Higher occurrence of childhood cancer in families with germline mutations in BRCA2, MMR and CDKN2A genes

The contribution of hereditary factors for development of childhood tumors is limited to some few known syndromes associated with predominance of tumors in childhood. Occurrence of childhood tumors in hereditary cancer syndromes such as BRCA1/2 associated breast and ovarian cancer, DNA-mismatch repair (MMR) genes associated hereditary non polyposis colorectal cancer and CDKN2A associated familial malignant melanoma are very little studied. Herein we report the prevalence of childhood tumors (diagnosed <= 18 years of age) in families identified with mutation in the BRCA1/2, MMR and CDKN2A genes. Using pedigrees at the Regional Oncogenetic Clinic at Lund University Hospital, the prevalence of childhood cancer was estimated in families with mutations in the BRCA1 (n = 98), BRCA2 (n = 43) MMR (MLH1, MSH2 MSH6) (n = 31) and CDKN2A (n = 15) genes in comparison with population based control families (n = 854). Compared with the control group, a significantly higher prevalence of childhood cancer was found in families with mutations in BRCA2 (9.3% vs. 0.8% P = 0.001), MMR genes (19.4% vs. 0.8% P < 0.001) and CDKN2A (20.0% vs. 0.8% P < 0.001), but not in families with BRCA1 mutations (1.0% vs. 0.8% P = 0.6). Further analyses showed an increased risk for childhood tumors in families with mutations in BRCA2 (OR 12.4; 95% CI 3.5-44.1), MMR genes (OR 29.0; 95% CI 9.1-92.6), and CDKN2A (OR 30.2; 95% CI 7.0-131.1). This study suggests that the risk for childhood tumors is increased in families with germline mutations in the BRCA2, MMR and CDKN2A genes.