Abstract：
BACKGROUND: Knowledge of the genetic mechanisms driving hereditary breast and ovarian cancer (HBOC) has recently expanded due to advances in gene sequencing technologies. Genetic testing for HBOC risk now involves multi-gene panel testing, which includes well characterized high-penetrance genes (e.g. BRCA1 and BRCA2), as well as moderate- and low-penetrance genes. Certain moderate and low penetrance genes are associated with limited data to inform cancer risk estimates and clinical management recommendations, which create new sources of genetic and clinical uncertainty for patients.
OBJECTIVE: The aim of this review is to evaluate the psychological and health behaviour outcomes associated with multi-gene panel testing for HBOC risk. The search was developed in collaboration with an Information Specialist (Princess Margaret Cancer Centre) and conducted in the following databases: MEDLINE, EMBASE, EMCare, PsycINFO, Epub Ahead of Publication.
RESULTS: Similar to the BRCA1/2 literature, individuals with a pathogenic variant (PV) reported higher levels of testing-related concerns and cancer-specific distress, as well as higher uptake of prophylactic surgery in both affected and unaffected individuals compared to those with variant of uncertain significance (VUS) or negative result. A single study demonstrated that individuals with a PV in a moderate penetrance gene reported higher rates of cancer worry, genetic testing concerns and cancer-related distress when compared to women with high penetrance PV. Analysis of cancer screening and prevention outcomes based upon gene penetrance were limited to two studies, with conflicting findings.
CONCLUSIONS: The findings in this review emphasize the need for studies examining psychological and health behavior outcomes associated with panel testing to include between group differences based upon both variant pathogenicity and gene penetrance. Future studies evaluating the impact of gene penetrance on patient-reported and clinical outcomes will require large samples to be powered for these analyses given that a limited number of tested individuals are found to have a PV.
OBJECTIVE: The aim of this review is to evaluate the psychological and health behaviour outcomes associated with multi-gene panel testing for HBOC risk. The search was developed in collaboration with an Information Specialist (Princess Margaret Cancer Centre) and conducted in the following databases: MEDLINE, EMBASE, EMCare, PsycINFO, Epub Ahead of Publication.
RESULTS: Similar to the BRCA1/2 literature, individuals with a pathogenic variant (PV) reported higher levels of testing-related concerns and cancer-specific distress, as well as higher uptake of prophylactic surgery in both affected and unaffected individuals compared to those with variant of uncertain significance (VUS) or negative result. A single study demonstrated that individuals with a PV in a moderate penetrance gene reported higher rates of cancer worry, genetic testing concerns and cancer-related distress when compared to women with high penetrance PV. Analysis of cancer screening and prevention outcomes based upon gene penetrance were limited to two studies, with conflicting findings.
CONCLUSIONS: The findings in this review emphasize the need for studies examining psychological and health behavior outcomes associated with panel testing to include between group differences based upon both variant pathogenicity and gene penetrance. Future studies evaluating the impact of gene penetrance on patient-reported and clinical outcomes will require large samples to be powered for these analyses given that a limited number of tested individuals are found to have a PV.
摘要：
背景：由于基因测序技术的进步，最近对驱动遗传性乳腺癌和卵巢癌（HBOC）的遗传机制的了解有所增加。HBOC风险的基因检测现在涉及多基因小组检测，其中包括特征良好的高外显率基因（例如BRCA1和BRCA2），以及中等和低外显率基因。某些中等和低外显率基因与有限的数据相关，以告知癌症风险估计和临床管理建议。这为患者创造了新的遗传和临床不确定性来源。
目的：本综述的目的是评估与HBOC风险的多基因小组测试相关的心理和健康行为结果。搜索是与信息专家（玛格丽特公主癌症中心）合作开发的，并在以下数据库中进行：MEDLINE，EMBASE,EMCare,PsycINFO,Epub在出版之前。
结果：与BRCA1/2文献类似，具有致病性变异（PV）的个体报告了更高水平的与测试相关的担忧和癌症特异性困扰，以及与具有不确定意义（VUS）或阴性结果的个体相比，受影响和未受影响的个体对预防性手术的摄取更高。一项研究表明，具有中等外显率基因的PV的个体报告了更高的癌症担忧率，与高外显率PV的女性相比，基因检测问题和癌症相关的痛苦。基于基因外显率的癌症筛查和预防结果分析仅限于两项研究，矛盾的发现。
结论：本综述的研究结果强调需要研究与小组测试相关的心理和健康行为结果，以包括基于变异致病性和基因外显率的组间差异。未来评估基因外显率对患者报告和临床结果的影响的研究将需要大样本进行这些分析，因为发现有限数量的测试个体具有PV。
目的：本综述的目的是评估与HBOC风险的多基因小组测试相关的心理和健康行为结果。搜索是与信息专家（玛格丽特公主癌症中心）合作开发的，并在以下数据库中进行：MEDLINE，EMBASE,EMCare,PsycINFO,Epub在出版之前。
结果：与BRCA1/2文献类似，具有致病性变异（PV）的个体报告了更高水平的与测试相关的担忧和癌症特异性困扰，以及与具有不确定意义（VUS）或阴性结果的个体相比，受影响和未受影响的个体对预防性手术的摄取更高。一项研究表明，具有中等外显率基因的PV的个体报告了更高的癌症担忧率，与高外显率PV的女性相比，基因检测问题和癌症相关的痛苦。基于基因外显率的癌症筛查和预防结果分析仅限于两项研究，矛盾的发现。
结论：本综述的研究结果强调需要研究与小组测试相关的心理和健康行为结果，以包括基于变异致病性和基因外显率的组间差异。未来评估基因外显率对患者报告和临床结果的影响的研究将需要大样本进行这些分析，因为发现有限数量的测试个体具有PV。
