Submitted December 3, 2008
Accepted March 9, 2009
Cancer in dyskeratosis congenita
Blanche P. Alter*, Neelam Giri, Sharon A. Savage, and Philip S. Rosenberg
Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, United States
Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, United States
* Corresponding author; email: alterb{at}mail.nih.gov.
Dyskeratosis congenita (DC) is a rare inherited bone marrow failure syndrome. The spectrum of cancer susceptibility in this disorder of telomere biology has not been described. There were more than 500 cases of DC reported in the literature from 1910 - 2008; the National Cancer Institute's (NCI) prospective DC cohort enrolled 50 cases from 2002 - 2007. Sixty cancers were reported in 52 literature cases, while 7 occurred among patients in the NCI DC Cohort. The two cohorts were comparable in their median overall survival (42 years) and cumulative incidence of cancer (40-50% by age 50 years). The most frequent solid tumors were head and neck squamous cell carcinomas (40% of patients in either cohort), followed by skin and anorectal cancer. The ratio of observed to expected cancers (O/E ratio) in the NCI cohort was 11-fold compared with the general population (p<0.05). Significantly elevated O/E ratios were 1154 for tongue cancer and 195 for acute myeloid leukemia. Survival after bone marrow transplantation for aplastic anemia or leukemia was poor in both cohorts. The frequency and types of cancer in DC are surpassed only by those in Fanconi anemia (FA), indicating that FA and DC have similar high risks of adverse hematologic and neoplastic events, and should be counseled and monitored similarly.
