Pediatric cancer incidence among individuals with overgrowth syndromes and overgrowth features: A population‐based assessment in seven million children

• Published in: Cancer 2024-02, Vol.130 (3), p.467-475
• Main Authors: Connolly, Gillean K., Harris, Rachel D., Shumate, Charles, Rednam, Surya P., Canfield, Mark A., Plon, Sharon E., Nguyen, Joanne, Schraw, Jeremy M., Lupo, Philip J.
• Format: Article
• Language: English
• Subjects: Beckwith-Wiedemann syndrome; Birth defects; Cancer; Children; Confidence intervals; congenital abnormalities; Congenital defects; Disorders; epidemiology; genetic predisposition to disease; Health risks; neoplasms; Pediatrics; Population studies; Regression analysis; Regression models; Risk; Statistical analysis
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.35041

Background Overgrowth syndromes (e.g., Beckwith–Wiedemann) are associated with an increased risk of pediatric cancer, although there are few population‐based estimates of risk. There are also limited studies describing associations between other overgrowth features (e.g., hepatosplenomegaly) and pediatric cancer. Therefore, cancer risk among children with these conditions was evaluated with data from a large, diverse population‐based registry linkage study. Methods This study includes all live births in Texas during the years 1999–2017. Children with overgrowth features and syndromes were identified from the Texas Birth Defects Registry; children with cancer were identified by linkage to the Texas Cancer Registry. Cox regression models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the association between each overgrowth syndrome/feature and cancer, which were adjusted for infant sex and maternal age. Results In the total birth cohort (n = 6,997,422), 21,207 children were identified as having an overgrowth syndrome or feature. Children with Beckwith–Wiedemann syndrome were 42 times more likely to develop pediatric cancer (95% CI, 24.20–71.83), with hepatoblastoma being the most common, followed by Wilms tumor. The presence of any isolated overgrowth feature was associated with increased cancer risk (HR, 4.70; 95% CI, 3.83–5.77); associations were strongest for hepatosplenomegaly (HR, 23.04; 95% CI, 13.37–39.69) and macroglossia (HR, 11.18; 95% CI, 6.35–19.70). Conclusions This population‐based assessment confirmed prior findings that children with either overgrowth syndromes or features were significantly more likely to develop cancer. Overall, this study supports recommendations for cancer surveillance in children with these conditions and may also inform future research into cancer etiology. Children with either overgrowth syndromes or features are at a significantly increased risk for childhood cancer. Results from this study may ultimately be used to guide recommendations for cancer surveillance in children with overgrowth syndromes/features and may also inform future research into cancer etiology.