Highlight
– Rare pathogenic variants (RPVs) in 16 established cancer predisposition genes increase the risk of single and multiple primary cancers.
– This large population-based study used whole-exome sequencing data from over 180,000 UK Biobank participants.
– Individuals carrying RPVs showed significantly elevated odds for cancer, particularly multiple cancer diagnoses.
– Results underscore the clinical utility of multigene panel testing beyond family-based or clinically ascertained cases.