Nonchromosomal Birth Defects Linked With Childhood Cancers

Alexander M. Castellino, PhD

April 16, 2018

CHICAGO — In a retrospective analysis of registry data on more than 10 million live births, the risk for childhood cancers was 2.6-fold higher in children born with nonchromosomal abnormalities than in children born without any defects. In addition, some cancers were linked with specific birth defects.

These data were reported at the American Association for Cancer Research (AACR) 2018 Annual Meeting.

At a press conference, presenter Jeremy M. Schraw, PhD, explained that approximately 1 in 33 children are born with a birth defect and there are data linking chromosomal abnormalities in Down's syndrome with increased cancer risk. In addition, he said that data linking the majority of birth defects to childhood cancers are growing. 

"We are trying to learn more about this connection so that we can potentially identify children who may benefit from early cancer detection," Schraw said.

Schraw is a postdoctoral fellow at Texas Children's Cancer Center, Texas Children's Hospital, and Department of Medicine, Section of Epidemiology and Population Science, Baylor College of Medicine, Houston.

Study Details

In this study, Schraw and his colleagues pooled statewide registry data from Texas, Michigan, North Carolina, and Arkansas for 1992 to 2013. Information from birth certificates, birth defects registries, and cancer registries were linked, and in a statistical model they evaluated associations between 60 birth defects and 31 childhood cancers.

The registries provided the researchers with more than 10 million births; of these, 517,548 children were identified as having nonchromosomal birth defects and 14,774 as having developed cancer.

With a hazard ratio (HR) of 2.6, the risk for any cancer significantly increased in children with nonchromosomal birth defects compared with children who did not have any birth defect.

Some birth defects, including the fairly common cleft palate and cleft lip, had no association with childhood cancer, Schraw pointed out.

But some cancers were strongly linked with specific birth defects. For example, risk for hepatoblastoma was 10.5-fold higher in children with ventricular septal defects and 10-fold higher in children with craniosynostosis. Risk for both astrocytoma and ependymoma was about  10-  to 20-fold higher in children with central nervous system defects.

"The limitation of the study is that is cannot establish a cause-and-effect relationship between birth defects and childhood cancers and there is no data on time period between birth and cancer diagnosis," Schraw said. "It is too soon to make recommendations based on this information," he noted.

Moderating the press conference, Louis M. Weiner, MD, co-chair of the AACR Annual Meeting Clinical Trials Committee and director of the Georgetown Lombardi Comprehensive Cancer Center, Washington, DC, acknowledged that this was an enormous observational study that showed about a 2.5-fold increase in childhood cancers in children with nongenetic birth defects.

He asked how this finding can be validated and "at what point do we feel comfortable making screening recommendations?"

Schraw responded that the rarity of pediatric cancers makes it difficult to validate these observations prospectively. "Childhood cancer is rare and, therefore, the risk that a child with a nonchromosomal birth defect will develop cancer during childhood is low. However, a similar study across an independent registry database may be able to corroborate these findings," he noted. "A case-control study may also be practical," he suggested.

"However, it is too soon for making clinical recommendations," Schraw said. In an AACR news statement he said, "We do hope our findings spur additional inquiries into these associations, so that we may better understand the biology underlying these associations."

This study was supported by the Cancer Prevention Research Institute of Texas and Alex's Lemonade Stand Foundation.

American Association for Cancer Research (AACR) 2018 Annual Meeting. Abstract LB-161. Presented April 15, 2018.

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