We discussed some findings from the GOBACK study which is an acronym for Genetic Overlap Between Anomalies and Cancer in Kids. This is a study which we’ve conducted that has two components and the results that I’m sharing here at the meeting pertain to the association analysis. In that portion of the study what we did is we pooled data from birth defects and cancer registries in Texas, Arkansas, Michigan and North Carolina over a period of about fifteen years on average, depending on the state, to look at specific associations between non-chromosomal birth defects and childhood cancers in the general population.
What is a chromosomal birth defect?
Chromosomal birth defects refer to conditions where there’s either addition or deletion of an entire chromosome or an arm of a chromosome. Probably the best known example would be Down’s Syndrome or trisomy 21. Trisomies occur in a number of other chromosomes, for example trisomy 13 and 18 are recognised clinical entities. The majority of birth defects that occur, about 85% or so, are so-called non-syndromic or non-chromosomal birth defects and these are just structural birth defects which are found in the absence of a known chromosome or genetic cause.
What did your study find?
It was a very large study so between the four states and over the time period that we collected data we were able to get information on about 10.1 million live births. Because of the sample size that’s needed to look at these specific cancer birth defect associations previous data are limited in that they had to group people either who had somewhat related cancers or somewhat related birth defects when considering risk. But because of our sample size we were able to look much more specifically at individual birth defects and connection with individual cancers.
So we found associations between a number of specific non-chromosomal birth defects and childhood cancers, notably several forms of congenital heart disease, for example ventricular septal defects and ventricular outflow tract defects in either the right or left ventricle were both associated with childhood cancers. Those were most frequently associated with either neuroblastoma or hepatoblastoma and depending on the defect and the cancer that we’re discussing those children were at between seven and twenty times the risk of those particular cancers compared to a child without a birth defect. There are also a number of interesting associations either between craniofacial or central nervous system birth defects, generally with central nervous system tumours but not exclusively.
What can we do now that we know there are clear correlations?
The key finding from this study is that when you look at these specific associations we see that in some cases these children are at pretty remarkably increased risk of cancer. So some of the next steps that we envision for the study will be sequencing, informative families, where a child is affected by both a birth defect and a cancer to look for possible genetic causes of cancer in children with birth defects. We’ll have to use other datasets to do it but we’re also very interested in investigating possible roles for treatment-related exposures. So children who have congenital heart disease, for example, may undergo a number of diagnostic procedures to have that defect diagnosed and repaired and it could be possible that that contributes to their cancer risk. So we’re going to try to investigate some of the mechanisms that we believe are behind these associations so that we can further refine that risk profile to identify which children are really at risk of cancer and at what ages they are at risk of cancer.
Will the observational study continue?
The observational study will also continue. We’d like to enrol additional states, additional registries in order to increase our sample size because even with the ten million births that we do have we’re still not able to look at some particularly rare birth defect cancer associations. So we will proceed with both of those arms of the study simultaneously as we move forward.
Anything you’d like to add?
As I mentioned, the findings from this study show that it’s not just children with some of these recognised chromosomal or genetic syndromes who appear to be at increased risk of cancer but also children with these non-syndromic birth defects. In many cases there are very few established risk factors for paediatric cancers and some of the magnitudes of the associations that we’re seeing here really highlight birth defects as an area that needs further research, not simply in its own right but also in connection with childhood cancer. I hope that this study spurs further investigation, not just into the risk of childhood cancer among children with birth defects but also into the mechanisms by which that association might act.