title: Cancer risks in children with congenital malformations in the nervous and circulatory system-A population based cohort study.
abstract: OBJECTIVE
  We estimated the age and organ-specific cancer risk for children with a congenital malformation (CM) in the nervous or in the circulatory system.
  
  
  METHODS
  We identified 1,709,456 live born singletons in Denmark between 1 January 1977 and 31 December 2007 and excluded children with chromosomal birth defects. Information on CMs was obtained from the Danish National Hospital Register. Information on cancer occurrence was obtained from the Danish Cancer Registry. We applied Cox proportional hazards regression model to estimate hazard ratios (HR) for cancer. Children entered into the CM cohort on the day of birth regardless of when the CM was diagnosed or on the day of CM diagnosis in an alternative analysis.
  
  
  RESULTS
  Overall, 4484 (0.26%) and 24,643 (1.44%) children were diagnosed with a CM in the nervous and in the circulatory system, respectively. Compared with children without any CM, children with a CM in the nervous system had a 5.97 fold (95%CI [confidence interval]: 4.66-7.64) higher risk of cancer, including cancer in the central nervous system (HR=18.84, 95%CI: 12.67-28.01), in the mesothelial and soft tissue (HR=15.64, 95%CI: 7.99-30.60), in the skin (HR=4.91, 95%CI: 2.19-11.0). The associations were stronger early in life. Children with a CM in the circulatory system had a 2.64 fold (95%CI: 2.21-3.16) higher risk of cancer, including cancer in the lymphatic and haematopoietic tissues (HR=3.22, 95%CI: 2.43-4.27) and cancer in the CNS (HR=2.40, 95%CI: 1.43-4.02). Some of these associations were weaker in the alternative analysis. Children with subtypes of CM in the two systems showed a higher cancer risk.
  
  
  CONCLUSIONS
  Children who were diagnosed with a CM in the nervous system had a substantially higher cancer risk especially early in life. Children diagnosed with a CM in the circulatory system had a moderately higher cancer risk.
authors.affiliation: Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus 8000, Denmark. Electronic address: ys@soci.au.dk.
authors.forename: Yuelian
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus 8000, Denmark.
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.affiliation: Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus 8000, Denmark; Department of Epidemiology, School of Public Health, University of California at Los Angeles, Los Angeles, CA, USA.
authors.forename: Jørn
authors.initials: J
authors.lastname: Olsen
mesh_terms: D000293:Adolescent; D018376:Cardiovascular Abnormalities / Q000150:complications*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009369:Neoplasms / Q000453:epidemiology*; D009421:Nervous System Malformations / Q000150:complications*; D016016:Proportional Hazards Models; D012042:Registries; D012306:Risk; D055815:Young Adult
keywords: Circulatory system; Cohort; Congenital abnormalities; Epidemiology; Neoplasms; Nervous system