Association of Rare Pathogenic DNA Variants for Familial Hypercholesterolemia, Hereditary Breast and Ovarian Cancer Syndrome, and Lynch Syndrome With Disease Risk in Adults According to Family History

摘要: Importance Pathogenic DNA variants associated with familial hypercholesterolemia, hereditary breast and ovarian cancer syndrome, Lynch syndrome are widely recognized as clinically important actionable when identified, leading some clinicians to recommend population-wide genomic screening. Objectives To assess the prevalence clinical importance of pathogenic or likely each 3 conditions (familial syndrome) within context contemporary care. Design, Setting, Participants This cohort study used gene-sequencing data from 49 738 participants in UK Biobank who were recruited 22 sites across between March 21, 2006, October 1, 2010. Inpatient hospital date back 1977; registry data, 1957; death 2006. Statistical analysis was performed July 22, 2019, November 15, 2019. Exposures classified by a laboratory geneticist. Main Outcomes Measures Composite end point specific condition based on atherosclerotic cardiovascular disease events for colorectal uterine syndrome. Results Among (mean [SD] age, 57 [8] years; 27 144 female [55%]), 441 (0.9%) harbored variant any conditions, including 131 (0.3%) 235 (0.5%) 76 (0.2%) Presence these increased risk disease: 28 carriers (21.4%) vs 4663 49 607 noncarriers (9.4%) developed disease; 32 116 (27.6%) 2080 27 028 (7.7%) cancers; 17 (22.4%) 929 49 662 (1.9%) cancer. The predicted probability at age 75 years despite care 45.3% 41.1% 38.3% Across 39.7% (175 441) reported family history 23.2% (34 517 148 772) noncarriers. Conclusions Relevance findings suggest that approximately 1% middle-aged adult population conditions. These an not reliably detected history.