Otizm ve kanser arasındaki ilişki

Öz

Otizm spektrum bozukluğu (OSB), erken çocuklukta başlayan bir dizi gelişim bozukluğuna işaret etmektedir. Doğumdan sonraki ilk üç yıl içinde, otizm spektrum bozukluğunun erken uyarı belirtileri görünür hale gelmektedir İletişimdeki zorluklar, konuşma gecikmeleri ve sosyalleşme problemlerinden kaynaklanmaktadır. Eğitim ve tedavi kısmen fayda sağlasa da bu durumu tamamen tedavi edebilecek etkili ilaçlar veya cerrahi teknikler bulunmamaktadır. Araştırmacılar, otizm ile nörolojik, gastrointestinal ve kanser hastalıklarının gelişme riskinin artması arasındaki ilişkiyi incelemiştir. Otizm ve kanser arasındaki ilişki hakkında kapsamlı bir araştırma ise net olarak ortaya konmamıştır. Bununla birlikte, otizmle ilgili kanser riskinin bu özel yönüne bakmak, genlere ve yollara özellikle dikkat etmek önemlidir. Makalenin amacı, otizm ile kanser arasındaki olası bir ilişkiye dair mevcut kanıtları literatürdeki çalışmalar ışığında inceleyerek bütüncül bir bakış açısı sunmaktır.

Anahtar Kelimeler

• otizm
• kanser
• genetik

Relationship Between Autism and Cancer

Öz

Autism spectrum disorder (ASD) refers to a set of developmental disorders that appear beginning in early infancy. Within the first three years following birth, early warning signs of autism spectrum disorder become apparent. Their difficulties in communicating stem from speech delays as well as difficulties in socializing. Though education and treatment may be somewhat helpful, there are no effective drugs or surgical techniques that can treat it. Researchers have found a relationship between autism and an increased risk of developing neurological, gastrointestinal, and cancer diseases. A comprehensive study of the relationship between autism and cancer has not been clear. Nonetheless, it is important to look into this particular aspect of autism-related cancer risk, paying special attention to the genes and pathways involved. The aim of this article is to provide a holistic perspective by studying the literature of existing evidence on a possible correlation between autism and cancer.

Anahtar Kelimeler

• Autism
• cancer
• genetics

Kaynakça

1. de Araujo CA. Autism: An ‘epidemic’of contemporary times? J Anal Psychol. 2022;67(1):5-20.
2. Doenyas C, Ekici B, Unay ÖS, Gönen İ, Tatlı B. Autism in Turkey: demographics, behavior problems, and accompanying medical conditions in a sample of Turkish youth with autism spectrum disorder. International Journal of Developmental Disabilities. 2023;69(2):179-89.
3. Rylaarsdam L, Guemez-Gamboa A. Genetic causes and modifiers of autism spectrum disorder. Front Cell Neurosci. 2019;13:385.
4. Özdem B. Microbiota: A Potential Therapy for Autism. Journal of Immunology and Clinical Microbiology. 2020;5(3):97-105.
5. Krigsman A, Walker SJ. Gastrointestinal disease in children with autism spectrum disorders: Etiology or consequence? World journal of psychiatry. 2021;11(9):605.
6. Maman S, Witz IP. A history of exploring cancer in context. Nature Reviews Cancer. 2018;18(6):359-76.
7. Weinberg RA. How cancer arises. Sci Am. 1996;275(3):62-70.
8. Ingudomnukul E, Baron-Cohen S, Wheelwright S, Knickmeyer R. Elevated rates of testosterone-related disorders in women with autism spectrum conditions. Horm Behav. 2007;51(5):597-604.

9. Tabares-Seisdedos R, Rubenstein J. Chromosome 8p as a potential hub for developmental neuropsychiatric disorders: implications for schizophrenia, autism and cancer. Mol Psychiatry. 2009;14(6):563-89.
10. Gannon WT, Martinez JE, Anderson SJ, Swingle HM. Cancer and copy number variants in an autism diagnostic clinic. J Dev Behav Pediatr. 2013;34(5):379-81.
11. Darbro BW, Singh R, Zimmerman MB, Mahajan VB, Bassuk AG. Autism linked to increased oncogene mutations but decreased cancer rate. PLoS One. 2016;11(3):e0149041.
12. Shavelle RM, Strauss DJ, Pickett J. Causes of death in autism. J Autism Dev Disord. 2001;31:569-76.
13. Kao H-T, Buka SL, Kelsey KT, Gruber DF, Porton B. The correlation between rates of cancer and autism: an exploratory ecological investigation. PLoS One. 2010;5(2):e9372.
14. Liu Q, Yin W, Meijsen J, Reichenberg A, Gådin J, Schork A, et al. Cancer risk in individuals with autism spectrum disorder. Ann Oncol. 2022;33(7):713-9.
15. Forés-Martos J, Catalá-López F, Sánchez-Valle J, Ibáñez K, Tejero H, Palma-Gudiel H, et al. Transcriptomic metaanalyses of autistic brains reveals shared gene expression and biological pathway abnormalities with cancer. Mol Autism. 2019;10:1-16.
16. Chiang H-L, Liu C-J, Hu Y-W, Chen S-C, Hu L-Y, Shen C-C, et al. Risk of cancer in children, adolescents, and young adults with autistic disorder. The Journal of Pediatrics. 2015;166(2):418-23. e1.
17. Bunney TD, Katan M. Phosphoinositide signalling in cancer: beyond PI3K and PTEN. Nature Reviews Cancer. 2010;10(5):342-52.
18. Ciuffreda L, Di Sanza C, Incani UC, Milella M. The mTOR pathway: a new target in cancer therapy. Curr Cancer Drug Targets. 2010;10(5):484-95.
19. Yavuz BR, Arici MK, Demirel HC, Tsai C-J, Jang H, Nussinov R, et al. Neurodevelopmental disorders and cancer networks share pathways, but differ in mechanisms, signaling strength, and outcome. NPJ Genomic Medicine. 2023;8(1):37.
20. Serajee F, Nabi R, Zhong H, Huq AM. Association of INPP1, PIK3CG, and TSC2 gene variants with autistic disorder: implications for phosphatidylinositol signalling in autism. J Med Genet. 2003;40(11):e119-e.
21. Chen J, Alberts I, Li X. Dysregulation of the IGF-I/PI3K/AKT/mTOR signaling pathway in autism spectrum disorders. Int J Dev Neurosci. 2014;35:35-41.
22. Enriquez-Barreto L, Morales M. The PI3K signaling pathway as a pharmacological target in Autism related disorders and Schizophrenia. Molecular and cellular therapies. 2016;4:1-12.
23. Wang H, Doering LC. Reversing autism by targeting downstream mTOR signaling. Front Cell Neurosci. 2013;7:28.
24. Ling Y, Du Q. FGF10/FGF17 as prognostic and drug response markers in acute myeloid leukemia. Current Research in Translational Medicine. 2022;70(1):103316.
25. Wei R, Yehia L, Ni Y, Eng C. The mitochondrial genome as a modifier of autism versus cancer phenotypes in PTEN hamartoma tumor syndrome. Human Genetics and Genomics Advances. 2023;4(3).
26. Gabrielli AP, Manzardo AM, Butler MG. GeneAnalytics pathways and profiling of shared autism and cancer genes. Int J Mol Sci. 2019;20(5):1166.
27. Smith IN, Dawson JE, Eng C. Comparative Protein Structural Network Analysis Reveals C-Terminal Tail Phosphorylation Structural Communication Fingerprint in PTEN-Associated Mutations in Autism and Cancer. The Journal of Physical Chemistry B. 2023;127(3):634-47.
28. Frazier TW, Embacher R, Tilot AK, Koenig K, Mester J, Eng C. Molecular and phenotypic abnormalities in individuals with germline heterozygous PTEN mutations and autism. Mol Psychiatry. 2015;20(9):1132-8.
29. Yehia L, Ni Y, Feng F, Seyfi M, Sadler T, Frazier TW, et al. Distinct alterations in tricarboxylic acid cycle metabolites associate with cancer and autism phenotypes in Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome. The American Journal of Human Genetics. 2019;105(4):813-21.
30. Yehia L, Ni Y, Sadler T, Frazier TW, Eng C. Distinct metabolic profiles associated with autism spectrum disorder versus cancer in individuals with germline PTEN mutations. NPJ Genomic Medicine. 2022;7(1):16.
31. Crawley JN, Heyer W-D, LaSalle JM. Autism and cancer share risk genes, pathways, and drug targets. Trends Genet. 2016;32(3):139-46.
32. Rosner M, Hanneder M, Siegel N, Valli A, Fuchs C, Hengstschläger M. The mTOR pathway and its role in human genetic diseases. Mutation Research/reviews in Mutation Research. 2008;659(3):284-92.
33. Costa-Mattioli M, Sossin WS, Klann E, Sonenberg N. Translational control of long-lasting synaptic plasticity and memory. Neuron. 2009;61(1):10-26.
34. Bae SM, Hong JY. The Wnt signaling pathway and related therapeutic drugs in autism spectrum disorder. Clinical Psychopharmacology and Neuroscience. 2018;16(2):129.
35. Janssens N, Janicot M, Perera T. The Wnt-dependent signaling pathways as target in oncology drug discovery. Invest New Drugs. 2006;24:263-80.
36. Aoki K, Taketo MM. Adenomatous polyposis coli (APC): a multi-functional tumor suppressor gene. J Cell Sci. 2007;120(19):3327-35.
37. Zhou XL, Giacobini M, Anderlid BM, Anckarsäter H, Omrani D, Gillberg C, et al. Association of adenomatous polyposis coli (APC) gene polymorphisms with autism spectrum disorder (ASD). American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. 2007;144(3):351-4.
38. Lee E, Salic A, Kruger R, Heinrich R, Kirschner MW. The roles of apc and axin derived from experimental and theoretical analysis of the wnt pathway. PLoS Biol. 2004;2(3):405-6.
39. Cotter D, Kerwin R, Al-Sarraji S, Brion JP, Chadwich A, Lovestone S, et al. Abnormalities of Wnt signalling in schizophrenia–evidence for neurodevelopmental abnormality. Neuroreport. 1998;9(7):1379-83.
40. Zhou J, Parada LF. PTEN signaling in autism spectrum disorders. Curr Opin Neurobiol. 2012;22(5):873-9.
41. Ratner N, Miller SJ. A RASopathy gene commonly mutated in cancer: the neurofibromatosis type 1 tumour suppressor. Nature Reviews Cancer. 2015;15(5):290-301.
42. Sanchez-Ortiz E, Cho W, Nazarenko I, Mo W, Chen J, Parada LF. NF1 regulation of RAS/ERK signaling is required for appropriate granule neuron progenitor expansion and migration in cerebellar development. Genes Dev. 2014;28(21):2407-20.
43. Campen CJ, Gutmann DH. Optic pathway gliomas in neurofibromatosis type 1. J Child Neurol. 2018;33(1):73-81.
44. Rossant J, Tam PP. Exploring early human embryo development. Science. 2018;360(6393):1075-6.
45. Fouad YA, Aanei C. Revisiting the hallmarks of cancer. Am J Cancer Res. 2017;7(5):1016.
46. Huang G-H, Sun Z-L, Li H-J, Feng D-F. Rho GTPase-activating proteins: Regulators of Rho GTPase activity in neuronal development and CNS diseases. Mol Cell Neurosci. 2017;80:18-31.
47. Kim EK, Choi E-J. Pathological roles of MAPK signaling pathways in human diseases. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease. 2010;1802(4):396-405.
48. Kyosseva SV. Targeting MAPK signaling in age-related macular degeneration. Ophthalmol Eye Dis. 2016;8:OED. S32200.
49. Santarpia L, Lippman SM, El-Naggar AK. Targeting the MAPK–RAS–RAF signaling pathway in cancer therapy. Expert Opin Ther Targets. 2012;16(1):103-19.
50. Ryu H-H, Lee Y-S. Cell type-specific roles of RAS-MAPK signaling in learning and memory: Implications in neurodevelopmental disorders. Neurobiol Learn Mem. 2016;135:13-21.
51. Anthoney N, Foldi I, Hidalgo A. Toll and Toll-like receptor signalling in development. Development. 2018;145(9):dev156018.
52. Ehninger D, Silva AJ. Rapamycin for treating Tuberous sclerosis and Autism spectrum disorders. Trends Mol Med. 2011;17(2):78-87.