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

Abstract

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.

Cancer Risk by Attained Age among Children with Birth Defects in Arkansas

“…In another recent paper, authors investigated stage at cancer diagnosis by birth defects status and did not observe earlier diagnoses of cancer among children with birth defects. 36 Based on these findings, we propose that differential diagnostic scrutiny or disease surveillance does not substantially impact our findings.…”

Unraveling the Genetic Architecture of Hepatoblastoma Risk: Birth Defects and Increased Burden of Germline Damaging Variants in Gastrointestinal/Renal Cancer Predisposition and DNA Repair Genes

“…HB are reported to occur in association with a wide variety of congenital abnormalities ( Narod et al, 1997 ; Ansell et al, 2005 ; Scollon et al, 2017 ), especially craniosynostosis and renal anomalies ( de Camargo et al, 2011 ), which we also observed in this study. Two recent studies used large population-based linkage data to investigate the association between birth defects and childhood cancer, showing that HB are more prevalent in children with birth defects (5.0% in this group compared to 1.3% in children with cancer; Schraw et al, 2020 ) and frequently occurs in association with craniosynostosis ( Lupo et al, 2019 ). It is interesting that we found in this group of patients a marginally significant result suggesting a tendency of high-risk tumors to develop in patients who also have craniofacial defects.…”

Hepatoblastoma

“…Still, an explanation for this observation -accidental or causal connection -could not be established (8). The fact that relatively common conditions such as pre-eclampsia, fetal distress before or during childbirth, or congenital malformations could play roles as possible tumor inducers could allegedly be statistically determined in some studies, but an explanation for these observations is still missing (9). Regardless of these observations, over the last few decades, various genetic diseases have been found to be risk factors for developing hepatoblastoma.…”