PURPOSE: Despite recognition that second @entity5 (SMNs) contribute significantly to mortality after the successful treatment of @entity978 ( @entity978 ), little is known about the molecular events leading to secondary @entity5 . Factors contributing to second @entity5 risk include the carcinogenic effects of ionizing radiation and chemotherapy, in combination with possible host susceptibility. To clarify whether host genetic factors contribute to secondary tumorigenesis, we performed mutational analyses of the @entity876 , @entity5345 , and @entity2674 @entity5 suppressor genes in a cohort of 44 @entity978 @entity1 developing one or more SMN. @entity1 AND METHODS: Family @entity5 histories and constitutional DNA samples were obtained from 44 @entity978 @entity1 with SMNs identified. Using DNA-based sequencing, we evaluated the @entity876 gene in all 44 @entity1 . Nineteen female @entity1 developing one or more @entity0 were also analyzed for mutations in the @entity5345 and @entity2674 breast @entity5 -susceptibility genes. RESULTS: Nineteen @entity1 (43%) had more than one SMN, and 12 @entity1 (27%) had a positive family history of @entity5 . One of 44 @entity1 tested for @entity876 harbored a novel homozygous germline abnormality. One of 19 @entity1 tested for @entity2674 carried a previously described heterozygous inactivating mutation. We identified no germline @entity5345 mutations. CONCLUSION: Despite features suggestive of genetic predisposition, the @entity876 , @entity5345 , and @entity2674 genes were not frequently mutated in this cohort of @entity978 @entity1 developing SMNs. Larger studies of these genes or investigations of other genes involved in cellular DNA damage response pathways may identify host genetic factors that contribute to secondary tumorigenesis.

@entity876 , @entity5345 , and @entity2674 @entity5 suppressor genes are not commonly mutated in survivors of @entity978 with second XXXX .

@entity1 :: ('9606', 'Species') :: ['patients', 'PATIENTS'] @entity0 :: ('MESH:D001943', 'Disease') :: ['secondary breast cancer'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'cancer', 'malignant neoplasms', 'tumors'] @entity5345 :: ('672', 'Gene') :: ['BRCA1'] @entity2674 :: ('675', 'Gene') :: ['BRCA2'] @entity876 :: ('7157', 'Gene') :: ['TP53'] @entity978 :: ('MESH:D006689', 'Disease') :: ['HD', "Hodgkin's disease"]
@entity5 :: (MESH:D009369,Disease) :: ['primary neoplasms']
