title: Confounding of the Association between Radiation Exposure from CT Scans and Risk of Leukemia and Brain Tumors by Cancer Susceptibility Syndromes.
abstract: BACKGROUND
  Recent studies linking radiation exposure from pediatric computed tomography (CT) to increased risks of leukemia and brain tumors lacked data to control for cancer susceptibility syndromes (CSS). These syndromes might be confounders because they are associated with an increased cancer risk and may increase the likelihood of CT scans performed in children.
  
  
  METHODS
  We identify CSS predisposing to leukemia and brain tumors through a systematic literature search and summarize prevalence and risk estimates. Because there is virtually no empirical evidence in published literature on patterns of CT use for most types of CSS, we estimate confounding bias of relative risks (RR) for categories of radiation exposure based on expert opinion about the current and previous patterns of CT scans among CSS patients.
  
  
  RESULTS
  We estimate that radiation-related RRs for leukemia are not meaningfully confounded by Down syndrome, Noonan syndrome, or other CSS. In contrast, RRs for brain tumors may be overestimated due to confounding by tuberous sclerosis complex (TSC) while von Hippel-Lindau disease, neurofibromatosis type 1, or other CSS do not meaningfully confound. Empirical data on the use of CT scans among CSS patients are urgently needed.
  
  
  CONCLUSIONS
  Our assessment indicates that associations with leukemia reported in previous studies are unlikely to be substantially confounded by unmeasured CSS, whereas brain tumor risks might have been overestimated due to confounding by TSC.
  
  
  CONCLUSIONS
  Future studies should identify TSC patients in order to avoid overestimation of brain tumor risks due to radiation exposure from CT scans.
authors.affiliation: Department of Epidemiology and Biostatistics, Netherlands Cancer Institute, Amsterdam, the Netherlands.
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Meulepas
authors.affiliation: Department of Paediatric Oncology, Emma Children's Hospital, Academic Medical Center Amsterdam, the Netherlands.
authors.forename: Cécile M
authors.initials: CM
authors.lastname: Ronckers
authors.affiliation: Department of Paediatric Oncology, Emma Children's Hospital, Academic Medical Center Amsterdam, the Netherlands.
authors.forename: Johannes
authors.initials: J
authors.lastname: Merks
authors.affiliation: Department of Paediatrics, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Michel E
authors.initials: ME
authors.lastname: Weijerman
authors.affiliation: National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland.
authors.forename: Jay H
authors.initials: JH
authors.lastname: Lubin
authors.affiliation: Department of Epidemiology and Biostatistics, Netherlands Cancer Institute, Amsterdam, the Netherlands. m.hauptmann@nki.nl.
authors.forename: Michael
authors.initials: M
authors.lastname: Hauptmann
mesh_terms: D001932:Brain Neoplasms / Q000453:epidemiology* / Q000209:etiology* / Q000473:pathology; D002648:Child; D004198:Disease Susceptibility; D006801:Humans; D007938:Leukemia / Q000453:epidemiology* / Q000209:etiology* / Q000473:pathology; D015201:Meta-Analysis as Topic; D009367:Neoplasm Staging; D009381:Neoplasms, Radiation-Induced / Q000453:epidemiology* / Q000473:pathology; D015995:Prevalence; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors; D013577:Syndrome; D014057:Tomography, X-Ray Computed / Q000009:adverse effects*; D014481:United States / Q000453:epidemiology