Christina M Dutzmann1, Claudia Spix2, Isabell Popp3, Melanie Kaiser2, Friederike Erdmann2, Miriam Erlacher4,5,6, Thilo Dörk7, Detlev Schindler3, Reinhard Kalb3, Christian P Kratz1. 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.
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.
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.
Authors: D Schindler; H Seyschab; M Poot; H Hoehn; A Schinzel; J P Fryns; N Tommerup; P S Rabinovitch Journal: Lancet Date: 1987-12-12 Impact factor: 79.321
Authors: Chunling Hu; Steven N Hart; Rohan Gnanaolivu; Hongyan Huang; Kun Y Lee; Jie Na; Chi Gao; Jenna Lilyquist; Siddhartha Yadav; Nicholas J Boddicker; Raed Samara; Josh Klebba; Christine B Ambrosone; Hoda Anton-Culver; Paul Auer; Elisa V Bandera; Leslie Bernstein; Kimberly A Bertrand; Elizabeth S Burnside; Brian D Carter; Heather Eliassen; Susan M Gapstur; Mia Gaudet; Christopher Haiman; James M Hodge; David J Hunter; Eric J Jacobs; Esther M John; Charles Kooperberg; Allison W Kurian; Loic Le Marchand; Sara Lindstroem; Tricia Lindstrom; Huiyan Ma; Susan Neuhausen; Polly A Newcomb; Katie M O'Brien; Janet E Olson; Irene M Ong; Tuya Pal; Julie R Palmer; Alpa V Patel; Sonya Reid; Lynn Rosenberg; Dale P Sandler; Christopher Scott; Rulla Tamimi; Jack A Taylor; Amy Trentham-Dietz; Celine M Vachon; Clarice Weinberg; Song Yao; Argyrios Ziogas; Jeffrey N Weitzel; David E Goldgar; Susan M Domchek; Katherine L Nathanson; Peter Kraft; Eric C Polley; Fergus J Couch Journal: N Engl J Med Date: 2021-01-20 Impact factor: 91.245
Authors: K Savitsky; A Bar-Shira; S Gilad; G Rotman; Y Ziv; L Vanagaite; D A Tagle; S Smith; T Uziel; S Sfez; M Ashkenazi; I Pecker; M Frydman; R Harnik; S R Patanjali; A Simmons; G A Clines; A Sartiel; R A Gatti; L Chessa; O Sanal; M F Lavin; N G Jaspers; A M Taylor; C F Arlett; T Miki; S M Weissman; M Lovett; F S Collins; Y Shiloh Journal: Science Date: 1995-06-23 Impact factor: 47.728
Authors: Carol Durno; Ayse Bahar Ercan; Vanessa Bianchi; Melissa Edwards; Melyssa Aronson; Melissa Galati; Eshetu G Atenafu; Gadi Abebe-Campino; Abeer Al-Battashi; Musa Alharbi; Vahid Fallah Azad; Hagit N Baris; Donald Basel; Raymond Bedgood; Anne Bendel; Shay Ben-Shachar; Deborah T Blumenthal; Maude Blundell; Miriam Bornhorst; Annika Bronsema; Elizabeth Cairney; Sara Rhode; Shani Caspi; Aghiad Chamdin; Stefano Chiaravalli; Shlomi Constantini; Bruce Crooks; Anirban Das; Rina Dvir; Roula Farah; William D Foulkes; Zehavit Frenkel; Bailey Gallinger; Sharon Gardner; David Gass; Mithra Ghalibafian; Catherine Gilpin; Yael Goldberg; Catherine Goudie; Syed Ahmer Hamid; Heather Hampel; Jordan R Hansford; Craig Harlos; Nobuko Hijiya; Saunders Hsu; Junne Kamihara; Rejin Kebudi; Jeffrey Knipstein; Carl Koschmann; Christian Kratz; Valerie Larouche; Alvaro Lassaletta; Scott Lindhorst; Simon C Ling; Michael P Link; Rebecca Loret De Mola; Rebecca Luiten; Michal Lurye; Jamie L Maciaszek; Vanan MagimairajanIssai; Ossama M Maher; Maura Massimino; Rose B McGee; Naureen Mushtaq; Gary Mason; Monica Newmark; Garth Nicholas; Kim E Nichols; Theodore Nicolaides; Enrico Opocher; Michael Osborn; Benjamin Oshrine; Rachel Pearlman; Daniel Pettee; Jan Rapp; Mohsin Rashid; Alyssa Reddy; Lara Reichman; Marc Remke; Gabriel Robbins; Sumita Roy; Magnus Sabel; David Samuel; Isabelle Scheers; Kami Wolfe Schneider; Santanu Sen; Duncan Stearns; David Sumerauer; Carol Swallow; Leslie Taylor; Gregory Thomas; Helen Toledano; Patrick Tomboc; An Van Damme; Ira Winer; Michal Yalon; Lee Yi Yen; Michal Zapotocky; Shayna Zelcer; David S Ziegler; Stefanie Zimmermann; Cynthia Hawkins; David Malkin; Eric Bouffet; Anita Villani; Uri Tabori Journal: J Clin Oncol Date: 2021-05-04 Impact factor: 50.717
Authors: Joseph D Khoury; Eric Solary; Oussama Abla; Yassmine Akkari; Rita Alaggio; Jane F Apperley; Rafael Bejar; Emilio Berti; Lambert Busque; John K C Chan; Weina Chen; Xueyan Chen; Wee-Joo Chng; John K Choi; Isabel Colmenero; Sarah E Coupland; Nicholas C P Cross; Daphne De Jong; M Tarek Elghetany; Emiko Takahashi; Jean-Francois Emile; Judith Ferry; Linda Fogelstrand; Michaela Fontenay; Ulrich Germing; Sumeet Gujral; Torsten Haferlach; Claire Harrison; Jennelle C Hodge; Shimin Hu; Joop H Jansen; Rashmi Kanagal-Shamanna; Hagop M Kantarjian; Christian P Kratz; Xiao-Qiu Li; Megan S Lim; Keith Loeb; Sanam Loghavi; Andrea Marcogliese; Soheil Meshinchi; Phillip Michaels; Kikkeri N Naresh; Yasodha Natkunam; Reza Nejati; German Ott; Eric Padron; Keyur P Patel; Nikhil Patkar; Jennifer Picarsic; Uwe Platzbecker; Irene Roberts; Anna Schuh; William Sewell; Reiner Siebert; Prashant Tembhare; Jeffrey Tyner; Srdan Verstovsek; Wei Wang; Brent Wood; Wenbin Xiao; Cecilia Yeung; Andreas Hochhaus Journal: Leukemia Date: 2022-06-22 Impact factor: 12.883