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%至10%。基因突变的发现可能对药物治疗、个性化预防策略以及级联检测产生深远影响。根据美国国家综合癌症网络（NCCN）和意大利医学肿瘤学协会（AIOM）的指南，未受影响的家庭成员仅应在受影响者无法进行检测的情况下接受测试。本文探讨了即使缺乏在世的受影响亲属，是否仍可向高风险遗传性癌症家族提供种系基因检测。我们对2017年至2023年间接受检测的103名健康受试者进行了回顾性研究。所有受试者均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。所有受试者均通过包含27个癌症相关基因的新一代测序（NGS）多基因组合进行检测。在研究人群中，发现5例（约5%）致病性/可能致病性变异（PVs/LPVs），而40例（42%）存在意义未明变异（VUS）。本研究强调了对于具有显著遗传性恶性肿瘤家族史的个体进行基因检测的重要性。这一方法将使检测结果呈阳性的女性能够根据其个人突变状态获得量身定制的治疗和预防策略。
肿瘤(癌症)患者之家