Purpose

Three genetic conditions—hereditary breast and ovarian cancer syndrome, Lynch syndrome, and familial hypercholesterolemia—have tier 1 evidence for interventions that reduce morbidity and mortality, prompting proposals to screen unselected populations for these conditions. We examined the impact of genomic screening on risk management and early detection in an unselected population.

Methods

Observational study of electronic health records (EHR) among individuals in whom a pathogenic/likely pathogenic variant in a tier 1 gene was discovered through Geisinger’s MyCode project. EHR of all eligible participants was evaluated for a prior genetic diagnosis and, among participants without such a diagnosis, relevant personal/family history, postdisclosure clinical diagnoses, and postdisclosure risk management.

Results

Eighty-seven percent of participants (305/351) did not have a prior genetic diagnosis of their tier 1 result. Of these, 65% had EHR evidence of relevant personal and/or family history of disease. Of 255 individuals eligible to have risk management, 70% (n = 179) had a recommended risk management procedure after results disclosure. Thirteen percent of participants (41/305) received a relevant clinical diagnosis after results disclosure.

Conclusion

Genomic screening programs can identify previously unrecognized individuals at increased risk of cancer and heart disease and facilitate risk management and early cancer detection.

中文翻译：

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针对可操作遗传状况的基因组筛查计划的临床结果。

目的

三种遗传疾病——遗传性乳腺癌和卵巢癌综合征、Lynch 综合征和家族性高胆固醇血症——具有降低发病率和死亡率的干预措施的 1 级证据，促使人们建议对未选择的人群进行这些疾病的筛查。我们检查了基因组筛查对未选择人群的风险管理和早期检测的影响。

方法

对通过 Geisinger 的 MyCode 项目发现 1 级基因的致病/可能致病变异的个体进行电子健康记录 (EHR) 的观察性研究。对所有符合条件的参与者的 EHR 进行了先前基因诊断的评估，并在没有此类诊断的参与者中评估了相关的个人/家族史、披露后的临床诊断和披露后的风险管理。

结果

87% 的参与者 (305/351) 没有对他们的 1 级结果进行先前的基因诊断。其中，65% 有相关个人和/或家族疾病史的 EHR 证据。在 255 名有资格进行风险管理的个人中，70%（n  = 179）在结果披露后有推荐的风险管理程序。结果披露后，13% 的参与者 (41/305) 接受了相关的临床诊断。

结论

基因组筛查计划可以识别以前未被识别的癌症和心脏病风险增加的个体，并促进风险管理和早期癌症检测。