Page 264 - EJMO-9-2

Eurasian Journal of
Medicine and Oncology The genetics of chronic stress in cervical lesions

playing a role in the stress response, with implications for mediated by the A variant, supporting the dynamic receptor
HPV infection and cervical lesions. regulation model proposed by Liggett. The discovery of a
47
Although neurotrophins are known to play a role in protective effect associated with the CHRNA5 variant allele
gynecological cancers, including cervical cancer, we highlights how genetic variation can modulate the release
59
found no evidence of any genetic contribution regarding of catecholamines during stress. This adds a new layer of
the studied variants in the neurotrophic factors genes and understanding to how reduced receptor activity impacts
the stress response and its link to HPV-related lesions. The
cervical lesions associated with HPV infection. Previous finding that the 10-repeat allele (SLC6A4) increases risk
studies reported higher expressions of BDNF and NTRK2 provides novel evidence for how serotonergic signaling,
in cervical cancer tissue. 36,60 However, we believe that particularly through SERT, regulates catecholamine secretion
possible slight changes in gene expression associated with and contributes to the physiological stress response in cervical
these variants are not sufficient to promote cervical lesions.
lesion development. By integrating findings from adrenergic,
A limitation of our study is the use of archived samples. cholinergic, and serotonergic systems, this study establishes
We were not able to collect more data on the individuals that a comprehensive view of how these interconnected systems
may be important in this context, such as medical history contribute to the stress response and its downstream effects
related to chronic stress conditions, genetic syndromes on HPV infection and cervical lesion progression. The study
predisposing to cancer, co-morbidities, progression to emphasizes the intricate role of neurotransmitter-related
cancer, type of cervical lesion, HPV genotype, and follow-up genetic variants in modulating the stress response, suggesting
information. Without this information, it may be difficult potential therapeutic targets. These findings pave the way
to control for confounders, potentially leading to biased for personalized approaches to managing HPV infection
associations between variables of interest and outcomes. In and cervical cancer, as genetic variations in stress-response
addition, archived samples represent a specific point in time genes may serve as biomarkers for individual susceptibility.
that may not reflect present population dynamics, disease The study suggests that interventions targeting the stress
prevalence, or environmental exposures. The incidence response, such as β-blockers or serotonergic drugs, could
of cervical lesions has changed over time as a result of hold therapeutic potential for HPV-related lesions, further
HPV vaccination programs around the world. Another advancing precision medicine.
limitation of this work is the lack of information regarding However, we cannot rule out the involvement of other
vitamin imbalances and nutraceutical supplementation, tumorigenic pathways that are unrelated to chronic stress.
since it may play a significant role in women’s health. For instance, ADRB2 is linked to immune cell infiltration,
Alpha-lipoic acid has shown promising effects in cancer suggesting its role in the immune response and tumor
treatment through its multifaceted roles in cellular microenvironment regulation, and enhances the ETS
metabolism and oxidative stress modulation. Research variant transcription factor 1-c-KIT signaling pathway,
indicates that this acid can inhibit cancer cell proliferation promoting tumor progression. 64,65 SLC6A4 evidence
and induce apoptosis across various cancer types. Inositol indicates that the SERT transporter is overexpressed in
61
has also been shown to exert anti-cancer effects through non-small cell lung cancer, where its activity correlates with
various biochemical pathways, making it a promising poor prognosis due to activation of the c-Myc oncogene.
66
candidate for cancer prevention and treatment. Finally, CHRNA5 also plays a pivotal role in cancer development
62
omega-3 fatty acids and their anti-inflammatory effects and progression by modulating key signaling pathways
may help alleviate the side effects of cancer treatments. 63 such as mitogen-activated protein kinase/extracellular
This study further supports the link between stress and signal-regulated kinase, signal transducer and activator of
tumorigenesis, reinforcing the role of chronic stress in transcription 3, and YAP. 67-70
tumorigenesis, particularly in gynecological cancers, by
highlighting the involvement of specific genetic variations 5. Conclusion
in stress-responsive mechanisms. The findings align with Our research elucidates that genetic polymorphisms
and expand upon previous research showing the activation within the adrenergic, cholinergic, and serotonergic
of the autonomic nervous system and HPA in the stress systems contribute significantly to the pathogenesis
response, with downstream effects on tumor biology. of tumorigenesis in cervical lesions associated with
Regarding ADRB2, the identification of the A allele as a risk cervical carcinoma. This investigation substantiates the
factor for HPV infection and cervical lesions emphasizes role of the autonomic nervous system in the biology of
the physiological importance of catecholamine-mediated tumors, in conjunction with the genetic frameworks
stress responses in disease progression. Insights into this underpinning mechanisms pertinent to chronic stress. By
polymorphism provide evidence of a stronger stress response accentuating and contributing to the understanding of the

Volume 9 Issue 2 (2025) 256 doi: 10.36922/EJMO025100047