Patients with autism have increased mutations in genes that drive cancer but decreased rates of cancer

Date: Thursday, April 7, 2016

University of Iowa researchers have shown that patients diagnosed with an autism spectrum disorder (ASD) have more cancer-promoting oncogenes but lower rates of cancer.

The team, led by Benjamin Darbro, assistant professor of medical genetics in the Stead Family Department of Pediatrics at the UI Carver College of Medicine, analyzed large, publicly available genomic databases of patients with autism. They found that autistic patients have significantly higher rates of DNA variation in their cancer-promoting oncogenes than those without autism. The team followed up this result with an analysis of the University of Iowa Hospitals and Clinics’ electronic medical record (EMR) and discovered that patients diagnosed with autism were also less likely to be diagnosed with cancer.

“It’s a very provocative result that makes sense on one level and is extremely perplexing on another,” Darbro says.

The study was published this month in the journal PLOS One.

Darbro and his team used data from the ARRA Autism Sequencing Collaboration and compared them to a control group from the Exome Variant Server database. Patients in the ARRA database had more otherwise-rare coding variants within their cancer-causing oncogenes, but their tumor-suppressor genes carried a normal number of these variants.

The researchers ran numerous controls. As expected, they found that individuals with autism had many more DNA variations in genes associated with autism, epilepsy, and intellectual disability compared to individuals in the control group. There was no difference between the autism and control groups when they examined genes involved in other unrelated conditions.

They then turned their attention to the EMR at UI Hospitals and Clinics and compared 1,837 patients with autism-spectrum disorder to 9,336 patients with any other diagnosis, then determined what proportion of each group was diagnosed with cancer. They found that for children and adults with ASD, only 1.3 percent were also diagnosed with cancer, compared to 3.9 percent of the control patients. However, the cancer rate in patients with ASD did increase with age.

For those under 14 years of age, though, the odds of having cancer were reduced by 94 percent compared to individuals in the same age range without autism. Both males and females with ASD demonstrated this protective effect.

The research team found no relationship between autism and other systemic diseases, such as high blood pressure or diabetes. To demonstrate that the relationship observed between autism and cancer was not due to a technical artifact, they looked for and found no relationship with cancer when they examined the rates of other common conditions, such as heartburn, allergies, and eczema.

ASD is a general term for a group of disorders that affect brain development. Autism is characterized by impaired social interaction, impaired verbal and nonverbal communication skills, and repetitive behaviors. Autism is also one symptom of many inherited cancer syndromes caused by mutations in a single gene.

“The overlap in genes between those known to promote cancer and those implicated in syndromic neurodevelopmental disorders is not new, but what we’ve shown is that this overlap is much broader at the genetic level than previously known and that, somehow, it may translate into a lower risk of cancer,” Darbro says.

The findings raise questions about new ways to treat both cancer and ASD. Could the genetic variants that seem to provide protection against cancer in people with ASD be used to develop new anti-cancer treatments? Or could current cancer drugs that target the genetic pathways found to overlap with ASD also be useful for treating ASD? This last question is already being pursued by other scientists in clinical trials testing the potential benefits of anti-cancer drugs for autism patients.

Other members of the research team include Rohini Singh, M. Bridget Zimmerman, Vinit Mahajan, and Alexander Bassuk.

Story Source: Molly Rossiter, UI Health Care Marketing and Communications, 200 Hawkins Drive, Room W319 GH, Iowa City, Iowa 52242-1009

Media Contact: Jennifer Brown, UI Health Care Marketing and Communications,