TY  - JOUR
AU  - Kratz, Christian P
AU  - Smirnov, Dmitrii
AU  - Autry, Robert
AU  - Jäger, Natalie
AU  - Waszak, Sebastian M
AU  - Großhennig, Anika
AU  - Berutti, Riccardo
AU  - Wendorff, Mareike
AU  - Hainaut, Pierre
AU  - Pfister, Stefan
AU  - Prokisch, Holger
AU  - Ripperger, Tim
AU  - Malkin, David
TI  - Heterozygous BRCA1/2 and Mismatch Repair Gene Pathogenic Variants in Children and Adolescents with Cancer.
JO  - Journal of the National Cancer Institute
VL  - 114
IS  - 11
SN  - 0027-8874
CY  - Oxford
PB  - Oxford Univ. Press
M1  - DKFZ-2022-01906
SP  - 1523-1532
PY  - 2022
N1  - 2022 Nov 14;114(11):1523-1532
AB  - Genetic predisposition is a significant cause of cancer, yet little is known about the role of 'adult cancer predisposition syndromes' in childhood cancer. We examined the extent to which heterozygous pathogenic germline variants in BRCA1, BRCA2, PALB2, ATM, CHEK2, MSH2, MSH6, MLH1, and PMS2 contribute to cancer risk in children and adolescents.We conducted a meta-analysis of 11 studies that incorporated comprehensive germline testing for children and adolescents with cancer. ClinVar pathogenic/likely pathogenic variants (PVs) in genes of interest were compared to two control groups. Results were validated in a cohort of mainly European cases and controls. We employed the Proxy External Controls Association Test to account for different pipelines.Among 3,975 children/adolescents with cancer, significant associations with cancer risk were observed for PVs in BRCA1/2 (26 PVs vs 63 PVs among 27,501 controls, OR 2.78, 95
LB  - PUB:(DE-HGF)16
C6  - pmid:35980168
DO  - DOI:10.1093/jnci/djac151
UR  - https://inrepo02.dkfz.de/record/181263
ER  -