USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California, USA.
Department of Human Genetics and Genetic Counseling, Keck Graduate Institute, Claremont, California, USA.
J Genet Couns. 2023 Jun;32(3):706-716. doi: 10.1002/jgc4.1680. Epub 2023 Feb 6.
Research suggests variants of uncertain significance (VUSs) present a variety of challenges for genetic counselors (GCs), nongenetics clinicians, and patients. Multigene cancer panels reveal more VUSs than single gene testing as a result of the increase in the number of genes being tested. This study surveyed 87 clinical cancer GCs involved with direct patient care and 19 laboratory GCs who provide guidance to clinicians regarding genetic test results about their attitudes on various options for the reporting of VUSs by laboratories for broad multigene cancer panels. Independent samples t-tests were utilized to compare the two groups. Based on a six-point Likert-type scale (1 = Strongly Disagree to 6 = Strongly Agree), clinical cancer GCs (M = 5.4; SD = 0.8) and laboratory GCs (M = 5.2; SD = 0.9) agreed overall that VUSs should be reported (p = 0.44; Cohen's d = 0.21). When asked about specific reporting options, both clinical cancer GCs (M = 1.9; SD = 1.1) and laboratory GCs (M = 2.1; SD = 1.4) disagreed that VUSs should be reported only for genes related to the indication for testing (p = 0.50; Cohen's d = 0.17). Overall, most GCs felt clinicians should not choose whether VUSs should be reported on genetic test results, with clinical cancer GCs (M = 1.9; SD = 1.3) feeling more strongly against it than laboratory GCs (M = 3.1; SD = 1.4; p = 0.002; Cohen's d = 0.88). Generally, GCs were more in favor of VUSs not being reported for population-based screening, with laboratory GCs (M = 4.7; SD = 0.8) agreeing more with that practice than clinical cancer GCs (M = 3.7; SD = 1.4; p = 0.001; Cohen's d = 0.80). Both clinical cancer GCs (M = 4.1; SD = 1.2) and laboratory GCs (M = 3.9; SD = 1.2) agreed additional guidelines on how to approach VUSs in clinical practice should be developed (p = 0.54; Cohen's d = 0.17). While most GCs supported the reporting of VUSs overall, our analyses suggest clinical cancer and laboratory GCs may have different attitudes toward specific VUS-related reporting options. Further research is needed to elucidate GC preferences to help inform best practices for the reporting of VUSs. The development of additional standardized guidelines on how to approach VUSs would further support clinical practice.
研究表明,不确定意义的变异(VUS)给遗传咨询师(GCs)、非遗传临床医生和患者带来了各种挑战。多基因癌症面板由于检测基因数量的增加,比单基因检测揭示了更多的 VUS。本研究调查了 87 名参与直接患者护理的临床癌症 GCs 和 19 名提供遗传测试结果指导的实验室 GCs,了解他们对实验室报告广泛多基因癌症面板的 VUS 的各种选择的态度。利用独立样本 t 检验比较两组。基于六点李克特量表(1 = 强烈不同意到 6 = 强烈同意),临床癌症 GCs(M = 5.4;SD = 0.8)和实验室 GCs(M = 5.2;SD = 0.9)总体上同意报告 VUS(p = 0.44;Cohen's d = 0.21)。当被问及具体的报告选项时,临床癌症 GCs(M = 1.9;SD = 1.1)和实验室 GCs(M = 2.1;SD = 1.4)均不同意仅报告与测试指征相关的基因的 VUS(p = 0.50;Cohen's d = 0.17)。总体而言,大多数 GCs 认为临床医生不应该选择是否报告遗传测试结果中的 VUS,临床癌症 GCs(M = 1.9;SD = 1.3)比实验室 GCs(M = 3.1;SD = 1.4;p = 0.002;Cohen's d = 0.88)更强烈地反对这一观点。一般来说,GCs 更倾向于不报告基于人群的筛查中的 VUS,实验室 GCs(M = 4.7;SD = 0.8)比临床癌症 GCs(M = 3.7;SD = 1.4;p = 0.001;Cohen's d = 0.80)更同意这种做法。临床癌症 GCs(M = 4.1;SD = 1.2)和实验室 GCs(M = 3.9;SD = 1.2)均同意应制定更多关于如何在临床实践中处理 VUS 的指南(p = 0.54;Cohen's d = 0.17)。尽管大多数 GCs 总体上支持报告 VUS,但我们的分析表明,临床癌症和实验室 GCs 可能对特定的 VUS 相关报告选项有不同的态度。需要进一步研究以阐明 GCs 的偏好,以帮助为 VUS 的报告提供最佳实践。额外的标准化指南的制定将进一步支持临床实践。