Certain Birth Defects May Raise Risk of Childhood Cancers

child with cancer looking up

There aren't enough data to support the idea that every child with a birth defect should be screened for cancer, says Dr. Walsh.

Children with certain birth defects face a higher risk of developing several pediatric cancers, according to a large epidemiology study presented at the 2018 American Association for Cancer Research (AACR) annual meeting.

The analysis, led by Jeremy Schraw from the Texas Children’s Cancer Center and Baylor College of Medicine, pooled 20 years’ worth of data from four states. It evaluated associations between 60 nonchromosomal birth defects, including certain congenital heart defects, and 31 childhood cancers. (A nonchromosomal birth defect is one in which there is no obvious gain or loss of a chromosome, but could still involve other genetic changes.)

Overall, children with a nonchromosomal birth defect had 2.6 times higher risk of developing any cancer compared with children who had no birth defect.

However, certain birth defects were associated with a higher risk of specific cancers:

  • Ventricular septal defects (a hole in the wall of the heart’s lower chambers) were associated with a tenfold higher risk of hepatoblastoma, a form of liver cancer.
  • Craniosynostosis (fusing of the skull before the brain is fully formed) was associated with a threefold higher risk of neuroblastoma.
  • Right ventricular outflow tract defects (blockage of blood flow in the heart’s lower chamber) were associated with a sevenfold higher risk of neuroblastoma.

Some birth defects, like cleft palate and cleft lip, had no association with any cancer.

Dr. Schraw, the lead author of the study, emphasized in an AACR press release that the retrospective analysis “cannot establish a cause-and-effect relationship between birth defects and childhood cancers” and that he hopes to expand the work.

We spoke with Michael Walsh, an MSK geneticist and pediatric oncologist, to learn more and to put the findings into context.

What is new about this analysis? What are we learning?

I think that it’s an important study. It is a retrospective effort across a huge dataset that provides a better understanding of the overlap between birth defects and childhood cancers.

MSK geneticist and pediatric oncologist Michael Walsh

Michael Walsh

There are a couple syndromes we know about that are associated with cancer. One example is WAGR syndrome, a growth disorder in which children have a number of genes on the 11th chromosome that are deleted or altered. These kids can have features of the syndrome and also an increased risk of cancer. We also know that children with retinoblastoma can have a gene deletion on their 13th chromosome as well as a syndrome that goes along with that. There are also syndromes that aren’t related to the number of chromosomes that include cancer. So this study reinforces what we already know, that there is a spectrum to many syndromes that include increased cancer risk.

Could you put the numbers into context? Is 2.6 times increased risk a large amount?

It’s a small percentage of the overall population but it’s certainly significant because pediatric cancer in general is so rare. Any insight you can gain, even on the smallest group of patients, can provide a much broader understanding. The percentage of children who have these isn’t terribly high, but it’s an important group to learn from.

What’s the key takeaway here? What should people know?

After reading this, someone could think that anyone with a birth defect should be screened for cancer. There aren’t enough data at this point to support that, or to provide any kind of meaningful guidance as to how often that should be done or dictate what the appropriate screening would even be. Those insights will be better understood and more meaningful when specific genes are revealed for the particular associations between birth defects and types of cancer. At this point there’s no standard for how to properly screen without doing any unnecessary harm, like bringing a person in for imaging or blood work that they might not need.

I think that people need to pay attention to which genes are discovered in relation to certain defects. If a gene is leading to a cardiac abnormality and it’s also associated with cellular dysregulation and growth that ultimately leads to cancer, someone with that defect might have screening incorporated into their care. I think this study will provide a group of patients that can be compared to control patients to understand which defects go with which cancer types.

What can doctors and researchers learn from this study? What work needs to be done next?

This study puts numbers to something we observe regularly. Previous research has focused on this topic. So these new data don’t come as a surprise to me because genes have multiple roles.

The next step is to take all the patients with birth defects and a type of cancer and perform genetic sequencing both on the tumors, if they’re available, and the patients’ genetic makeup to see if there are any mutations or changes in transcription factors that play multiple roles.