Abstract：
Advances in our understanding of the genetic landscape of hereditary breast and ovarian cancer (HBOC) have led to the clinical adoption of multi-gene panel testing. Panel testing introduces new sources of genetic uncertainty secondary to the inclusion of moderate- and low-penetrance genes, as well as the increased likelihood of identifying a variant of uncertain significance (VUS). This cross-sectional study explored the post-test psychological functioning of women who underwent multi-gene panel testing for HBOC susceptibility genes. Two hundred and ninety-five women who underwent panel testing within the previous 2 years completed a study questionnaire to measure levels of cancer-related and genetic testing-related distress using the Impact of Events Scale (IES) and the Multidimensional Impact of Cancer Risk Assessment (MICRA), respectively. Multiple regression analyses were conducted to evaluate the relationship between genetic test results and levels of psychological distress captured by the IES and MICRA. In this cohort, a pathogenic variant (PV) was identified in 41 (14%) of participants, and 77 (26%) participants were found to have a VUS. In the multi-variate model, higher mean levels of genetic testing-related distress were observed in individuals with a PV (p < 0.001) or a VUS (p = 0.007) compared to those with a negative result. Furthermore, participants with a PV in a moderate-penetrance gene were found to have higher levels of genetic testing-related distress compared to those with a PV in a high-risk gene (p = 0.03). Overall, participants were highly satisfied with their genetic testing experience, with 92% of individuals reporting they would recommend testing to others. Our findings highlight differences in psychological outcomes based on both variant pathogenicity and gene penetrance, which contribute to our understanding of the impact of panel testing and sources of both cancer-related and genetic testing-related distress secondary to testing.
摘要：
我们对遗传性乳腺癌和卵巢癌（HBOC）遗传景观的理解的进步导致了多基因小组测试的临床采用。面板测试引入了新的遗传不确定性来源，其次是包含中等和低外显率基因，以及识别不确定显著性变异(VUS)的可能性增加。这项横断面研究探讨了接受HBOC易感基因多基因小组测试的女性的测试后心理功能。在过去两年内接受小组测试的二百九十五名妇女完成了一份研究问卷，以使用事件影响量表（IES）和癌症风险评估的多维影响（MICRA）来测量癌症相关和基因检测相关的困扰水平。分别。进行了多元回归分析，以评估IES和MICRA捕获的遗传测试结果与心理困扰水平之间的关系。在这个队列中，在41名(14%)参与者中发现了致病性变异(PV)，77名(26%)参与者被发现患有VUS。在多变量模型中，与阴性结果相比,在PV(p<0.001)或VUS(p=0.007)的个体中观察到更高的基因检测相关窘迫的平均水平.此外，与具有高风险基因的PV的参与者相比,具有中等外显率基因的PV的参与者具有更高水平的基因检测相关的痛苦(p=0.03).总的来说,参与者对他们的基因检测经验非常满意，92%的人报告他们会向其他人推荐测试。我们的发现强调了基于变异致病性和基因外显率的心理结果的差异，这有助于我们了解小组检测的影响以及癌症相关和基因检测相关的继发于检测的困扰的来源。
