Article Abstract

GSTM1 and GSTT1 copy number variants and the risk to Thai females of hepatocellular carcinoma

Authors: Thanet Sophonnithiprasert, Pensri Saelee, Tanett Pongtheerat


Background: Hepatocellular carcinoma (HCC) is a common malignancy found throughout the world that most often occurs in males. The cancer is associated with many risk factors such as viral infection, cirrhosis, alcohol, smoking, and fungal toxins. GSTM1 and GSTT1 are detoxification enzymes activated by the cleansing of carcinogenic compounds. Low DNA copy numbers of Glutathione S-transferases M1 and T1 result in a loss of enzyme activity, which causes carcinogenesis factors. DNA copy number variants (CNVs) were determined to compare the differences between the frequencies of GSTM1 and GSTT1 in a control group and patients. Then, the association of these genes with the pathological/survival status of HCC patients was investigated.
Methods: Forty-nine Thai HCC patients’ DNA and the genomic DNA of 66 healthy controls were investigated for GSTM1 and GSTT1 CNVs by real-time polymerase chain reaction (PCR). Then, the correlations between GSTM1 and GSTT1 patients’ CNVs, the control group, and clinico-pathological parameters were determined.
Results: The results show that were no differences between the CNVs of GSTM1 and GSTT1 in the controls and patients (P≥0.05). Only GSTT1 genotypes 0/0 correlated to an increase in the risk of hepatocellular carcinogenesis (OR value was 1.88). GSTM1 CNVs were associated with the gender of patients (P=0.002). However, no correlations were found between GSTT1 CNVs and any of the clinico-pathological parameters.
Conclusions: The results suggest that only GSTT1 CNVs are associated with increased risk factors of HCC in Thais. GSTM1 copy numbers had a dominant correlation with female HCC patients.