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Research Papers:

The presence of polymorphisms in genes controlling neurotransmitter metabolism and disease prognosis in patients with prostate cancer: a possible link with schizophrenia

Gennady M. Zharinov, Sergei E. Khalchitsky, Alexandre Loktionov, Marina V. Sogoyan, Yulia V. Khutoryanskaya, Natalia Yu. Neklasova, Oleg A. Bogomolov, Ilya V. Smirnov, Marina P. Samoilovich, Vladimir N. Skakun, Sergei V. Vissarionov and Vladimir N. Anisimov _

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Oncotarget. 2021; 12:698-707. https://doi.org/10.18632/oncotarget.27921

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Abstract

Gennady M. Zharinov1,*, Sergei E. Khalchitsky2,*, Alexandre Loktionov3, Marina V. Sogoyan2, Yulia V. Khutoryanskaya4, Natalia Yu. Neklasova1, Oleg A. Bogomolov1, Ilya V. Smirnov1, Marina P. Samoilovich1, Vladimir N. Skakun5, Sergei V. Vissarionov2 and Vladimir N. Anisimov6

1 A.M. Granov Russian Research Center for Radiology and Surgical Technologies of the Ministry of Health of the Russian Federation, Pesochny, St. Petersburg, 197758, Russia

2 H. Turner National Medical Research Center for Children's Orthopedics and Trauma Surgery of the Ministry of Health of the Russian Federation, Pushkin, St. Petersburg, 196603, Russia

3 DiagNodus Ltd, Babraham Research Campus, Cambridge, CB22 3AT, United Kingdom

4 St. Petersburg State Pediatric Medical University of the Ministry of Health of the Russian Federation, St. Petersburg, 194100, Russia

5 Yaroslav-the-Wise Novgorod State University of the Ministry of Science and Higher Education of the Russian Federation, Veliky Novgorod, 173003, Russia

6 N.N. Petrov National Medical Research Center of Oncology, Pesochny, St. Petersburg, 197758, Russia

* These authors contributed equally to this work

Correspondence to:

Vladimir N. Anisimov,email: aging@mail.ru

Keywords: prostate cancer; prostate-specific antigen; disease prognosis; neurotransmitters metabolism genes; psychiatric disorders

Received: February 11, 2021     Accepted: March 08, 2021     Published: March 30, 2021

Copyright: © 2021 Zharinov et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

Polymorphisms of neurotransmitter metabolism genes were studied in patients with prostate cancer (PC) characterized by either reduced or extended serum prostate-specific antigen doubling time (PSADT) corresponding to unfavorable and favorable disease prognosis respectively. The ‘unfavorable prognosis’ group (40 cases) was defined by PSADT ≤ 2 months, whereas patients in the ‘favorable prognosis’ group (67 cases) had PSADT ≥ 30 months. The following gene polymorphisms known to be associated with neuropsychiatric disorders were investigated: a) the STin2 VNTR in the serotonin transporter SLC6A4 gene; b) the 30-bp VNTR in the monoamine oxidase A MAOA gene; c) the Val158Met polymorphism in the catechol-ortho-methyltransferase COMT gene; d) the promoter region C-521T polymorphism and the 48 VNTR in the third exon of the dopamine receptor DRD4 gene.

The STin2 12R/10R variant of the SLC6A4 gene (OR = 2.278; 95% CI = 0.953–5.444) and the -521T/T homozygosity of the DRD4 gene (OR = 1.579; 95% CI = 0.663–3.761) tended to be overrepresented in PC patients with unfavorable disease prognosis. These gene variants are regarded as protective against schizophrenia, and the observed trend may be directly related to a reduced PC risk described for schizophrenia patients. These results warrant further investigation of the potential role of neurotransmitter metabolism gene polymorphisms in PC pathogenesis.


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