PDF(Pubmed)
Abstract：
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.
摘要：
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会对药物治疗产生深远的影响，个性化预防策略，和级联测试。根据国家综合癌症网络（NCCN）和意大利医学肿瘤协会（AIOM）指南，只有当受影响的家庭成员不可用时，才应测试未受影响的家庭成员。这篇文章探讨了是否可以为遗传性癌症的高风险家庭提供种系基因检测，即使一个活着的受影响的亲属失踪。对2017年至2023年接受测试的103名健康受试者进行了回顾性研究。我们招募了所有至少有两个一级或二级亲属受乳房影响的受试者，卵巢,胰腺,胃,前列腺,或结直肠癌。通过27个癌症相关基因的下一代测序(NGS)多基因组测试所有受试者。在研究人群中，5（约5％）致病性/可能致病性变异（PVs/LPVs）被发现，而40人(42%)有不确定显著性变异(VUS)。这项研究强调了遗传检测对具有强烈遗传性恶性肿瘤家族史的个体的重要性。这种方法将允许检测呈阳性的女性根据其个人突变状况接受量身定制的治疗和预防策略。
