Emily C Marlow1, Jonathan Ducore2, Marilyn L Kwan3, Stephanie Y Cheng4, Erin J A Bowles5, Robert T Greenlee6, Jason D Pole7, Alanna Kulchak Rahm8, Natasha K Stout9, Sheila Weinmann10, Rebecca Smith-Bindman11, Diana L Miglioretti12. 1. Graduate Group in Epidemiology, University of California, Davis, Davis, CA; Department of Public Health Sciences, University of California, Davis, Davis, CA. 2. Department of Pediatrics, University of California, Davis, Davis, CA. 3. Division of Research, Kaiser Permanente Northern California, Oakland, CA. 4. ICES, Toronto, Ontario, Canada. 5. Kaiser Permanente Washington Health Research Institute, Kaiser Permanente Washington, Salt Lake City, UT. 6. Marshfield Clinic Research Institute, Marshfield Clinic Health System, Marshfield, WI. 7. ICES, Toronto, Ontario, Canada; Centre for Health Service Research, University of Queensland, Brisbane, Australia; Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada. 8. Genomic Medicine Institute, Geisinger, Forty Fort, PA. 9. Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA. 10. Center for Health Research, Kaiser Permanente Northwest, Portland, OR; Center for Integrated Health Care Research, Kaiser Permanente Hawaii, Honolulu, HI. 11. Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA; Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA; Department of Obstetrics, Gynecology and Reproductive Medicine, University of California, San Francisco, San Francisco, CA; Philip R. Lee Institute for Health Policy Studies, University of California, San Francisco, San Francisco, CA. 12. Department of Public Health Sciences, University of California, Davis, Davis, CA; Kaiser Permanente Washington Health Research Institute, Kaiser Permanente Washington, Salt Lake City, UT. Electronic address: dmiglioretti@ucdavis.edu.
Abstract
OBJECTIVE: To assess leukemia risks among children with Down syndrome in a large, contemporary cohort. STUDY DESIGN: Retrospective cohort study including 3 905 399 children born 1996-2016 in 7 US healthcare systems or Ontario, Canada, and followed from birth to cancer diagnosis, death, age 15 years, disenrollment, or December 30, 2016. Down syndrome was identified using International Classification of Diseases, Ninth and Tenth Revisions, diagnosis codes. Cancer diagnoses were identified through linkages to tumor registries. Incidence and hazard ratios (HRs) of leukemia were estimated for children with Down syndrome and other children adjusting for health system, child's age at diagnosis, birth year, and sex. RESULTS: Leukemia was diagnosed in 124 of 4401 children with Down syndrome and 1941 of 3 900 998 other children. In children with Down syndrome, the cumulative incidence of acute myeloid leukemia (AML) was 1405/100 000 (95% CI 1076-1806) at age 4 years and unchanged at age 14 years. The cumulative incidence of acute lymphoid leukemia in children with Down syndrome was 1059/100 000 (95% CI 755-1451) at age 4 and 1714/100 000 (95% CI 1264-2276) at age 14 years. Children with Down syndrome had a greater risk of AML before age 5 years than other children (HR 399, 95% CI 281-566). Largest HRs were for megakaryoblastic leukemia before age 5 years (HR 1500, 95% CI 555-4070). Children with Down syndrome had a greater risk of acute lymphoid leukemia than other children regardless of age (<5 years: HR 28, 95% CI 20-40, ≥5 years HR 21, 95% CI 12-38). CONCLUSIONS: Down syndrome remains a strong risk factor for childhood leukemia, and associations with AML are stronger than previously reported.
OBJECTIVE: To assess leukemia risks among children with Down syndrome in a large, contemporary cohort. STUDY DESIGN: Retrospective cohort study including 3 905 399 children born 1996-2016 in 7 US healthcare systems or Ontario, Canada, and followed from birth to cancer diagnosis, death, age 15 years, disenrollment, or December 30, 2016. Down syndrome was identified using International Classification of Diseases, Ninth and Tenth Revisions, diagnosis codes. Cancer diagnoses were identified through linkages to tumor registries. Incidence and hazard ratios (HRs) of leukemia were estimated for children with Down syndrome and other children adjusting for health system, child's age at diagnosis, birth year, and sex. RESULTS: Leukemia was diagnosed in 124 of 4401 children with Down syndrome and 1941 of 3 900 998 other children. In children with Down syndrome, the cumulative incidence of acute myeloid leukemia (AML) was 1405/100 000 (95% CI 1076-1806) at age 4 years and unchanged at age 14 years. The cumulative incidence of acute lymphoid leukemia in children with Down syndrome was 1059/100 000 (95% CI 755-1451) at age 4 and 1714/100 000 (95% CI 1264-2276) at age 14 years. Children with Down syndrome had a greater risk of AML before age 5 years than other children (HR 399, 95% CI 281-566). Largest HRs were for megakaryoblastic leukemia before age 5 years (HR 1500, 95% CI 555-4070). Children with Down syndrome had a greater risk of acute lymphoid leukemia than other children regardless of age (<5 years: HR 28, 95% CI 20-40, ≥5 years HR 21, 95% CI 12-38). CONCLUSIONS: Down syndrome remains a strong risk factor for childhood leukemia, and associations with AML are stronger than previously reported.
Authors: Eleni Th Petridou; Marios K Georgakis; Friederike Erdmann; Xiaomei Ma; Julia E Heck; Anssi Auvinen; Beth A Mueller; Logan G Spector; Eve Roman; Catherine Metayer; Corrado Magnani; Maria S Pombo-de-Oliveira; Sameera Ezzat; Michael E Scheurer; Ana Maria Mora; John D Dockerty; Johnni Hansen; Alice Y Kang; Rong Wang; David R Doody; Eleanor Kane; Waffa M Rashed; Nick Dessypris; Joachim Schüz; Claire Infante-Rivard; Alkistis Skalkidou Journal: Eur J Epidemiol Date: 2018-05-14 Impact factor: 8.082
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Authors: Amy Berrington de Gonzalez; Jane A Salotti; Kieran McHugh; Mark P Little; Richard W Harbron; Choonsik Lee; Estelle Ntowe; Melissa Z Braganza; Louise Parker; Preetha Rajaraman; Charles Stiller; Douglas R Stewart; Alan W Craft; Mark S Pearce Journal: Br J Cancer Date: 2016-02-16 Impact factor: 7.640
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