Photo by Darren Baker
New research suggests that patients diagnosed with an autism spectrum disorder (ASD) have a higher burden of mutations in oncogenes but lower rates of cancer than the rest of the population.
Investigators analyzed large, publicly available genomic databases of patients with ASD and found that, compared to a set of control subjects, ASD patients had significantly higher rates of DNA variation in oncogenes.
The team followed up this result with an analysis of the University of Iowa Hospitals and Clinics’ electronic medical record and discovered that ASD patients were also significantly less likely to have a co-occurring diagnosis of cancer.
“It’s a very provocative result that makes sense on one level and is extremely perplexing on another,” said Benjamin Darbro, MD, PhD, of the University of Iowa Carver College of Medicine in Iowa City.
Dr Darbro and his colleagues discussed the result, and the research that led to it, in a paper published in PLOS ONE.
The investigators used exome sequencing data from the ARRA Autism Sequencing Collaboration and compared that data to a control cohort from the Exome Variant Server database.
This revealed that rare, coding variants within oncogenes were greatly enriched in the ARRA ASD cohort. By comparison, variants were not significantly enriched in tumor suppressor genes.
To ensure the genetic differences were not technical artifacts but actually bona fide differences in genetic architecture in ASD, the investigators ran numerous controls.
As expected, they found that individuals with ASD had many more DNA variations in genes previously associated with autism, epilepsy, and intellectual disability compared to control individuals.
However, there was no difference between the ASD and control groups when it came to genes involved in other, unrelated conditions such as skeletal dysplasia, retinitis pigmentosa, dilated cardiomyopathy, and non-syndromic hearing loss.
The investigators then turned their attention to the electronic medical record at the University of Iowa Hospitals and Clinics and conducted a retrospective case-control analysis comparing 1837 patients with ASD to 9336 patients with any other diagnosis, and determined what proportion of each group carried a cancer diagnosis.
The team found that, for children and adults with ASD, there appeared to be a protective effect against cancer. The cancer incidence was 1.3% for patients with ASD and 3.9% for controls.
The protective effect was evident in both males and females with ASD, but it was strongest for the youngest group of patients and decreased with age. For ASD patients who were under 14 years of age, the odds of having cancer were reduced by 94% compared to controls.
When the investigators determined the rates of other systemic diseases—such as high blood pressure and diabetes—in the ASD population, they found no relationship.
Furthermore, the team found no relationship with cancer when they examined the rates of other common conditions such as esophageal reflux, allergic rhinitis, atopic dermatitis, and short stature. They said this demonstrated that the inverse relationship observed between ASD and cancer is not due to a technical artifact.
