A 20-year perspective on the International Fanconi Anemia Registry (IFAR)
A 20-year perspective on the International Fanconi Anemia Registry (IFAR)
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DOI：
10.1182/blood-2002-07-2170
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发表时间：
2003-02-15
期刊：
影响因子：
20.3
通讯作者：
Auerbach, AD
中科院分区：
文献类型：
--
作者：
Kutler, DI;Singh, B;Auerbach, AD
范可尼贫血（IFA）是一种常染色体隐性遗传疾病，其特征是细胞对DNA交联剂的超敏反应和癌症易感性。共济失调-毛细血管扩张突变蛋白ATM和乳腺癌易感蛋白BRCA 1和BRCA 2（鉴定为FANCD 1）与其他已知FA蛋白相互作用的最新证据表明，FA蛋白在DNA修复/重组和细胞周期控制中具有重要作用。国际范可尼贫血登记（IFAR），前瞻性收集的数据库FA患者，使我们有独特的机会来分析这种罕见的，临床异质性疾病的自然史，在大量的患者。在本研究的754例受试者中，601例（80%）发生骨髓衰竭（BMF），173例（23%）共发生199例肿瘤。在这些肿瘤中，120例（60%）为血液学肿瘤，79例（40%）为非血液学肿瘤。发生BMF和血液及非血液肿瘤的风险随着年龄的增长而增加，40岁时的累积发生率分别为90%、33%和28%。单因素分析显示，与A组和G组相比，互补组C的BMF发生时间明显早于A组和G组，生存率较差;然而，这些组之间的血液学或非血液学肿瘤发展时间没有显著差异。总生存时间的多变量分析显示，FANCC突变（P = 0.007）和造血干细胞移植（P = <0.0001）定义了一个低风险亚组。这项对IFAR中登记的患者进行的20年研究结果提供了信息，可以更好地预测结果，并帮助临床医生做出有关主要治疗方式的决定。(C)2003年，美国血液学会。
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.