Herein, we investigated the relationship of three GSTs polymorphisms (GSTT1 deletion, GSTM1 deletion, GSTP1 rs1695) as well as GSTP1 promoter region DNA methylation and HCC risk with a particular focus on the interaction with OCPs exposure among 90 HCC cases and 99 controls in a Chinese population.
In vitro, Transwell and doxorubicin (DOX)-induced apoptosis assays revealed that GSTM1 showed opposite functions in different HCC cell lines with varied TP53 genotype statuses.
The pooled analysis showed that both GSTM1 null genotypes (OR = 1.37, 95% CI = 1.18-1.59) and GSTT1 null genotypes (OR = 1.43, 95% CI = 1.23-1.66) increased the risk of HCC.
GSTM1 had the highest frequency for gene gain (45.45, 39.18, 31.01, and 34.77%, respectively) and for gene loss (18.18, 29.38, 20.89, and 26.68%, respectively) in DLBL, acute myeloid leukemia, liver hepatocellular carcinoma, and LUSC.
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.
We speculate that GSTM1 and GSTT1 genotype variations have their own independent function in HCC development and may mutate independently to cause HCC.
By pooling data from 10 studies (1,639 cases and 2,224 controls) that considered combinations of GSTT1 and GSTM1 genotypes, a statistically significant increased risk for HCC (odd ratio = 1.85, 95% CI 1.37–2.49) was detected for individuals with combined deletion mutations in both genes compared with positive genotypes.
Therefore, we performed an updated meta-analysis to clarify this inconsistency and to establish a comprehensive picture of the association of the polymorphisms of GSTM1 and GSTT1 with HCC susceptibility.
Additionally, this polymorphism multiplicatively interacted with the glutathione S-transferase M1 polymorphism with respect to HCC risk (ORinteraction = 2.13).
This meta-analysis suggests null genotypes of GSTM1 and GSTT1 are both associated with increased HCC risk in Asians, and individuals with the dual null genotype of GSTM1/GSTT1 are particularly susceptible to developing HCC.
We conducted a case-control study, including 209 incident cases with hepatocellular carcinoma (HCC) and two different control groups [275 hospital controls and 381 patients with chronic liver disease (CLD) without HCC], to investigate whether CYP1A1, CYP1A2, CYP2A6, CYP2E1, GSTM1 and NAT2 polymorphisms are related to the risk of HCC with any interaction with cigarette smoking.
The present study was undertaken to evaluate the association of GSTT1 and GSTM1 null genotypes and mEPHX polymorphisms with hepatitis virus-related HCC risk in an Indian population.
The present study was undertaken to evaluate the association of GSTT1 and GSTM1 null genotypes and mEPHX polymorphisms with hepatitis virus-related HCC risk in an Indian population.
On the contrary, no relationship was observed between UGT1A7 polymorphisms considered alone or in interaction with GSTM1 or XRCC1 polymorphisms and HCC.