Ahsan Muhammad Danyal, Levi Sarah R, Webster Emily M, Bergeron Hannah, Lin Jenny, Narayan Priyanka, Nelson Becky Baltich, Li Xuan, Fowlkes Rana K, Brewer Jesse T, Thomas Charlene, Christos Paul J, Chapman-Davis Eloise, Cantillo Evelyn, Holcomb Kevin, Sharaf Ravi N, Frey Melissa K
Weill Cornell Medicine, New York, NY, USA.
PEC Innov. 2023 Feb 17;2:100138. doi: 10.1016/j.pecinn.2023.100138. eCollection 2023 Dec.
To evaluate rates of familial disclosure of hereditary cancer syndrome information.
A systematic review and meta-analysis was conducted in accordance with PRISMA guidelines (PROSPERO no.: CRD42020134276). Key electronic databases were searched to identify studies evaluating hereditary cancer syndrome cascade relative disclosure. Eligible studies were subjected to meta-analysis.
Thirty-four studies met inclusion criteria. Among 11,711 included relatives, 70% (95% CI 60 - 78%) were informed of their risk of carrying a cancer-associated pathogenic variant; of 2,875 relatives informed of their risk who were evaluated for uptake of cascade testing, 43% (95% CI 27 - 61%) completed testing. Rates of disclosure were higher among female vs male relatives (79% [95% CI 73% - 84%] vs 67% [95% CI 57% - 75%]) and first-degree vs second-degree relatives (83% [95% CI 77% - 88%] vs 58% [95% CI 45 - 69%]).
Nearly one-third of at-risk relatives remain uninformed of their risk of carrying a cancer-associated pathogenic variant. Even among those informed, fewer than half subsequently complete genetic testing, representing a critical missed opportunity for precision cancer prevention.
Five studies evaluating interventions to improve disclosure rates were generally ineffective. Urgent work is needed to elucidate barriers to relative disclosure by probands to develop targeted interventions that can optimize proband-mediated cascade genetic testing rates.
评估遗传性癌症综合征信息的家族披露率。
根据PRISMA指南（PROSPERO编号：CRD42020134276）进行了系统评价和荟萃分析。检索了主要电子数据库，以确定评估遗传性癌症综合征级联相关披露情况的研究。对符合条件的研究进行荟萃分析。
34项研究符合纳入标准。在11711名纳入的亲属中，70%（95%CI 60 - 78%）被告知其携带与癌症相关的致病变异的风险；在2875名被告知风险并接受级联检测评估的亲属中，43%（95%CI 27 - 61%）完成了检测。女性亲属的披露率高于男性亲属（79%[95%CI 73% - 84%]对67%[95%CI 57% - 75%]），一级亲属高于二级亲属（83%[95%CI 77% - 88%]对58%[95%CI 45 - 69%]）。
近三分之一的高危亲属仍未被告知其携带与癌症相关的致病变异的风险。即使在那些被告知的人中，随后完成基因检测的也不到一半，这代表着精准癌症预防中一个关键的错失机会。
五项评估改善披露率干预措施的研究总体上无效。迫切需要开展工作，以阐明先证者向亲属披露信息的障碍，从而制定有针对性的干预措施，优化先证者介导的级联基因检测率。
