Lumish Heidi S, Steinfeld Hallie, Koval Carrie, Russo Donna, Levinson Elana, Wynn Julia, Duong James, Chung Wendy K
College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Division of Clinical Genetics, New York Presbyterian Hospital, New York, NY, USA.
J Genet Couns. 2017 Oct;26(5):1116-1129. doi: 10.1007/s10897-017-0090-y. Epub 2017 Mar 29.
Recent advances in next generation sequencing have enabled panel gene testing, or simultaneous testing for mutations in multiple genes for a clinical condition. With more extensive and widespread genetic testing, there will be increased detection of genes with moderate penetrance without established clinical guidelines and of variants of uncertain significance (VUS), or genetic variants unknown to either be disease-causing or benign. This study surveyed 232 patients who underwent genetic counseling for hereditary breast and ovarian cancer to examine the impact of panel gene testing on psychological outcomes, patient understanding, and utilization of genetic information. The survey used standardized instruments including the Impact of Event Scale (IES), Multidimensional Impact of Cancer Risk Assessment (MICRA), Satisfaction with Decision Instrument (SWD), Ambiguity Tolerance Scale (AT-20), genetics knowledge, and utilization of genetic test results. Study results suggested that unaffected individuals with a family history of breast or ovarian cancer who received positive results were most significantly impacted by intrusive thoughts, avoidance, and distress. However, scores were also modestly elevated among unaffected patients with a family history of breast and ovarian cancer who received VUS, highlighting the impact of ambiguous results that are frequent among patients undergoing genetic testing with large panels of genes. Potential risk factors for increased genetic testing-specific distress in this study included younger age, black or African American race, Hispanic origin, lower education level, and lower genetic knowledge and highlight the need for developing strategies to provide effective counseling and education to these communities, particularly when genetic testing utilizes gene panels that more commonly return VUS. More detailed pre-test education and counseling may help patients appreciate the probability of various types of test results and how results would be used clinically, and allow them to make more informed decisions about the type of genetic testing to select.
新一代测序技术的最新进展使得基因组合检测成为可能，即针对某一临床病症同时检测多个基因的突变情况。随着基因检测更加广泛和普及，对于那些具有中等外显率但尚无既定临床指南的基因以及意义不明确的变异体（VUS），也就是那些未知是致病还是良性的基因变异体，将会有更多的检测发现。本研究调查了232名接受遗传性乳腺癌和卵巢癌遗传咨询的患者，以检验基因组合检测对心理结果、患者理解以及基因信息利用情况的影响。该调查使用了标准化工具，包括事件影响量表（IES）、癌症风险评估多维影响量表（MICRA）、决策满意度量表（SWD）、模糊容忍度量表（AT - 20）、遗传学知识以及基因检测结果的利用情况。研究结果表明，有乳腺癌或卵巢癌家族史的未患病个体若收到阳性检测结果，会受到侵入性思维、回避行为和痛苦情绪的显著影响。然而，有乳腺癌和卵巢癌家族史的未患病患者若收到VUS结果，其得分也会有适度升高，这凸显了在接受大量基因检测的患者中频繁出现的模糊结果的影响。本研究中基因检测特异性痛苦增加的潜在风险因素包括年龄较小、黑人或非裔美国人种族、西班牙裔血统、教育水平较低以及遗传学知识较少，这突出表明需要制定策略，为这些群体提供有效的咨询和教育，尤其是当基因检测使用的基因组合更常返回VUS结果时。更详细的检测前教育和咨询可能有助于患者了解各类检测结果的可能性以及结果将如何在临床上使用，并使他们能够就选择何种基因检测类型做出更明智的决定。
