Battistuzzi Linda
U.O. Oncologia Medica 2, IRCCS Ospedale Policlinico San Martino, Genova, Italy.
Tumori. 2024 Nov 13:3008916241297782. doi: 10.1177/03008916241297782.
Progress in the discovery and understanding of cancer susceptibility genes and ever-cheaper genomic technologies are generating precious opportunities to optimize the identification of individuals with a hereditary cancer predisposition.Any such effort will have a more significant impact if it prioritizes those most at risk of developing cancer. This premise is central to cascade genetic testing, in which healthcare professionals encourage cancer patients carrying a predisposing gene variant to discuss the implications of their test results with their at-risk relatives so that, ideally, all the at-risk individuals in that family have the option to seek genetic counseling and testing in turn. Among the relatives found to have the gene variant, those who have developed cancer can then access targeted treatment and follow-up, those who are asymptomatic can benefit from enhanced preventive measures, while those who test negative can avoid unnecessary, costly, and time-consuming screening.Despite its life-saving potential, cascade genetic testing in hereditary cancer syndromes is often reported to have disappointing uptake rates, particularly among historically disadvantaged and underrepresented communities, for reasons that include barriers in intrafamilial genetic risk communication and low health and genetic literacy.This paper will discuss the challenges of cascade genetic testing in hereditary cancer syndromes, addressing some of the ethical questions arising from its current model, from strategies aimed at improving its uptake, as well as from alternative approaches to identifying asymptomatic individuals who may carry a cancer- associated pathogenic variant.
在癌症易感性基因的发现与理解方面取得的进展以及日益廉价的基因组技术，正创造出宝贵机遇，以优化对具有遗传性癌症易感性个体的识别。如果将那些患癌风险最高的人群作为优先考虑对象，任何此类努力都将产生更大影响。这一前提对于级联基因检测至关重要，在级联基因检测中，医疗保健专业人员鼓励携带致病基因变异的癌症患者与其有风险的亲属讨论检测结果的影响，以便理想情况下，该家族中所有有风险的个体都能依次选择寻求遗传咨询和检测。在被发现携带该基因变异的亲属中，那些已患癌症的人随后可获得靶向治疗和随访，那些无症状的人可受益于强化预防措施，而检测结果为阴性的人可避免不必要的、昂贵且耗时的筛查。尽管级联基因检测在遗传性癌症综合征中具有挽救生命的潜力，但据报道其接受率往往令人失望，尤其是在历史上处于不利地位和代表性不足的社区，原因包括家族内遗传风险沟通的障碍以及健康和基因素养较低。本文将讨论遗传性癌症综合征中级联基因检测的挑战，探讨其当前模式引发的一些伦理问题、旨在提高其接受率的策略，以及识别可能携带与癌症相关致病变异的无症状个体的替代方法。
