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Gene & Protein in Disease Association of GST1 with lung cancer

lung cancer and healthy smoker controls. However, Our analysis revealed a discernible trend associating
a significant difference in genotype distribution was the presence of the AA genotype of rs2207950 with
observed under the recessive model of assessment. The an increased risk of lung cancer. GSTA1 belongs to
AA genotype, in comparison to the GG+AG genotype, was the glutathione S-transferases (GSTs) family of drug
significantly over-represented in the smoker lung cancer detoxification enzymes, which play a pivotal role in Phase
group (P = 0.022; OR = 2.7), suggesting it is a potential II xenobiotic metabolism by conjugating glutathione
risk factor. In contrast, no significant association was to a variety of electrophilic substances. 25,26 GSTs are also
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found between either alleles or genotypes with respect to involved in the detoxification of lipid peroxidation, and
rs743590. Table 1 presents the allele and genotype counts GST isoenzymes are known to modulate cell signaling
and frequencies for both selected SNVs in the smokers pathways that regulate cell proliferation and apoptotic
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with lung cancer and healthy smoker groups, along with cell death. GSTA1 has been implicated in several types
the corresponding statistical analysis. of cancer. For instance, high GSTA1 levels have been
correlated with the prognosis of hepatocellular carcinoma
4. Discussion (HCC), where GSTA1 is predicted to effectively inhibit
Lung cancer has long been recognized as being caused by tumorigenesis in HCC by targeting the AMPK/mTOR. 28
cigarette smoking, primarily due to prolonged exposure to However, there is a conflicting understanding regarding
approximately 70 different carcinogens found in cigarette the availability of the GSTA1 enzyme and its role in tumor
smoke. The ability of XMGs to detoxify harmful chemicals progression. While some studies suggest that under-
and eliminate them from the body plays a significant role expression of this enzyme may lead to cancer progression,
in individual susceptibility to lung cancer. Differential others claim that higher production of GSTA1 might also
expression of a variety of XMGs has been reported in increase the risk of cancer. 29,30 Promoter polymorphisms
smokers with lung cancer. 22,23 rSNVs in the cis-elements in GSTA1 have been shown to alter its transcriptional
of these genes, which modulate gene transcription, are activity, conferring susceptibility to carcinogen-induced
often implicated in this differential expression. In this cellular transformations. A correlation has been identified
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24
regard, we investigated the association of two prioritized between GSTA1 genotypes associated with reduced GSTA1
rSNVs: rs2207950 and rs743590, in the XMGs GSTA1 and transcription and an elevated risk of breast cancer, particularly
SULT1A1, respectively, with lung cancer in an eastern among women with a lower intake of cruciferous vegetables
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Indian population. and those who smoke. In addition, the lung cancer cell
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Table 1. Distribution of alleles and genotypes among smokers with lung cancer and healthy smoker controls for GSTA1
rs2207950 and SULT1A1 rs743590

Gene/ID of Genotypes/ Smoker with lung Healthy smoker Comparisons of different OR (95% CI) P‑value
polymorphism alleles cancer (n=101) (%) control (n=252) (%) models
GSTA1/rs2207950 AA 12 (11.88) 12 (4.76) Dominant (AG+AA) versus GG 1.31 (0.82 – 2.09) 0.26
AG 48 (47.52) 121 (48.01) Co-dominant GG versus AG 2.90 (1.21 – 6.97) 0.062
versus AA
GG 41 (40.59) 119 (47.22) Recessive AA versus (GG+AG) 2.70 (1.17 – 6.22) 0.022
Alleles
A 72 (35.64) 145 (28.77) NA 0.0736
G 130 (64.36) 359 (71.23)
SULT1A1/rs743590 AA 3 (3.57) 8 (3.17) Dominant (AG+AA) versus GG 1.23 (0.71 – 2.10) 0.45
AG 24 (28.57) 62 (24.60) Co-Dominant GG versus AG 1.20 (0.71 – 2.16) 0.75
versus AA
GG 57 (67.86) 182 (72.22) Recessive AA versus (GG+AG) 1.13 (0.29 – 4.36) 0.86
Alleles
A 30 (17.86) 78 (15.48) NA 0.4668
G 138 (82.14) 426 (84.52)
Notes: Pearson’s Chi-square test was performed to determine allelic associations with lung cancer. Multivariate logistic regression was conducted using
dominant, co-dominant, and recessive models to establish genotypic associations with lung cancer. Significance levels: P<0.05. Restriction fragment
length polymorphism could not be performed among 17 patient samples for SULT1A1 rs743590 due to repeated amplification failures.

Volume 3 Issue 3 (2024) 5 doi: 10.36922/gpd.3928