CDH1 pathogenic variants confer a markedly elevated lifetime risk of developing diffuse gastric cancer (DGC) and lobular breast cancer (LBC). The aim of this study was to evaluate the prevalence and clinical impact of CDH1 pathogenic variants in the unselected and ancestrally diverse BioMe Biobank. We evaluated exome sequence data from 30,223 adult BioMe participants to identify CDH1 positive individuals, defined as those harboring a variant previously classified as pathogenic or likely pathogenic or a predicted loss-of-function variant in CDH1. We reviewed electronic health records and BioMe enrollment surveys for personal and family history of malignancy and evidence of prior clinical genetic testing. Using a genomics-first approach, we identified 6 CDH1 positive individuals in BioMe (~ 1 in 5000). CDH1 positive individuals had a median age of 42 years (range 35–62 years), all were non-European by self-report, and one was female. None had evidence of either a personal or family history of DGC or LBC. Our findings suggest a low risk of DGC and LBC in unselected patients harboring a pathogenic variant in CDH1. Knowledge of CDH1-related cancer risk in individuals with no personal or family history may better inform surveillance and prophylactic measures.

CDH1致病性变异会显着增加患弥漫性胃癌 (DGC) 和小叶性乳腺癌 (LBC) 的终生风险。本研究的目的是评估CDH1致病变异在未经选择和祖先多样化的 Bio Me Biobank 中的流行率和临床影响。我们评估了来自 30,223 名成年 Bio Me参与者的外显子组序列数据，以确定CDH1阳性个体，这些个体被定义为携带先前被归类为致病性或可能致病性或预测的CDH1功能丧失变异的变异。我们审查了电子健康记录和 Bio Me针对个人和家族恶性肿瘤史和先前临床基因检测证据的登记调查。使用基因组学优先的方法，我们在 Bio Me中确定了 6 个CDH1阳性个体（约 5000 人中有 1 个）。CDH1阳性个体的中位年龄为 42 岁（范围 35-62 岁），根据自我报告均为非欧洲人，其中一名为女性。没有人有 DGC 或 LBC 个人或家族病史的证据。我们的研究结果表明，在未经选择的携带CDH1致病性变异的患者中，DGC 和 LBC 的风险较低。对没有个人或家族史的个体的CDH1相关癌症风险的了解可能会更好地为监测和预防措施提供信息。