Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Department of Oncology, University Hospital Center Zagreb, University of Zagreb School of Medicine, 10000 Zagreb, Croatia.
Genes (Basel). 2022 Oct 27;13(11):1955. doi: 10.3390/genes13111955.
Germline pathogenic and likely pathogenic (P/LP) variants in have been associated with increased prostate cancer (PrCa) risk. Our objective was to analyze their occurrence in Croatian PrCa men and to evaluate the clinical characteristics of P/LP variant carriers. Therefore, we analyzed in 150 PrCa patients unselected for age of onset, family history of PrCa or clinical outcome, and the frequency of identified variants was compared to findings in 442 cancer-free men, of Croatian ancestry. We identified four PrCa cases harboring a P/LP variant in (4/150, 2.67%), which reached a statistical significance ( = 0.004) as compared to the control group. Patients with P/LP variants in developed PrCa almost 9 years earlier than individuals with wild-type alleles (8.9 years; = 0.0198) and had an increased risk for lymph node involvement ( = 0.0047). No association was found between status and further clinical characteristics, including the Gleason score, occurrence of aggressive PrCa, the tumor or metastasis stage. However, carriers of the most common P/LP CHEK2 variant, the c.1100delC, p.Thr367Met15*, had a significantly higher Gleason score ( = 0.034), risk for lymph node involvement ( = 0.0001), and risk for developing aggressive PrCa ( = 0.027). Thus, in a Croatian population, P/LP variant carriers were associated with increased risk for early onset prostate cancer, and carriers of the c.1100delC, p.Thr367Met15* had increased risk for aggressive PrCa.
胚系致病性和可能致病性 (P/LP) 变体与前列腺癌 (PrCa) 风险增加有关。我们的目的是分析它们在克罗地亚 PrCa 男性中的发生情况，并评估 P/LP 变体携带者的临床特征。因此，我们分析了 150 名未选择发病年龄、前列腺癌家族史或临床结果的 PrCa 患者中的 ，并将鉴定出的变体的频率与 442 名无癌的克罗地亚男性进行了比较。我们在 4 名患者中发现了 4 种 P/LP 变体 (4/150, 2.67%)，与对照组相比，这达到了统计学意义 ( = 0.004)。携带 变体的患者发生 PrCa 的时间比携带野生型等位基因的个体早近 9 年 (8.9 年； = 0.0198)，并且淋巴结受累的风险增加 ( = 0.0047)。在 状态与进一步的临床特征之间未发现关联，包括 Gleason 评分、侵袭性 PrCa 的发生、肿瘤或转移阶段。然而，最常见的 P/LP CHEK2 变体携带者，即 c.1100delC，p.Thr367Met15*，其 Gleason 评分明显更高 ( = 0.034)，淋巴结受累的风险更高 ( = 0.0001)，并且发生侵袭性 PrCa 的风险更高 ( = 0.027)。因此，在克罗地亚人群中，携带 变体的个体与前列腺癌发病年龄较早相关，而携带 c.1100delC，p.Thr367Met15*的个体发生侵袭性前列腺癌的风险增加。
