A 20-year perspective on the International Fanconi Anemia Registry (IFAR) Journal Article
| Authors: | Kutler, D. I.; Singh, B.; Satagopan, J.; Batish, S. D.; Berwick, M.; Giampietro, P. F.; Hanenberg, H.; Auerbach, A. D. |
| Article Title: | A 20-year perspective on the International Fanconi Anemia Registry (IFAR) |
| Abstract: | Fanconi anemia (IFA) is an autosomal recessive disorder characterized by cellular hypersensitivity to DNA cross-linking agents and cancer predisposition. Recent evidence for the interactions of ataxia-telangiectasia mutated protein ATM and breast cancer susceptibility proteins BRCA1 and BRCA2 (identified as FANCD1) with other known FA proteins suggests that FA proteins have a significant role in DNA repair/recombination and cell cycle control. The International Fanconi Anemia Registry (IFAR), a prospectively collected database of FA patients, allows us the unique opportunity to analyze the natural history of this rare, clinically heterogeneous disorder in a large number of patients. Of the 754 subjects in this study, 601 (80%) experienced the onset of bone marrow failure (BMF), and 173 (23%) had a total of 199 neoplasms. Of these neoplasms, 120 (60%) were hematologic and 79 (40%) were nonhematologic. The risk of developing BMF and hematologic and nonhematologic neoplasms increased with advancing age with a 90%, 33%, and 28% cumulative incidence, respectively, by 40 years of age. Univariate analysis revealed a significantly earlier onset of BMF and poorer survival for complementation group C compared with groups A and G.; however, there was no significant difference in the time to hematologic or nonhematologic neoplasm development between these groups. Multivariate analysis of overall survival time shows that FANCC mutations (P = .007) and hematopoietic stem cell transplantation (P = < .0001) define a poor-risk subgroup. The results of this study of patients registered in the IFAR over a 20-year period provide information that will enable better prediction of outcome and aid clinicians with decisions regarding major therapeutic modalities. (C) 2003 by The American Society of Hematology. |
| Keywords: | mutation; proteins; gene; tumors; diagnosis; malignancies; cloning; complementation; nuclear-complex; fac |
| Journal Title: | Blood |
| Volume: | 101 |
| Issue: | 4 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2003-02-15 |
| Start Page: | 1249 |
| End Page: | 1256 |
| Language: | English |
| ACCESSION: | WOS:000180846700010 |
| DOI: | 10.1182/blood-2002-07-2170 |
| PROVIDER: | wos |
| PUBMED: | 12393516 |
| Notes: | Article -- Source: Wos |
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