Autism Linked to Increased Oncogene Mutations but Decreased Cancer Rate

Benjamin W Darbro; Rohini Singh; M Bridget Zimmerman; Vinit B Mahajan; Alexander G Bassuk

doi:10.1371/journal.pone.0149041

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Autism Linked to Increased Oncogene Mutations but Decreased Cancer Rate

Journal article

Open access

Peer reviewed

Autism Linked to Increased Oncogene Mutations but Decreased Cancer Rate

Benjamin W Darbro, Rohini Singh, M Bridget Zimmerman, Vinit B Mahajan and Alexander G Bassuk

PLoS One, Vol.11(3), e0149041

2016

DOI: 10.1371/journal.pone.0149041

PMCID: PMC4774916

PMID: 26934580

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Abstract

Autism spectrum disorder (ASD) is one phenotypic aspect of many monogenic, hereditary cancer syndromes. Pleiotropic effects of cancer genes on the autism phenotype could lead to repurposing of oncology medications to treat this increasingly prevalent neurodevelopmental condition for which there is currently no treatment. To explore this hypothesis we sought to discover whether autistic patients more often have rare coding, single-nucleotide variants within tumor suppressor and oncogenes and whether autistic patients are more often diagnosed with neoplasms. Exome-sequencing data from the ARRA Autism Sequencing Collaboration was compared to that of a control cohort from the Exome Variant Server database revealing that rare, coding variants within oncogenes were enriched for in the ARRA ASD cohort (p<1.0 x 10(-8)). In contrast, variants were not significantly enriched in tumor suppressor genes. Phenotypically, children and adults with ASD exhibited a protective effect against cancer, with a frequency of 1.3% vs. 3.9% (p<0.001), but the protective effect decreased with age. The odds ratio of neoplasm for those with ASD relative to controls was 0.06 (95% CI: 0.02, 0.19; p<0.0001) in the 0 to 14 age group; 0.35 (95% CI: 0.14, 0.87; p = 0.024) in the 15 to 29 age group; 0.41 (95% CI: 0.15, 1.17; p = 0.095) in the 30 to 54 age group; and 0.49 (95% CI: 0.14, 1.74; p = 0.267) in those 55 and older. Both males and females demonstrated the protective effect. These findings suggest that defects in cellular proliferation, and potentially senescence, might influence both autism and neoplasm, and already approved drugs targeting oncogenic pathways might also have therapeutic value for treating autism.

Mutation

Oncogenes

Autism Spectrum Disorder - genetics

Genetic Predisposition to Disease

Prevalence

Humans

Middle Aged

Autism Spectrum Disorder - complications

Child, Preschool

Infant

Male

Young Adult

Neoplasms - genetics

Adolescent

Adult

Female

Child

Genes, Tumor Suppressor

Neoplasms - epidemiology

Details

Title: Subtitle: Autism Linked to Increased Oncogene Mutations but Decreased Cancer Rate
Creators: Benjamin W Darbro - University of Iowa, Stead Family Department of Pediatrics
Rohini Singh - Department of Pediatrics, Division of Pediatric Hematology/Oncology/BMT, University of Iowa, Iowa City, Iowa, United States of America
M Bridget Zimmerman - University of Iowa, Biostatistics
Vinit B Mahajan - University of Iowa, Stead Family Department of Pediatrics
Alexander G Bassuk - University of Iowa, Stead Family Department of Pediatrics
Resource Type: Journal article
Publication Details: PLoS One, Vol.11(3), e0149041
DOI: 10.1371/journal.pone.0149041
PMID: 26934580
PMCID: PMC4774916
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: United States
Grant note: T32 HL080070-01 / NHLBI NIH HHS
Language: English
Date published: 2016
Academic Unit: Neurology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Biostatistics; Medical Genetics and Genomics; Neurology (Pediatrics)
Record Identifier: 9983769800202771

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