CDH1 pathogenic variants and cancer risk in an unselected patient population

AbstractCDH1 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 ofCDH1 pathogenic variants in the unselected and ancestrally diverse BioMe Biobank. We evaluated exome sequence data from 30,223 adult BioMe participants to identifyCDH1 positive individuals, defined as those harboring a variant previously classified as pathogenic or likely pathogenic or a predicted loss-of-function variant inCDH1. 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 6CDH1 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 inCDH1. Knowledge ofCDH1-related cancer risk in individuals with no personal or family history may better inform surveillance and prophylactic measures.
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research