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A Population-Based Assessment of Cancer Risk in Children With VACTERL.

Ji Yun Tark1, Alexander Renwick1,2, Giorgio Tettamanti3,4

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American Journal of Medical Genetics. Part A
|December 23, 2025
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Summary

Children with VACTERL (vertebral, anal, cardiac, tracheoesophageal, renal, limb defects) have a significantly higher risk of developing childhood cancer, especially embryonal tumors. This finding suggests shared developmental pathways may link these conditions.

Keywords:
Fanconi anemiaVACTERLVATERbirth defectscancermultiple congenital anomaliesoncologypediatrics

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Area of Science:

  • Pediatric Oncology
  • Developmental Biology
  • Epidemiology

Background:

  • VACTERL (vertebral, anal, cardiac, tracheoesophageal fistula, renal, and limb defects) is a nonrandom association of birth anomalies.
  • The association between VACTERL and childhood cancer risk is not well understood.

Purpose of the Study:

  • To evaluate the cancer risk in children diagnosed with VACTERL using a population-based study.
  • To compare cancer incidence in children with VACTERL to unaffected children.

Main Methods:

  • Analysis of data from the US-based Genetic Overlap Between Anomalies and Cancer in Kids (GOBACK) Study.
  • VACTERL defined as ≥3 associated defects; Cox regression and Kaplan-Meier analyses used.
  • Comparison of cancer risk (before age 18) between VACTERL cases and controls.

Main Results:

  • Of 21,224,742 births, 2288 met VACTERL criteria; 8 developed cancer.
  • Children with VACTERL showed a 3.0-fold increased cancer risk (HR=3.0, 95% CI: 1.5-6.0).
  • Embryonal tumors were particularly elevated (HR=6.9, 95% CI: 2.9-16.5) in VACTERL patients.

Conclusions:

  • VACTERL is associated with a significantly increased risk of childhood cancer.
  • Shared developmental or epigenetic factors may contribute to both VACTERL and cancer.
  • Further research is needed to identify VACTERL subgroups for targeted cancer surveillance.