ArticlePloS one2016
The rs3957357C>T SNP in GSTA1 Is Associated with a Higher Risk of Occurrence of Hepatocellular Carcinoma in European Individuals.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 19 citations in OpenAlex.
- GSTA1 deficiency drives neuroendocrine differentiation via TNFRSF13B/c-FOS/CHGA axis in prostate cancer.International journal of biological sciences · 2026Article
- Glutathione S-transferase Omega 2 DD genotype is associated with an increased risk of sporadic amyotrophic lateral sclerosis in Chinese men.The Journal of international medical research · 2021Article
- Glutathione-S-transferases genes-promising predictors of hepatic dysfunction.World journal of hepatology · 2021Review
- Collagen type XVIII alpha 1 chain (COL18A1) variants affect the risk of anti-tuberculosis drug-induced hepatotoxicity: A prospective study.Journal of clinical laboratory analysis · 2021Article
- Fermentable fiber-induced hepatocellular carcinoma in mice recapitulates gene signatures found in human liver cancer.PloS one · 2020Article
- Glutathione S-transferase A1 suppresses tumor progression and indicates better prognosis of human primary hepatocellular carcinoma.Journal of Cancer · 2020Article
- Effects ofNeuropsychiatric disease and treatment · 2020Article
- Pharmacogenetics of hepatocellular carcinoma and cholangiocarcinoma.Cancer drug resistance (Alhambra, Calif.) · 2019Review
- Observational
- SeqVItA: Sequence Variant Identification and Annotation Platform for Next Generation Sequencing Data.Frontiers in genetics · 2018Article
- XRCC1 and XPD polymorphisms and their relation to the clinical course in hepatocarcinoma patients.Oncology letters · 2017Article
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glutathione S-transferases (GSTs) detoxify toxic molecules by conjugation with reduced glutathione and regulate cell signaling. Single nucleotide polymorphisms (SNPs) of GST genes have been suggested to affect GST functions and thus to increase the risk of human hepatocellular carcinoma (HCC). As GSTA1 is expressed in hepatocytes and the rs3957357C>T (TT) SNP is known to downregulate GSTA1 mRNA expression, the aims of this study were: (i) to explore the relationship between the TT SNP in GSTA1 and the occurrence of HCC; (ii) to measure GSTA1 mRNA expression in HCCs. For that purpose, we genotyped non-tumor-tissue-derived DNA from 48 HCC patients and white-blood-cell-derived DNA from 37 healthy individuals by restriction fragment length polymorphism (RFLP). In addition, expression of GSTA1 mRNA was assessed by real-time PCR in 18 matching pairs of HCCs and non-tumor livers. Survival analysis was performed on an annotated microarray dataset containing 247 HCC patients (GSE14520). The GSTA1 TT genotype was more frequent in HCC than in non-HCC patients (27% versus 5%, respectively), suggesting that individuals carrying this genotype could be associated with 2-fold higher risk of developing HCCs (odds ratio = 2.1; p = 0.02). Also, we found that GSTA1 mRNA expression was lower in HCCs than in non-tumor livers. HCCs expressing the highest GSTA1 mRNA levels were the smallest in size (R = -0.67; p = 0.007), expressed the highest levels of liver-enriched genes such as ALB (albumin, R = -0.67; p = 0.007) and COL18A1 (procollagen type XVIII, R = -0.50; p = 0.03) and showed the most favorable disease-free (OR = 0.54; p<0.001) and overall (OR = 0.56; p = 0.006) outcomes. Moreover, GSTA1 was found within a 263-gene network involved in well-differentiated hepatocyte functions. In conclusion, HCCs are characterized by two GSTA1 features: the TT SNP and reduced GSTA1 gene expression in a context of hepatocyte de-differentiation.
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