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Research explores the potential function of gene polymorphisms in pathogenesis of prostate most cancers

Oncotarget published “The presence of polymorphisms in genes that control neurotransmitter metabolism and disease prognosis in patients with prostate cancer: a possible link with schizophrenia” Serum prostate-specific antigen doubling time corresponding to unfavorable or favorable disease prognosis.

The following gene polymorphisms known to be associated with neuropsychiatric disorders have been studied:

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 C-521T polymorphism of the promoter region and the 48 VNTR in the third exon of the dopamine receptor DRD4 gene.

The STin2 12R / 10R variant of the SLC6A4 gene and the -521T / T homozygosity of the DRD4 gene tended to be overrepresented in PC patients with an unfavorable disease prognosis.

These gene variants are believed to protect against schizophrenia, and the trend observed could be directly related to a reduced PC risk described for schizophrenia patients.

These results warrant further investigation into the potential role of gene polymorphisms of neurotransmitter metabolism in PC pathogenesis.

The importance of complex networks of heterotypical interactions between several different cell types (both malignant and normal) and regulatory circuits is now widely recognized. “

Dr. Vladimir N. Anisimov, Petrov National Medical Research Center for Oncology

The traditional tumor-centric view, focusing solely on malignant cell populations, has largely been replaced by a concept of the tumor microenvironment, the latter viewed as a “dynamic arena of interaction” in which tumor cells interact with the extracellular matrix, resident and recruited cells and soluble factors “.

Although there is general consensus that chronic stress and depression tend to impair immune responses and facilitate cancer development and progression, the risk of developing some cancers appears to be reduced in those with schizophrenia.

Not only is pancreatic cancer the second most common cancer in men, it is also a disease characterized by a wide range of severity levels, from indolent to highly aggressive.

The latter feature of PC makes tumor growth monitoring a very important prerequisite for successful disease management, and the repeated measurement of the concentration of a blood biomarker of PC, the prostate-specific antigen, is widely accepted as an important prognostic tool for routine patient monitoring with it . Condition.

It was pointed out above that psychiatric illnesses can be associated with a greatly altered PC risk, but little is known about possible influences of the patient’s genetic background on this phenomenon as well as on the prognosis of illness in an already existing PC.

The Anisimov research team concluded in their Oncotarget research output that oncological diseases are known to be less common in schizophrenia patients and that this phenomenon mainly affects men, although this phenomenon is particularly pronounced in PC.

Interestingly, PC has emerged recently as a cancer, the development of which is heavily dependent on neurogenic regulatory pathways provided by growing nerves as an important TME component.

In addition, neurotransmitters such as serotonin and dopamine are now viewed as important factors that modulate neoplastic growth by influencing angiogenesis and neoplastic cell proliferation.

The results presented in this paper show that the presence of certain polymorphic variants of the SLC6A4 and DRD4 genes in connection with serotonin and dopamine signaling pathways seems to correlate with PC prognosis.

Further larger studies are needed to clarify the role of gene polymorphisms in neurotransmitter metabolism in PC pathogenesis.


Journal reference:

Devall, MA M & Casey, G., (2021) The control of cellular heterogeneity by single-cell deconvolution of gene expression reveals new markers for colorectal tumors with microsatellite instability. Onkoziel. doi.org/10.18632/oncotarget.27935.

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