Abstract
BackgroundHepatocellular carcinoma (HCC) is one of the most frequent malignant neoplasms in the world. Genetic polymorphism has been reported to be a factor increasing the risk of HCC. Phase II enzymes such as glutathione s-transferases (GSTP1, GSTA1) play important roles in protecting cells against damage induced by carcinogens. The aim of this study was to estimate the relationship of the GSTP1 and GSTA1 gene polymorphisms to HCC risk and clinico-pathological status.MethodsPolymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to measure GSTP1 (A→G) and GSTA1 (C→T) gene polymorphisms in 386 healthy controls and 177 patients with HCC.ResultsNeither gene polymorphism was associated with the clinico-pathological status of HCC and serum expression of liver-related clinico-pathological markers. No association between the GSTA1 gene polymorphism and HCC susceptibility was found. However, in the younger group, aged ≤ 57 years, individuals with AG or GG alleles of GSTP1 had a 2.18-fold (95%CI = 1.09-4.36; p = 0.02) and 5.64-fold (95%CI = 1.02-31.18; p = 0.04) risk, respectively, of developing HCC compared to individuals with AA alleles, after adjusting for other confounders.ConclusionAG and GG alleles of GSTP1 gene polymorphisms may be considered as factors increasing the susceptibility to and risk of HCC in Taiwanese aged ≤ 57 years.
Highlights
Hepatocellular carcinoma (HCC) is one of the most frequent malignant neoplasms in the world
Except for age (p < 0.0001), there was a non-significant difference in distribution of gender, race, ethnic group, residential area, and genetic polymorphisms between the HCC patients and healthy controls, even when we further classified the individuals with at least one mutated allele as one subgroup and regarded the individuals with homozygous wild type alleles as another subgroup to estimate the adjusted odds ratios (AORs) with their 95% confidence intervals (CIs), or combined different genetic distributions for estimating the interaction effect between the GSTP1 and GSTA1 gene polymorphisms on the susceptibility to HCC (Table 1)
In the younger group, aged ≤ 57 years, individuals with AG or GG alleles of GSTP1 had a 2.18-fold risk and 5.64-fold risk, respectively, of developing HCC compared to individuals with AA alleles, after adjustment for other confounders, but no association was found in the older group, aged > 57 years (Table 2)
Summary
Hepatocellular carcinoma (HCC) is one of the most frequent malignant neoplasms in the world. Phase II enzymes such as glutathione s-transferases (GSTP1, GSTA1) play important roles in protecting cells against damage induced by carcinogens. Phase II enzymes such as glutathione s-transferases (GSTP1, GSTA1) have been suggested to play an important role in protecting cells against damage induced by carcinogens, through regulation of the conjugation of a wide range of xenobiotics for excretion of hydrophilic metabolites [4,5,6]. Up-expression of GSTA was suggested to protect liver cells against oxidative stress [17,18] via an extracellular signal-regulated kinases (ERKs) and p38 kinase (p38K)-related pathway [18], as well as through the inhibition of H2O2-induced apoptosis to inhibit reactive oxygen species (ROS)induced lipid peroxidation [17]
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