With Philip J. Lupo, PhD, of Baylor College of Medicine and Texas Children' Cancer & Hematology Centers
Some birth defects—like trisomy 21 and WAGR syndrome—are known to be linked to increased risk of childhood cancers. But there are still several questions about the link between other birth defects and childhood cancer risk, including associations between childhood cancers and non-chromosomal birth defects.
A new study looked at an unprecedented number of births to shed some light on some of these unknowns. Researchers analyzed registry data that included 10 million children in four different states, comparing associations between identified birth defects and childhood cancers. The researchers looked at 40 specific birth defect-childhood cancer associations. The study was published online ahead of print in JAMA Oncology (doi:10.1001/jamaoncol.2019.1215).
The data replicates some previously known associations between chromosomal birth defects and childhood cancers, and also reveals some previously unknown associations between non-chromosomal birth defects and childhood cancers.
The research points to several new avenues for research to better understand these links, including understanding the genomic pathways that might underlie the overlap of these conditions, evaluating how early-life exposures may predispose children with certain birth defects to cancer, and assessing treatment outcomes in children with birth defects who are diagnosed with cancer, explained lead study author Philip J. Lupo, PhD, Associate Professor of Pediatrics at Baylor College of Medicine and Co-Director of the Epidemiology Program at Texas Children's Cancer and Hematology Centers.
In an interview with Oncology Times, Lupo shared his thoughts about the new findings.
1. Some birth defects have previously been linked to cancer risk. What's new about these findings?
"We do know that certain birth defects are associated with cancer risk. However, less is known about those birth defects that we often call 'non-chromosomal,' which often have no known genetic cause. Most birth defects fall into this category, so we felt it was important to characterize cancer risk for these children.
"Additionally, it was not clear from previous studies what cancers were most strongly associated with non-chromosomal birth defects. We did identify several novel birth defect-pediatric cancer associations, including craniosynostosis and hepatoblastoma; pyloric stenosis and medulloblastoma; and several different congenital heart defects and neuroblastoma. Additionally, the cancers most frequently associated with non-chromosomal defects were hepatoblastoma and neuroblastoma. We think this information could lead to new insights into the genes and environmental exposures that lead both to birth defects and pediatric cancer.
"A key finding is that certain non-chromosomal birth defects (especially having multiple birth defects) are strongly associated with cancer. However, as cancer in children is very rare, for most children this will not be the case."
2. This dataset includes more than 10 million individuals, which is a huge number. Does that large number make the findings conclusive?
"While there have been some very well-designed studies evaluating the relationship between birth defects and cancer, few have been large enough to evaluate the associations between specific birth defects and specific pediatric cancers. Because several members of our research team are involved both in birth defects and cancer surveillance across multiple states, we knew we could pool our resources and link these registries to conduct one of the largest studies to more fully explore this research question.
"An important aspect of this study was the ability to link population-based disease registries—specifically birth defects and cancer registries. We think there are some conclusive findings, like the overall association between non-chromosomal birth defects and pediatric cancer. However, several of our specific findings need to be replicated in independent studies."
3. What are the implications of these findings that cancer care providers need to know now?
"In terms of future research, I think there are several implications. First, it will be critical to evaluate the mechanisms underlying these associations. We are hoping to do this through genetic studies. Second, it will be important to see how children with birth defects differ in terms of treatment outcomes after being diagnosed with cancer. This could inform treatment strategies. However, it is currently too soon to make recommendations for treatment based on our findings.
"The clinical implications of this research for children with birth defects are limited at present, as most children with birth defects will not develop cancer (the absolute risk was far below 1%). If genes that explain this risk are identified in the future, that could trigger genetic testing for a subset of children with birth defects. However, it is too soon to make specific recommendations at this time."