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题目:: Childhood cancer in families with and without germline BRCA1/2 mutations ascertained at a high-risk breast cancer clinic.
作者:: Brooks(G A),Stopfer(J E),Erlichman(J),Davidson(R),Nathanson(K L),Domchek(S M)
状态:: 发布时间2016-12-13 , 更新时间 2016-12-13
期刊:: J Clin Oncol
摘要:: 10013 Background: Germline mutations in the BRCA1 and BRCA2 genes (BRCA1/2) 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 heterozygous BRCA1/2 mutations to childhood cancer in hereditary breast cancer families.,We conducted a retrospective cohort study to compare the prevalence of childhood cancers among 379 families with BRCA1/2 mutations and 426 families without known mutations. All families were ascertained at a high-risk breast cancer clinic. Our study and comparison cohorts included first- through fourth-degree relatives of cancer-affected mutation carriers and cancer-affected individuals with negative full sequencing for BRCA1/2 mutations. The primary endpoint was any case of childhood cancer (diagnosed <age 21) as recorded in the family history. Results were analyzed using Fisher's exact test.,20 cases of childhood cancer were observed in 379 families with BRCA1/2 mutations and 35 cases of childhood cancer were observed in 426 families with negative mutation testing (p = 0.12). Apart from two very early-onset breast cancers, the types of childhood cancers occurring in the BRCA1/2 mutation positive families were similar to those occurring in the mutation negative families and in the general population. 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 BRCA1/2 mutation positive families with cases of childhood cancer (72%) and 13 of 31 families with childhood cancer cases and negative mutation testing (42%) met the Birch clinical criteria for Li-Fraumeni like syndrome (LFL); no individual has undergone testing for germline TP53 mutations.,Heterozygous BRCA1/2 mutations do not appear to be a significant risk factor for childhood cancer in hereditary breast cancer families. This observation supports the current practice of delaying BRCA1/2 mutation testing until candidates reach adulthood. Although many families in both groups met criteria for LFL, the clinical significance of this finding is uncertain. No significant financial relationships to disclose.
语言:: eng
DOI:

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