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Dutzmann CM, Spix C, Popp I, et al. Cancer in Children With Fanconi Anemia and Ataxia-Telangiectasia-A Nationwide Register-Based Cohort Study in Germany. J Clin Oncol. 2021;40(1):32-39doi: 10.1200/JCO.21.01495.
Dutzmann, C. M., Spix, C., Popp, I., Kaiser, M., Erdmann, F., Erlacher, M., Dörk, T., Schindler, D., Kalb, R., & Kratz, C. P. (2022). Cancer in Children With Fanconi Anemia and Ataxia-Telangiectasia-A Nationwide Register-Based Cohort Study in Germany. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 40(1), 32-39. https://doi.org/10.1200/JCO.21.01495
Dutzmann, Christina M, et al. "Cancer in Children With Fanconi Anemia and Ataxia-Telangiectasia-A Nationwide Register-Based Cohort Study in Germany." Journal of clinical oncology : official journal of the American Society of Clinical Oncology vol. 40,1 (2022): 32-39. doi: https://doi.org/10.1200/JCO.21.01495
Dutzmann CM, Spix C, Popp I, Kaiser M, Erdmann F, Erlacher M, Dörk T, Schindler D, Kalb R, Kratz CP. Cancer in Children With Fanconi Anemia and Ataxia-Telangiectasia-A Nationwide Register-Based Cohort Study in Germany. J Clin Oncol. 2022 Jan 01;40(1):32-39. doi: 10.1200/JCO.21.01495. Epub 2021 Oct 01. PMID: 34597127; PMCID: PMC8683217.
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J Clin Oncol. 2022 Jan 01;40(1):32-39. doi: 10.1200/JCO.21.01495. Epub 2021 Oct 01.

Cancer in Children With Fanconi Anemia and Ataxia-Telangiectasia-A Nationwide Register-Based Cohort Study in Germany.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

Christina M Dutzmann, Claudia Spix, Isabell Popp, Melanie Kaiser, Friederike Erdmann, Miriam Erlacher, Thilo Dörk, Detlev Schindler, Reinhard Kalb, Christian P Kratz

Affiliations

  1. Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.
  2. Division of Childhood Cancer Epidemiology, Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
  3. Department of Human Genetics, University of Würzburg, Biocenter, Würzburg, Germany.
  4. Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Germany.
  5. German Cancer Consortium (DKTK), Freiburg, Freiburg, Germany.
  6. German Cancer Research Center (DKFZ), Heidelberg, Germany.
  7. Department of Gynecology and Obstetrics, Hannover Medical School, Hannover, Germany.

PMID: 34597127 PMCID: PMC8683217 DOI: 10.1200/JCO.21.01495

Abstract

PURPOSE: Fanconi anemia (FA) and ataxia-telangiectasia (AT) are rare inherited syndromes characterized by abnormal DNA damage response and caused by pathogenic variants in key DNA repair proteins that are also relevant in the pathogenesis of breast cancer and other cancer types. The risk of cancer in children with these diseases is poorly understood and has never been assessed in a population-based cohort before.

METHODS: We identified 421 patients with FA and 160 patients with AT diagnosed between 1973 and 2020 through German DNA repair disorder reference laboratories. We linked patients' laboratory data with childhood cancer data from the German Childhood Cancer Registry.

RESULTS: Among 421 patients with FA, we observed 33 cases of childhood cancer (15 cases of myelodysplastic syndrome; seven cases of acute myeloid leukemia; two cases of lymphoma, carcinoma, medulloblastoma, and nephroblastoma, respectively; and one case of rhabdomyosarcoma, acute lymphoblastic leukemia, and glioma, respectively) versus 0.74 expected (on the basis of population-based incidence rates in Germany). This corresponds to a 39-fold increased risk (standardized incidence ratio [SIR] = 39; 95% CI, 26 to 56). For all FA subgroups combined, the cancer-specific SIR for myeloid neoplasms was 445 (95% CI, 272 to 687). Among the 160 patients with AT, we observed 19 cases of childhood cancer (15 cases of lymphoma, three cases of leukemia, and one case of medulloblastoma) versus 0.32 expected. This corresponds to a 56-fold increased risk (SIR = 56; 95% CI, 33 to 88). The cancer-specific SIR for Hodgkin lymphoma was 215 (95% CI, 58 to 549) and for non-Hodgkin lymphoma 470 (95% CI, 225 to 865).

CONCLUSION: Approximately 11% of patients with FA and 14% of patients with AT develop cancer by age 18 years.

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