Pilenzi Lucrezia, Anaclerio Federico, Dell'Elice Anastasia, Minelli Maria, Giansante Roberta, Cicirelli Michela, Tinari Nicola, Grassadonia Antonino, Pantalone Andrea, Grossi Simona, Canale Nicole, Bruno Annalisa, Calabrese Giuseppe, Ballerini Patrizia, Stuppia Liborio, Antonucci Ivana
Center for Advanced Studies and Technology (CAST), "G. d'Annunzio" University of Chieti-Pescara, 66100 Chieti, Italy.
Department of Medical Genetics, "G. d'Annunzio" University of Chieti-Pescara, 66100 Chieti, Italy.
Cancers (Basel). 2024 Jun 25;16(13):2327. doi: 10.3390/cancers16132327.
Hereditary cancer syndromes caused by germline mutations account for 5-10% of all cancers. The finding of a genetic mutation could have far-reaching consequences for pharmaceutical therapy, personalized prevention strategies, and cascade testing. According to the National Comprehensive Cancer Network's (NCCN) and the Italian Association of Medical Oncology (AIOM) guidelines, unaffected family members should be tested only if the affected one is unavailable. This article explores whether germline genetic testing may be offered to high-risk families for hereditary cancer even if a living affected relative is missing. A retrospective study was carried out on 103 healthy subjects tested from 2017 to 2023. We enrolled all subjects with at least two first- or second-degree relatives affected by breast, ovarian, pancreatic, gastric, prostate, or colorectal cancer. All subjects were tested by Next Generation Sequencing (NGS) multi-gene panel of 27 cancer-associated genes. In the study population, 5 (about 5%) pathogenic/likely pathogenic variants (PVs/LPVs) were found, while 40 (42%) had a Variant of Uncertain Significance (VUS). This study highlights the importance of genetic testing for individuals with a strong family history of hereditary malignancies. This approach would allow women who tested positive to receive tailored treatment and prevention strategies based on their personal mutation status.
由种系突变引起的遗传性癌症综合征占所有癌症的5%-10%。基因突变的发现可能对药物治疗、个性化预防策略和级联检测产生深远影响。根据美国国立综合癌症网络（NCCN）和意大利医学肿瘤学协会（AIOM）的指南，只有在无法对患病亲属进行检测时，才应对未受影响的家庭成员进行检测。本文探讨了即使没有在世的患病亲属，是否也可为遗传性癌症的高危家庭提供种系基因检测。对2017年至2023年期间接受检测的103名健康受试者进行了一项回顾性研究。我们纳入了所有至少有两名一级或二级亲属患有乳腺癌、卵巢癌、胰腺癌、胃癌、前列腺癌或结直肠癌的受试者。所有受试者均通过对27个癌症相关基因的二代测序（NGS）多基因检测板进行检测。在研究人群中，发现了5个（约5%）致病/可能致病变异（PVs/LPVs），而40个（42%）有意义未明的变异（VUS）。这项研究强调了对有遗传性恶性肿瘤家族史的个体进行基因检测的重要性。这种方法将使检测呈阳性的女性能够根据其个人突变状态接受量身定制的治疗和预防策略。
