Kiyozumi Yoshimi, Nishimura Seiichiro, Kado Nobuhiro, Higashigawa Satomi, Horiuchi Yasue, Ishihara Eiko, Harada Rina, Matsubayashi Hiroyuki
Division of Genetic Medicine Promotion, Shizuoka Cancer Center, Shizuoka, Japan.
Division of Breast Surgery, Shizuoka Cancer Center, Shizuoka, Japan.
J Genet Couns. 2025 Jun;34(3):e70055. doi: 10.1002/jgc4.70055.
In clinical management for hereditary cancer patients, risk assessment is needed not only for patients but also for their blood relatives. In people with Hereditary Breast and Ovarian Cancer syndrome (HBOC), benefits are demonstrated by identifying relatives with BRCA1 and BRCA2 pathogenic germline variants (PGV) and implementing clinical surveillance and risk-reduction surgeries for the at-risk organs. To date, the uptake of cascade testing has been reported to be insufficient, but only a limited number of studies have analyzed the barriers to cascade testing. The current study aimed to analyze the uptake of cascade testing in the relatives of Japanese HBOC probands and clarify the factors that promote cascade testing uptake. This retrospective study included 125 probands carrying BRCA1 or BRCA2 PGV and 425 of their first-degree relatives (FDRs). Individual clinicodemographic data were collected from medical records, and comparisons were made between those who did and did not undergo cascade testing. Ninety-two (21.6%) FDRs of HBOC probands underwent cascade testing. Approximately 70% of the relatives underwent testing within 6 months of the proband's genetic testing. Independent predictors of cascade testing of 425 FDRs were: being present at the proband's genetic counseling session [odds ratio (OR): 8.3, 95% CI 4.2-16.1], cost-free testing (OR: 2.4, 95% CI 1.4-4.2), being the child of a proband (OR: 1.9, 95% CI 1.1-3.2), and female sex (OR: 1.8, 95% CI 1.0-3.0). The cascade testing uptake rate of FDRs in this study was similar to or lower than other countries. cascade testing uptake can be improved in HBOC families by encouraging relatives (children, siblings, and parents) to attend genetic counseling with the proband. Further prospective studies are needed to pursue the reasons for accepting cascade testing, including an evaluation of intrafamily communication processes.
在遗传性癌症患者的临床管理中，不仅需要对患者进行风险评估，还需要对其血亲进行风险评估。在遗传性乳腺癌和卵巢癌综合征（HBOC）患者中，通过识别携带BRCA1和BRCA2致病种系变异（PGV）的亲属，并对高危器官实施临床监测和降低风险的手术，已证明有获益。迄今为止，据报道级联检测的接受率不足，但仅有少数研究分析了级联检测的障碍。本研究旨在分析日本HBOC先证者亲属的级联检测接受情况，并阐明促进级联检测接受的因素。这项回顾性研究纳入了125名携带BRCA1或BRCA2 PGV的先证者及其425名一级亲属（FDR）。从医疗记录中收集个体临床人口统计学数据，并对接受和未接受级联检测的对象进行比较。HBOC先证者的92名（21.6%）FDR接受了级联检测。大约70%的亲属在先证者基因检测后的6个月内接受了检测。425名FDR进行级联检测的独立预测因素为：在先证者的遗传咨询会议上到场[比值比（OR）：8.3，95%置信区间4.2 - 16.1]、免费检测（OR：2.4，95%置信区间1.4 - 4.2）、为先证者的子女（OR：1.9，95%置信区间1.1 - 3.2）以及女性（OR：1.8，95%置信区间1.0 - 3.0）。本研究中FDR的级联检测接受率与其他国家相似或更低。通过鼓励亲属（子女、兄弟姐妹和父母）与先证者一同参加遗传咨询，可提高HBOC家族中级联检测的接受率。需要进一步开展前瞻性研究以探究接受级联检测的原因，包括对家庭内部沟通流程的评估。
