Study reveals elevated cancer risk in children with birth defects

June 25, 2019

Childhood cancer is a rare occurrence in the overall population but may be somewhat more frequent in children born with birth defects. To better understand the link between cancer risk and birth defects, a collaborative team of scientists led by Baylor College of Medicine has assembled the largest study to date to evaluate cancer risk in children with birth defects. The study appears in JAMA Oncology.

"While cancer risk in children with certain chromosomal defects like Down syndrome is well established, much less is known for children with birth defects where there is no known genetic cause, sometimes called non-chromosomal defects," said Dr. Philip Lupo, associate professor of pediatrics - hematology oncology and member of the Dan L Duncan Comprehensive Cancer Center at Baylor. "Non-chromosomal defects, as a group, affect more children, but one of the primary challenges of understanding risk among these children is that limited sample sizes make studying specific defects, like spina bifida, more difficult."

The research team gathered data from birth, birth defect and cancer registries across Texas, Arkansas, Michigan and North Carolina to generate a birth cohort of more than 10 million children born between 1992 and 2013. The investigators looked at diagnoses of cancer until 18 years of age to determine differences in cancer risk between those with and without birth defects.

Researchers found that, compared to children without any birth defect, children with chromosomal defects were almost 12 times more likely to develop cancer, while children with non-chromosomal defects were 2.5 times more likely to develop cancer. Additionally, children with more than one non-chromosomal defect had a corresponding increase in cancer risk.

"Our two key objectives in this study were 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, and to uncover clues as to why cancer occurs more frequently in this population," said Dr. Jeremy Schraw, postdoctoral associate in the Section of Epidemiology and Population Sciences at Baylor. "These findings solidify our understanding of cancer risk in these children and show that we need additional research in this area."

Cancer types that were more frequent in children with non-chromosomal defects included hepatoblastoma and neuroblastoma.

While these findings identify specific, strong associations between birth defects and cancer, Schraw said that it is important to remember that both birth defects and cancer are still rare occurrences.

"This study is important in that it is the largest and most informative of its kind. The large sample size allowed us to evaluate cancer risk in children with both chromosomal versus non-chromosomal defects and revealed links between specific cancers and specific birth defects. These data can also help us to study and understand differences in outcomes down the road for children with cancer," said Dr. Sharon Plon, professor of pediatrics - oncology and molecular and human genetics and co-director of the Pediatric Cancer Program in the Dan L Duncan Comprehensive Cancer Center at Baylor.

"In the future, we hope to identify the specific genes behind these associations and systematically research what happens from the time of birth to the time of cancer onset to also understand if environmental factors may be contributing to cancer development," Lupo said. "This study provides new understanding about biology and the mechanisms that may lead to these complex outcomes in this population."
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This study was supported by the Cancer Prevention and Research Institute of Texas, Alex's Lemonade Stand Foundation, the National Cancer Institute, and Arkansas Biosciences Institute. For a full list of contributors, visit the journal website.

Baylor College of Medicine

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