Fanconi anaemia (FA), dyskeratosis congenita (DC), Diamond-Blackfan anaemia 
(DBA), and Shwachman-Diamond syndrome (SDS) comprise major inherited bone marrow 
failure syndromes (IBMFS). Adverse events include severe bone marrow failure 
(BMF), myelodysplastic syndrome (MDS), acute myeloid leukaemia (AML), and solid 
tumours (ST). The natural history of FA is well characterised; hazard rates in 
the other syndromes have not yet been quantified. An open cohort was established 
at the National Cancer Institute (NCI) in 2002. Patients enrolled prior to 
December, 2007 were followed up to December, 2008. Diagnoses were confirmed with 
standard tests. Age-associated risks of adverse events were calculated. Most 
patients in each syndrome survived to young adulthood. Patients with FA had 
earlier onset of cancers, need for stem cell transplant, and death; followed by 
DC; DBA and SDS were mildest. While FA and DC patients had markedly increased 
risks of cancer, AML and MDS, there were no cases of leukaemia in DBA or SDS 
patients. The NCI cohort provides the first direct quantitative comparison of 
timing and magnitude of cancer risk in the IBMFS. The findings demonstrate that 
both FA and DC are major cancer susceptibility syndromes. The IBMFS, 
historically considered paediatric disorders, have important management 
implications for physicians treating adult patients.