BRCA1 and BRCA2 population screening in Latvia: feasibility, engagement, and early lessons from a pilot study.

Pathogenic variants in BRCA1 and BRCA2 account for the majority of hereditary breast and ovarian cancer (HBOC) cases, and are associated with substantial morbidity, mortality, and economic burden. Population screening for BRCA1 and BRCA2 pathogenic variants (PVs) may enable cancer prevention and reduce downstream costs and mortality. The feasibility pilot of BRCA1 and BRCA2 PV population screening in Latvia was conducted among cancer-free females aged 25-59 years, using digital recruitment tools and saliva-based BRCA1 and BRCA2 gene NGS with CNV analysis. Psychological impact was assessed using PHQ-9 and GAD-7. After 3,438 email invitations and media campaigns, 536 participants provided samples. Eight PVs were identified, and all carriers reported at least one affected first-degree relative. PHQ-9 and GAD-7 scores showed no significant pre- and post-testing differences. Saliva-based population screening for BRCA1 and BRCA2 pathogenic variants is feasible in Latvia showing considerable (1.5%) frequency of PVs, acceptable psychological outcomes, but requires improved engagement strategies and equitable access pathways.