A recent study has shown that heterozygous pathogenic germline variants in BRCA1, BRCA2, and mismatch repair genes attribute to cancer risk with reduced penetrance in children and young adults. The results of this study were published in the Journal of the National Cancer Institute.
A meta-analysis of 11 studies was performed that included comprehensive germline testing for children and adolescents with cancer. Pathogenic variants (PVs) in genes of interest were compared with 2 control groups. Among 3975 children and adolescents having cancer, statistically significant associations for risk of cancer were observed for PVs in BRCA1, BRCA2, and mismatch repair genes. Similar findings were confirmed in 1664 pediatric cancer patients.
Thus, this study denotes that heterozygous PVs in BRCA1 and BRCA2 and mismatch repair genes like PALB2, ATM, CHEK2, MSH2, MSH6, MLH1, and PMS2 in children and adolescents play a role in cancer risk with reduced penetrance.
- Kratz, C. P., Smirnov, D., Autry, R., et al. (2022). Heterozygous BRCA1 and BRCA2 and Mismatch Repair Gene Pathogenic Variants in Children and Adolescents With Cancer. Journal of the National Cancer Institute. https://pubmed.ncbi.nlm.nih.gov/35980168/