Childhood cancer in families with and without BRCA1 or BRCA2 mutations ascertained at a high-risk breast cancer clinic.
BACKGROUND
Germline mutations in the BRCA1 and BRCA2 genes are associated with breast cancer, ovarian cancer and other malignancies. Biallelic mutations of BRCA2 are a cause of Fanconi anemia and characteristic childhood cancers. We undertook this study to evaluate the contribution of familial BRCA mutations to childhood cancer in hereditary breast cancer families.


METHODS
We compared the prevalence of childhood cancers in 379 families with BRCA1 or BRCA2 mutations and 426 families without mutations. All families were ascertained at a high-risk breast cancer clinic. Our study included first- through fourth-degree relatives of BRCA mutation carriers and cancer-affected individuals with negative testing for BRCA mutations. The primary endpoint was any case of childhood cancer (diagnosed < age 21).


RESULTS
20 cases of childhood cancer occurred in 379 families with BRCA1 or BRCA2 mutations and 35 cases of childhood cancer occurred in 426 families with negative mutation testing (p = 0.12). Nine childhood cancers occurred in 240 families with BRCA1 mutations, and 11 childhood cancers occurred in 141 families with BRCA2 mutations (p = 0.1). 13 of 18 families with childhood cancer and BRCA1 or BRCA2 mutations (72%) and 13 of 31 families with childhood cancer and negative mutation testing (42%) met the Birch criteria for Li-Fraumeni like syndrome (LFL).


CONCLUSIONS
In this retrospective analysis, heterozygous BRCA1 and BRCA2 mutations were not a risk factor for childhood cancer in hereditary breast cancer families. These data support the current practice of delaying BRCA mutation testing until adulthood.
Brooks
Gabriel A
GA
School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Stopfer
Jill E
JE
Erlichman
Julie
J
Davidson
Rebecca
R
Nathanson
Katherine L
KL
Domchek
Susan M
SM
D000293:Adolescent; D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics; D010375:Pedigree; D012189:Retrospective Studies