Henrikson Nora B, Scrol Aaron, Zepp Jamilyn M, Anderson Melissa L, Blasi Paula R, Ewing John J, Grafton Jane, Ralston James D, Fullerton Stephanie M, Leppig Kathleen A
Kaiser Permanente Washington Health Research Institute, Seattle, Washington, USA.
Department of Translational and Applied Genomics, Kaiser Permanente Northwest Center for Health Research, Portland, Oregon, USA.
Public Health Genomics. 2025;28(1):150-162. doi: 10.1159/000545404. Epub 2025 Apr 3.
At-risk relatives of probands with genetic variants associated with hereditary cancer risk should receive cascade genetic testing. In the USA, probands are expected to notify their own at-risk relatives, but many relatives never learn of their risk, representing missed opportunity to reduce morbidity and mortality associated with hereditary cancers. Direct contact of relatives could reach relatives not contacted by the proband. We conducted a single-arm, prospective pilot evaluation of a direct contact intervention based on patient and family preferences. Here, we report the study's quantitative results, measured by proband and relative participation in the intervention follow-up survey.
We recruited adults receiving genetic counseling for inherited cancer risk at one US integrated health system. A genetic counselor offered to contact at-risk relatives. We surveyed probands and relatives at study enrollment and 6-8 weeks and evaluated administrative data to assess the program's outreach to probands and relatives, its acceptability, and its limited efficacy.
We approached 148 probands before their genetic counseling appointment. Fifty-five (37%) consented to study participation. Of these, 31 completed genetic testing, 29 of whom provided consent to contact 101 relatives. Forty-four percent (n = 45) of relatives consented to be contacted by the study genetic counselor. Acceptability was high for both groups and no harms were reported. All relatives reached (n = 43) received their proband's test results, including 6 pathogenic/likely pathogenic findings.
A direct contact program was acceptable, reached at-risk relatives, and communicated proband test results. Direct contact with early consent of relatives holds promise for future research.
携带与遗传性癌症风险相关基因变异的先证者的高危亲属应接受级联基因检测。在美国，先证者有望通知自己的高危亲属，但许多亲属从未得知自己的风险，这意味着失去了降低与遗传性癌症相关的发病率和死亡率的机会。直接联系亲属可以联系到先证者未联系的亲属。我们基于患者和家庭偏好对直接接触干预措施进行了单臂前瞻性试点评估。在此，我们报告该研究的定量结果，以先证者和亲属参与干预后续调查的情况来衡量。
我们在美国一个综合医疗系统中招募了因遗传性癌症风险接受遗传咨询的成年人。一名遗传咨询师提出联系高危亲属。我们在研究入组时以及6至8周时对先证者和亲属进行了调查，并评估了行政数据，以评估该项目对先证者和亲属的宣传推广情况、可接受性及其有限的效果。
在148名先证者进行遗传咨询预约前与他们进行了接触。其中55名（37%）同意参与研究。在这些人中，31人完成了基因检测，其中29人同意联系101名亲属。44%（n = 45）的亲属同意由研究遗传咨询师联系。两组的可接受性都很高，且未报告有不良影响。所有被联系到的亲属（n = 43）都收到了先证者的检测结果，包括6个致病/可能致病的结果。
直接接触项目是可接受的，联系到了高危亲属，并传达了先证者的检测结果。在亲属早期同意的情况下进行直接接触有望用于未来的研究。
