A follow-up cohort study on secondary findings in cancer predisposition genes from 20,205 Chinese individuals.

Secondary pathogenic variants in 28 cancer predisposition genes

The increasing use of sequencing raises detection of secondary findings (SFs) in cancer predisposition genes, but their clinical follow-up in paediatrics remains poorly documented. The authors retrospectively analysed exome data from 20,205 non-cancer individuals tested at Shanghai Children's Medical Center (2014-2025) for 28 predefined genes. Sixty-seven pathogenic or likely pathogenic variants were identified in 84 probands, an SF frequency of 0.42%. The genes involved were mainly BRCA2 (35%), PALB2 (22%), BRCA1 (20%), PMS2 (13%) and MSH6 (6%), with 78% loss-of-function variants and 99% inherited. Among 33 questionnaire respondents, 13 reported anxiety, yet all perceived health-management benefits.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

Returning secondary findings enables genetic counselling, cascade testing and risk management for probands and relatives, a clear benefit despite the anxiety generated. The predominance of BRCA2, PALB2 and BRCA1 in a non-cancer paediatric population raises the concrete question of age-appropriate return strategies. The curated pedigrees provide a useful resource for penetrance research.

Analysis by Dr Thibaut Benquey