TY - JOUR

T1 - The presence of polymorphisms in genes controlling neurotransmitter metabolism and disease prognosis in patients with prostate cancer

T2 - A possible link with schizophrenia

AU - Zharinov, Gennady M.

AU - Khalchitsky, Sergei E.

AU - Loktionov, Alexandre

AU - Sogoyan, Marina V.

AU - Khutoryanskaya, Yulia V.

AU - Neklasova, Natalia Yu

AU - Bogomolov, Oleg A.

AU - Smirnov, Ilya V.

AU - Samoilovich, Marina P.

AU - Skakun, Vladimir N.

AU - Vissarionov, Sergei V.

AU - Anisimov, Vladimir N.

N1 - Publisher Copyright: 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.

PY - 2021/3/30

Y1 - 2021/3/30

N2 - 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.

AB - 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.

KW - Disease prognosis

KW - Neurotransmitters metabolism genes

KW - Prostate cancer

KW - Prostate-specific antigen

KW - Psychiatric disorders

UR - http://www.scopus.com/inward/record.url?scp=85105114481&partnerID=8YFLogxK

U2 - 10.18632/ONCOTARGET.27921

DO - 10.18632/ONCOTARGET.27921

M3 - Article

AN - SCOPUS:85105114481

VL - 12

SP - 698

EP - 707

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 7

ER -