistent evidence for the link between inherited PCa risk and multifocal tumors.
前列腺癌（PCa）的特征是多灶性。然而，很少有研究调查解释多灶性疾病的内在因素。本研究的主要目的是检验遗传的 PCa 风险是否与 PCa 患者的多灶性肿瘤有关。
本研究的研究对象为在约翰霍普金斯医院（n=805）和北岸大学健康系统（n=432）接受主动监测的欧洲裔 PCa 患者。遗传风险通过遗传风险评分（GRS）来衡量，这是一种基于已知风险相关单核苷酸多态性的比值比加权和人群标准化多基因风险评分。PCa 的多灶性通过 12 核系统活检中阳性肿瘤核心的数量和位置来间接测量。
在合并队列中，35.7%和 66.3%的患者在初始诊断活检和至少一次后续监测活检中分别有≥2 个肿瘤核心。就肿瘤位置而言，分别有 7.8%和 47.8%的患者在诊断和监测活检中有双侧肿瘤核心。我们首次发现，在诊断和监测活检中阳性核心数量较多的患者，其平均 GRS 值显著较高；p=0.01 和 p=5.94E-04。此外，在诊断和监测活检中分别有双侧肿瘤的患者，其平均 GRS 值明显高于单侧肿瘤患者；p=0.04 和 p=0.01。相比之下，在诊断/监测活检中，GRS 与肿瘤最大核心长度或肿瘤分级之间没有关联（所有 p>0.05）。最后，我们观察到一个适度的趋势，即 GRS 四分位值较高的患者在监测活检中肿瘤升级的风险较高。然而，这种趋势没有统计学意义（p>0.05）。
GRS 与 PCa 多灶性的两个测量值（核心数量和位置）之间的关联为遗传 PCa 风险与多灶性肿瘤之间的联系提供了新的一致证据。
