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波兰男性中该基因种系变异的临床意义及其与前列腺癌风险的关联:一项病例对照研究。

Clinical Significance of Germline Variants in the Gene and Their Association With Prostate Cancer Risk in Polish Men: A Case-Control Study.

作者信息

Heise Marta, Jarzemski Piotr, Kuk Julia

机构信息

Department of Clinical Genetics, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland.

Department of Urology, Jan Biziel University Hospital in Bydgoszcz, Bydgoszcz, Poland.

出版信息

Cancer Control. 2025 Jan-Dec;32:10732748251327720. doi: 10.1177/10732748251327720. Epub 2025 Apr 22.

Abstract

ObjectivesCurrently, prostate cancer (PC) is the most common medical problem endangering men's health and life worldwide. We tested the association of detected germline variants in with PC risk and estimated their impact on the clinical course of the disease, including overall survival time, in Polish men with localized PC that qualified for radical prostatectomy (RP).Materials and MethodsDNA of 97 PC patients from various age groups and with different disease stages was analyzed. Control DNA samples consisted of 100 male volunteers without PC that were age-matched to the study group. Next Generation Sequencing (NGS) and Sanger sequencing were used for variant detection.ResultsFive rare variants of the gene were detected in single PC patients. There were four substitutions (c.8010G>C, c.682-32A>G, c.9257-75G>C, c.516+17G>C) and one deletion (c.6393_6396del). Among the detected variants, one was pathogenic, one was a variant of uncertain significance (VUS), and three were likely benign. The c.8010G>C was a new variant. In the carrier of the c.6393_6396del pathogenic variant, PC was diagnosed at the T3 stage and the patient survived 48 months after PC confirmation (the date of biopsy).ConclusionsThe c.6393_6396del pathogenic variant demonstrates an association with clinical features of the disease (GS and TNM) and shorter survival of patients with localized prostate cancer that qualified for RP. Additionally, our findings suggest that multi-organ cancer aggregation in a family, including prostate cancer aggregation in close relatives, and young age at cancer onset should be taken into consideration by clinicians as an indication to refer patients to molecular testing.

摘要

目的

目前,前列腺癌(PC)是全球范围内危害男性健康和生命的最常见医学问题。我们检测了[基因名称未给出]中检测到的种系变异与PC风险的关联,并估计了它们对符合根治性前列腺切除术(RP)的波兰局限性PC男性患者疾病临床进程的影响,包括总生存时间。

材料和方法

分析了97例不同年龄组和不同疾病阶段的PC患者的DNA。对照DNA样本由100名无PC的男性志愿者组成,其年龄与研究组匹配。采用下一代测序(NGS)和桑格测序进行变异检测。

结果

在单个PC患者中检测到[基因名称未给出]的五个罕见变异。有四个替换(c.8010G>C、c.682-32A>G、c.9257-75G>C、c.516+17G>C)和一个缺失(c.6393_6396del)。在检测到的变异中,一个是致病性的,一个是意义未明的变异(VUS),三个可能是良性的。c.8010G>C是一个新变异。在携带c.6393_6396del致病性变异的患者中,PC在T3期被诊断,患者在PC确诊(活检日期)后存活了48个月。

结论

c.6393_6396del致病性变异与疾病的临床特征(GS和TNM)以及符合RP的局限性前列腺癌患者的较短生存期相关。此外,我们的研究结果表明,临床医生应将家族性多器官癌症聚集,包括近亲中的前列腺癌聚集,以及癌症发病年龄较轻视为将患者转诊进行分子检测的指征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d48/12035019/af292c9956d0/10.1177_10732748251327720-fig1.jpg

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