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Gene & Protein in Disease Association of GST1 with lung cancer

line A549 exhibits significantly higher mRNA and protein cancer. In our study, no significant bias was observed in
expression of GSTA1, as confirmed by real-time PCR and the allelic or genotypic distribution of rs743590 among
Western blotting assays, respectively, in comparison to patients and controls. However, this SNV was identified
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MRC-5 normal lung cells. Adnan et al. demonstrated that as a candidate risk rSNV for lung cancer through our
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siRNA-mediated downregulation of GSTA1 significantly bioinformatic pipeline. Although the variant might not
increased cell proliferation in the CACO cell line, while Liu act as a susceptibility locus in the selected population,
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et al. demonstrated that GSTA1 overexpression facilitated it could be significant in other populations, as is often
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cell proliferation in the A549 cell line. In a related finding, the case with cancer-associated SNVs. Identifying such
Caco-2 cells with low GSTA1 expression exhibited a notably SNVs will assist in the discovery of population-specific
higher incidence of apoptosis induced by tumor necrosis biomarkers for genetic susceptibility to lung cancer, which
factor-alpha/butyrate, as well as increased cell proliferation is a stepping stone toward more precise mutation analysis
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mediated by JNK signaling. Moreover, transcription through genome sequencing.
factors regulating GSTA1, specifically REST, ESRRA, and
TBX5, have been implicated in lung cancer. 35 5. Conclusion
Although the SNV in question, rs2207950, has not We investigated the genetic association of two rSNVs
been previously associated with lung cancer, it has been that had been identified as potential risk factors for lung
reported to be associated with myocardial infarction carcinogenesis through a comprehensive bioinformatic
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among African Americans and with bipolar disorder. pipeline. Our findings indicate an over-representation
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In our comprehensive study, we found that the GSTA1 of the GSTA1 rs2207950 AA genotype among individuals
rs2207950 AA genotype is disproportionately prevalent with lung cancer. To the best of our knowledge, the present
among smokers with lung cancer. According to the GTEx study represents the first endeavor to explore the influence
database (Figure 1), normalized expression of GSTA1 of rs2207950 on individual susceptibility to lung cancer. The
in lung tissue is lower for the AA genotype compared to risk genotype is associated with reduced GSTA1 expression
the other two genotypes. This diminished expression may compared to the other two genotypes, which may impair
impair the body’s detoxification capability for carcinogens the ability to detoxify cigarette smoke-related xenobiotics,
and reactive oxygen species, potentially heightening thereby contributing to the development of lung cancer.
susceptibility to different diseases, including cancer. Data Identifying rSNVs in specific populations will not only
analysis from healthy cadaver lung tissue (obtained from enhance our understanding of genetic susceptibility
the GTEx database) and lung cancer tissue (obtained but will also contribute to the development of tailored
from the PancanQTL webserver) have already revealed therapies based on precision medicine. This approach can
the A allele as a risk factor. It is also worth mentioning also support the formulation of more effective tobacco
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that GSTA1 expression has profound consequences on control legislation and genetic counseling strategies.
protection against cytotoxic byproducts of inflammation. 38 Acknowledgments
SULT1A1 is involved in the biotransformation None.
of xenobiotic procarcinogens into carcinogens.
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Consequently, its upregulation is believed to increase the Funding
cell’s susceptibility to malignant transformation through
carcinogenic activation. The Arg213His polymorphism The study was funded by the Departmental BI grant,
in SULT1A1 has been identified as a high-risk factor Department of Genetics, University of Calcutta (grant no.: 97).
for breast cancer in Asian women and postmenopausal Conflict of interest
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women globally. In addition, in combination with
NAT2 fast acetylator status, this polymorphism further The authors declare no conflicts of interest.
elevates breast cancer risk in women exposed to tobacco
smoke. The Arg213His variant has also been predicted Author contributions
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to modulate the association between smoking and oral Conceptualization: Arpan Saha, Mainak Sengupta
cancer. The differential expression of SULT1A1 in lung Data Curation: Debmalya Sengupta
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cancer, compared to healthy tissues, suggests its potential Formal analysis: Arpan Saha
as a biomarker for xenobiotic-induced carcinogenesis. Investigation: Arpan Saha, Souradeep Banerjee, Ritabrata
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While rs743590 has been linked to enhancer-based Mitra, Abhijit Sarkar, Tamohan Chaudhuri,
immune dysregulation in type 1 diabetes in the European Gautam Bhattacharjee, Somsubhra Nath, Susanta
population, it has not yet been associated with lung Roychoudhury, Mainak Sengupta
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Volume 3 Issue 3 (2024) 6 doi: 10.36922/gpd.3928