Cancer diagnostic profile in children with structural birth defects: An assessment in 15,000 childhood cancer cases

Cancer. 2020 Aug 1;126(15):3483-3492. doi: 10.1002/cncr.32982. Epub 2020 May 29.


Background: Birth defects are established risk factors for childhood cancer. Nonetheless, cancer epidemiology in children with birth defects is not well characterized.

Methods: Using data from population-based registries in 4 US states, this study compared children with cancer but no birth defects (n = 13,111) with children with cancer and 1 or more nonsyndromic birth defects (n = 1616). The objective was to evaluate cancer diagnostic characteristics, including tumor type, age at diagnosis, and stage at diagnosis.

Results: Compared with the general population of children with cancer, children with birth defects were diagnosed with more embryonal tumors (26.6% vs 18.7%; q < 0.001), including neuroblastoma (12.5% vs 8.2%; q < 0.001) and hepatoblastoma (5.0% vs 1.3%; q < 0.001), but fewer hematologic malignancies, including acute lymphoblastic leukemia (12.4% vs 24.4%; q < 0.001). In age-stratified analyses, differences in tumor type were evident among children younger than 1 year and children 1 to 4 years old, but they were attenuated among children 5 years of age or older. The age at diagnosis was younger in children with birth defects for most cancers, including leukemia, lymphoma, astrocytoma, medulloblastoma, ependymoma, embryonal tumors, and germ cell tumors (all q < 0.05).

Conclusions: The results indicate possible etiologic heterogeneity in children with birth defects, have implications for future surveillance efforts, and raise the possibility of differential cancer ascertainment in children with birth defects.

Lay summary: Scientific studies suggest that children with birth defects are at increased risk for cancer. However, these studies have not been able to determine whether important tumor characteristics, such as the type of tumor diagnosed, the age at which the tumor is diagnosed, and the degree to which the tumor has spread at the time of diagnosis, are different for children with birth defects and children without birth defects. This study attempts to answer these important questions. By doing so, it may help scientists and physicians to understand the causes of cancer in children with birth defects and diagnose cancer at earlier stages when it is more treatable.

Keywords: birth defects; cancer predisposition; childhood cancer; epidemiology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Congenital Abnormalities / diagnosis*
  • Congenital Abnormalities / epidemiology
  • Congenital Abnormalities / pathology
  • Female
  • Hematologic Neoplasms / complications
  • Hematologic Neoplasms / diagnosis
  • Hematologic Neoplasms / epidemiology
  • Hematologic Neoplasms / pathology
  • Hepatoblastoma / complications
  • Hepatoblastoma / diagnosis
  • Hepatoblastoma / epidemiology
  • Hepatoblastoma / pathology
  • Humans
  • Infant
  • Infant, Newborn
  • Liver Neoplasms / complications
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / epidemiology
  • Liver Neoplasms / pathology
  • Male
  • Neoplasms / complications
  • Neoplasms / diagnosis*
  • Neoplasms / epidemiology*
  • Neoplasms / pathology
  • Neuroblastoma / complications
  • Neuroblastoma / diagnosis
  • Neuroblastoma / epidemiology
  • Neuroblastoma / pathology
  • Registries
  • Risk Factors
  • United States / epidemiology