The presence of polymorphisms in genes controlling neurotransmitter metabolism and disease prognosis in patients with prostate cancer: a possible link with schizophrenia
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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
|Vladimir N. Anisimov,||email:||[email protected]|
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
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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