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Reduced Risk of Cancer in Schizophrenia, a Bridge Toward Etio-Pathology and Therapy of Both Diseases

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Epigenetics Territory and Cancer

Abstract

Schizophrenia (SCZ), a major mental disease, is associated with reduced risk for different types of cancers, with the exception of breast, endometrial and pancreatic cancers. The lower risk of cancer in first-degree relatives of SCZ patients rules out the drug effects as the cause of reduced cancer risk in SCZ. While genetic polymorphisms were attributed to the reduced cancer risk in SCZ, since hundreds of genes have been linked to SCZ and the effect size of each gene is small (< 1 %), the reduced cancer risk cannot be due to specific genetic polymorphisms. The same is true in cancer, as specific genetic changes are correlated to only 5–10 % of all cancers.

In post-mortem brain studies we found abnormal DNA methylation of the regulatory regions of several genes such as RELN, MB-COMT, MAOA, 5-HTT and HTR2A associated with corresponding altered expression in SCZ patients. As a subset of these epigenetic alterations (e.g. MB-COMT, HTR2A, and 5-HTT) are retained in DNA derived from the saliva of drug naïve SCZ patients, these alterations are not limited to brain and are independent of drug use. In addition to RELN, MB-COMT and MAOA, dysfunctionality of TGFβ, immune system, VGEF, FOXO and specific miRNAs are linked to both SCZ and cancer. Interestingly, the changes in SCZ are often opposite in nature to those observed in cancer suggesting that they may predispose to SCZ, but reduce cancer risk. Therefore, knowledge from one disease may help to understand the molecular basis of the other disease and assist the implementation of therapeutic strategies.

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Abbreviations

5-HTT:

5-hydroxytryptamine (serotonin) transporter

BD:

Bipolar Disorder

BMP:

Bone Morphogenetic Protein

COMT:

Catechol-O- Methyltransferase

DNMT1:

DNA Methyltransferase 1

DRD1:

Dopamine Receptor type 1

DRD2:

Dopamine Receptor type 2

FOXO:

O subclass of the Forkhead Family of Transcription Factors

GABA:

Gamma Amino Butyric Acid

GAD1:

Glutamate decarboxylase 1

HAP1:

Huntingtin Associated Protein 1

HD:

Huntington’s Disease

HIP:

Huntingtin Interacting Protein

HTR2A:

Hydroxytriptamine (serotonin) type 2 receptor

MAOA:

Mono Amine Oxidase A

MB-COMT:

Membrane-Bound Catechol-O-Methyltransferase

MDD:

Major Depressive Disorder

MHC:

Major Histocompatibility Complex

MIA:

Maternal Immune Activation

PD:

Parkinson’s Disease

RELN:

Reelin

SCZ:

Schizophrenia

SSRIs:

Serotonin Specific Reuptake Inhibitors

TGF-β:

Transforming growth factor beta

VEGF:

Vascular Endothelial Growth Factor

VEGFR2:

VEGF receptor 2

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Authors and Affiliations

  1. Department of Surgery, Laboratory of Nutrition and Metabolism at BIDMC, Harvard Medical School, Boston, MA, USA

    Mohamad Reza Eskandari, Hamid Mostafavi Abdolmaleky & Jin-Rong Zhou

  2. Department of Psychiatry, Zanjan University of Medical Sciences, Zanjan, Iran

    Mohamad Reza Eskandari

  3. Department of Medicine (Biomedical Genetics Section), Boston University School of Medicine, Boston, MA, USA

    Hamid Mostafavi Abdolmaleky & Sam Thiagalingam

  4. Department of Genetics & Genomics, Boston University School of Medicine, Boston, MA, USA

    Hamid Mostafavi Abdolmaleky & Sam Thiagalingam

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  1. Mohamad Reza Eskandari
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  2. Hamid Mostafavi Abdolmaleky
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  3. Jin-Rong Zhou
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  4. Sam Thiagalingam
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Correspondence to Mohamad Reza Eskandari .

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  1. Tehran University of Medical Sciences, Department of Medical Genetics School Of Medicine, Tehran, Iran

    Parvin Mehdipour

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Eskandari, M., Abdolmaleky, H., Zhou, JR., Thiagalingam, S. (2015). Reduced Risk of Cancer in Schizophrenia, a Bridge Toward Etio-Pathology and Therapy of Both Diseases. In: Mehdipour, P. (eds) Epigenetics Territory and Cancer. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-9639-2_5

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