Study finds increased risk of certain cancers among children and adolescents with birth defects

A multi-institutional study led by Dr. Philip Lupo, co-director of the Childhood Cancer Epidemiology and Prevention Program at Texas Children's Cancer and Hematology Center and associate professor at Baylor College of Medicine, finds children and adolescents with specific birth defects are at an increased risk of developing certain cancers. Dr. Sharon Plon, a leading medical geneticist who co-directs the Cancer Genetics and Genomics Program in the Texas Children’s Cancer and Hematology Center and a professor at Baylor College of Medicine and Dr. Jeremy Schraw, a post-doctoral fellow at Baylor College of Medicine were other key investigators involved in this study.

The study, published in JAMA Oncology, is the largest population-based assessment of cancer risk among children with birth defects to date and reports strong associations between 40 specific birth defects and childhood cancers, several of which are novel. Moreover, they found an increased risk of cancer in children with multiple major non-chromosomal birth defects. One of the key objectives of this study was to identify children who are at an increased risk for cancer because subsets of these children may one day benefit from screening and better clinical management. Moreover, findings from this study provide scientists with new insights that will be starting point to uncover the mechanistic link between specific birth defects and childhood cancers. 

Globally, more than 250,000 children are diagnosed with cancer annually, and in the United States, cancer remains the leading cause of death by disease among children and adolescents. Being born with a chromosomal birth defect is one of the strongest known risk factors for childhood cancers. For example, children with trisomy 21 have a 20-fold increased risk of developing acute lymphoblastic leukemia (ALL).

On the other hand, non-chromosomal defects, as a group, affect more children. However, it had been difficult to conclusively establish a link between certain rare and/or non-chromosomal birth defects (e.g., craniosynostosis) and specific cancer subtypes (e.g., hepatoblastoma), due to the lack of a reasonable number of eligible patients in previous assessments. Moreover, a growing number of studies have suggested a link between the number of birth defects and an increased risk for cancer. In the absence of a sufficient number of patients, these and other such associations could not be clearly established.

To address this issue, for this study, researchers established a diverse and large population-based cohort by pooling statewide registry data on births, birth defects, and cancer from Texas, Arkansas, Michigan and North Carolina. The study included more than 10 million children who were born between 1992 and 2013 in these states. The researchers monitored these children up to 18 years of age for a cancer diagnosis and performed rigorous statistical analyses to explore trends and potential novel associations.

They found, compared to children without any birth defect, children with chromosomal anomalies were roughly 11-times more likely to develop cancer, whereas children with non-chromosomal defects were twice as likely to develop cancer. Children with two or more major birth defects had markedly greater risks than children with fewer or no birth defects. For instance, children with four or more major birth defects were five-times more likely to develop cancer than children without a birth defect.

In general, hepatoblastoma and neuroblastoma were among the most frequently occurring cancer types in children with non-chromosomal defects. With this approach, researchers uncovered novel associations between specific non-chromosomal birth defects and childhood cancers, such as craniosynostosis and hepatoblastoma, pyloric stenosis and medulloblastoma, as well as the presence of several congenital cardiac defects and neuroblastoma. Notably, some tumors, including germ cell tumors, were strongly associated with defects in multiple different organ systems whereas some cancers, such as ALL were associated with only a few categories of birth defects and yet others such as bone tumors were not strongly associated with birth defects.

Researchers are hopeful these findings may inform establishment of new guidelines for regular surveillance and screening for particular types of cancers in children with specific birth defects. Early cancer detection and diagnosis could lead to better outcomes for these children and teenagers, who may be already dealing with several severe health issues and disabilities.

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