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

doi:10.18632/oncotarget.27921

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.

Highlights

The importance of complex networks of heterotypic interactions between multiple distinct cell types and regulatory circuits has become widely recognized
It is evident that men with low PSADT values had a much longer pre-treatment period (P < 0.001), sometimes reaching a few years
The small pilot study described in this paper tentatively suggests that there may be an association between a few polymorphic variants of genes controlling neurotransmitter metabolism and the prognosis of prostate cancer (PC)

Summary

INTRODUCTION

The importance of complex networks of heterotypic interactions between multiple distinct cell types (both malignant and normal) and regulatory circuits has become widely recognized. Numerous polymorphic gene variants commonly present in the human genome were shown to mildly influence cancer pathogenesis and tumor progression [9, 10], and it appears that that this genetic variability may contribute to occasionally detected associations between malignancies and non-oncological conditions One of such associations was highlighted by repeated observations of liaisons between emotional stress, depression and chronic psychiatric disorders with the risk of cancer development [11,12,13,14,15,16]. The aim of this small pilot study was to compare the presence of common polymorphic variants of a few genes encoding neurotransmitters in PC patients with the ‘polar’ variants of disease prognosis defined by either very low or very high PSADT values

RESULTS

DISCUSSION

MATERIALS AND METHODS