We conclude that the studied polymorphisms affecting GSTP1, GSTA1 and GSTM3 genes are probably not related to the risk of developing hepatocellular carcinoma in the studied population.
Moreover, the effects of OCPs exposure on HCC risk are more pronounced amongst GSTP1 (Ile/Val + Val/Val) and GSTP1 promoter methylation subjects than those who were GSTP1 (Ile/Ile) and unmethylated subjects.
Two SNPs (GSTO2: rs7085725 and GSTP1: rs4147581) were significantly associated with overall survival in HCC patients (P = 0.035 and 0.042, respectively).
During the pathogenesis of human hepatocellular carcinoma (HCC), the CpG island encompassing the pi-class glutathione S-transferase gene (GSTP1) becomes hypermethylated.
AG and GG alleles of GSTP1 gene polymorphisms may be considered as factors increasing the susceptibility to and risk of HCC in Taiwanese aged < or = 57 years.
In conclusion, the meta-analysis suggests that there is little evidence for the association between GSTP1Ile105Val polymorphism and hepatocellular carcinoma risk.
We conclude that the studied polymorphisms affecting GSTP1, GSTA1 and GSTM3 genes are probably not related to the risk of developing hepatocellular carcinoma in the studied population.
The hypermethylated status of the promoter regions of p16INK4a, RASSF1A, E cadherin, and GSTP1 was observed in 10 (40%), 14 (56%), 6 (24%), and 12 (48%) of 25 patients with hepatocellular carcinoma, respectively.
These data indicate that the epigenetic aberrance of promoter CpG island hypermethylation of the GSTP1 gene may contribute to the hepatopathogenesis of HCC and is a potential valuable biomarker for noninvasive disease monitoring and HCC early diagnosis.
GSTP1 is a largely investigated tissue biomarker in several malignancies such as prostate, breast, lung and hepatocellular carcinoma with good performances especially for diagnostic purposes.
Under abnormal conditions the excessive reactive oxygen species generation results in genetic predisposition of various genes (as ADH, ALDH, CYP2E1, GSTT1, GSTP1 and GSTM1) involved in xenobiotic metabolic pathways, associated with susceptibility to different liver related diseases such as fibrosis, cirrhosis and hepatocellular carcinoma.
In contrast, levels of transcript were significantly elevated (up to 16-fold) in total RNA derived from bladder and ureteric carcinomas, with the highest levels of elevation approaching those previously found only for the GST-P gene in experimentally induced rodent hepatocellular carcinomas.
The methylation frequencies of the ten genes examined in HCC were 40.0% for p14 ( ARF ), 60.9% for p15 ( INK4b ), 70.4% for p16 ( INK4a ), 34.8% for p73, 70.4% for GSTP1, 64.3% for MGMT, 13.0% for hMLH1, 59.1% for RARbeta, 82.6% for SOCS-1, and 80.9% for OPCML.
Highly metastatic hepatocellular carcinomas induced in male F344 rats treated with N-nitrosomorpholine in combination with other hepatocarcinogens show a high incidence of p53 gene mutations along with altered mRNA expression of tumor-related genes.
Our meta-analysis suggested strong associations between APC, GSTP1 and SOCS1 gene promoter methylation and the risk of HCC, suggesting these to be promising biomarkers for HCC.
In conclusion, hypermethylation of some specific, but not all, tumor associated genes may be involved in hepatocarcinogenesis; examination of the methylation status of E-cadherin, GSTP1, P16, and RASSF1A in the plasma samples might have limited usage for HCC diagnosis.