Tsoulos Nikolaos, Papadopoulou Eirini, Agiannitopoulos Konstantinos, Grigoriadis Dimitrios, Tsaousis Georgios N, Bouzarelou Dimitra, Gogas Helen, Troupis Theodore, Venizelos Vassileios, Fountzilas Elena, Theochari Maria, Ziogas Dimitrios C, Giassas Stylianos, Koumarianou Anna, Christopoulou Athina, Busby George, Nasioulas George, Markopoulos Christos
Genekor Medical S.A., 15344 Athens, Greece.
First Department of Internal Medicine, Laikon General Hospital, School of Medicine, National Kapodistrian University of Athens, 11527 Athens, Greece.
Diagnostics (Basel). 2024 Aug 21;14(16):1826. doi: 10.3390/diagnostics14161826.
Breast cancer (BC) is the most prominent tumor type among women, accounting for 32% of newly diagnosed cancer cases. BC risk factors include inherited germline pathogenic gene variants and family history of disease. However, the etiology of the disease remains occult in most cases. Therefore, in the absence of high-risk factors, a polygenic basis has been suggested to contribute to susceptibility. This information is utilized to calculate the Polygenic Risk Score (PRS) which is indicative of BC risk. This study aimed to evaluate retrospectively the clinical usefulness of PRS integration in BC risk calculation, utilizing a group of patients who have already been diagnosed with BC. The study comprised 105 breast cancer patients with hereditary genetic analysis results obtained by NGS. The selection included all testing results: high-risk gene-positive, intermediate/low-risk gene-positive, and negative. PRS results were obtained from an external laboratory (Allelica). PRS-based BC risk was computed both with and without considering additional risk factors, including gene status and family history. A significantly different PRS percentile distribution consistent with higher BC risk was observed in our cohort compared to the general population. Higher PRS-based BC risks were detected in younger patients and in those with FH of cancers. Among patients with a pathogenic germline variant detected, reduced PRS values were observed, while the BC risk was mainly determined by a monogenic etiology. Upon comprehensive analysis encompassing FH, gene status, and PRS, it was determined that 41.90% (44/105) of the patients demonstrated an elevated susceptibility for BC. Moreover, 63.63% of the patients with FH of BC and without an inherited pathogenic genetic variant detected showed increased BC risk by incorporating the PRS result. Our results indicate a major utility of PRS calculation in women with FH in the absence of a monogenic etiology detected by NGS. By combining high-risk strategies, such as inherited disease analysis, with low-risk screening strategies, such as FH and PRS, breast cancer risk stratification can be improved. This would facilitate the development of more effective preventive measures and optimize the allocation of healthcare resources.
乳腺癌（BC）是女性中最常见的肿瘤类型，占新诊断癌症病例的32%。BC的风险因素包括遗传性种系致病基因变异和家族病史。然而，在大多数情况下，该疾病的病因仍不明确。因此，在没有高危因素的情况下，有人提出多基因基础可能导致易感性。这些信息被用于计算多基因风险评分（PRS），它可指示BC风险。本研究旨在利用一组已被诊断为BC的患者，回顾性评估PRS整合在BC风险计算中的临床实用性。该研究包括105例通过二代测序（NGS）获得遗传性基因分析结果的乳腺癌患者。入选患者涵盖所有检测结果：高危基因阳性、中/低危基因阳性和阴性。PRS结果来自外部实验室（Allelica）。在考虑和不考虑包括基因状态和家族病史等其他风险因素的情况下，均计算基于PRS的BC风险。与一般人群相比，我们的队列中观察到与更高BC风险一致的显著不同的PRS百分位数分布。在年轻患者和有癌症家族史的患者中检测到基于PRS的更高BC风险。在检测到种系致病变异的患者中，观察到PRS值降低，而BC风险主要由单基因病因决定。在综合分析家族病史、基因状态和PRS后，确定41.90%（44/105）的患者表现出对BC的易感性增加。此外，在未检测到遗传性致病基因变异但有BC家族史的患者中，通过纳入PRS结果，63.63%的患者显示BC风险增加。我们的结果表明，在未通过NGS检测到单基因病因的有家族病史的女性中，PRS计算具有重要作用。通过将诸如遗传性疾病分析等高风险策略与诸如家族病史和PRS等低风险筛查策略相结合，可以改善乳腺癌风险分层。这将有助于制定更有效的预防措施，并优化医疗资源的分配。
