Effects of Genetic Polymorphisms of Glutathione S-transferase P1 on Helicobacter pylori-associated Gastric Cancer

Abstract

Background/Aims: Glutathione S-transferase P1 (GSTP1) scavenges radicals via its peroxidase activity. The purpose of this study was to determine the association of GSTP1 genetic polymorphisms with the expression of H. pylori-associated gastroduodenal disease. Methods: This study involved 1,911 subjects, comprising patients with four diseases (gastric cancer, dysplasia, benign gastric ulcer, and duodenal ulcer disease) and controls. Biallelic polymorphisms were genotyped by restriction fragment length polymorphism techniques. Results: The frequency of the genetic polymorphism at nucleotide 313 of GSTP1 did not differ among the five study groups. However, when the gastric cancer group was subdivided into advanced gastric cancer (AGC) and early gastric cancer, the frequency of the G/G genotype was significantly higher in the AGC group than in all the control subgroups (OR: 1.2, 95% CI: 1.1-4.9). The frequency of this genotype differed significantly in the H. pylori-positive AGC group (OR: 2.7, 95% CI: 1.1-6.3) but not in the H. pylori-negative group. Furthermore, the difference was greater in the intestinal type, and was not found in diffuse types of disease. Conclusions: This study found that genetic polymorphisms of GSTP1 were associated with H. pylori-associated gastric cancer only during the advanced stage of gastric cancer, with intestinal-type histology evident in H. pylori-positive subjects. (Gut and Liver 2008;2:23-29)

Allele and genotype frequencies of CYP3A4, CYP3A5, CYP3A7, and GSTP1 gene polymorphisms among mainland Tibetan, Mongolian, Uyghur, and Han Chinese populations

“…The allele frequencies of all four Chinese populations were significantly lower than that of African populations (all p < 0.0001, S6). [31][32][33][34][35][36][37] Among the four mainland Chinese populations, the allele was more frequent in the Uyghur population (0.25) than in the Tibetan (0.173, p = 0.006) or Han (0.188, p = 0.041) population (Tables 1 and 2)…”

Antioxidant-Rich Diet, GSTP1 rs1871042 Polymorphism, and Gastric Cancer Risk in a Hospital-Based Case-Control Study

“…In addition to the role of GSTP1 gene, the specific allele of GSTP1 is able to regulate oxidative stress and detoxification against carcinogenesis ( 21 , 65 ). Moreover, the impact of H. pylori infection on the relationship between GSTP1 genetic polymorphisms and GC risk varies, suggesting that H. pylori infection may have different oncogenic effects depending on GSTP1 genetic polymorphism, including controlling the activation of the detoxification system, thereby resulting in gastric carcinogenesis ( 36 , 77 ). A high intake of dietary ORAC may synergistically interact with GSTP1 rs1871042 polymorphism by detoxifying and eradicating excessive ROS, eventually leading to protection against the development of GC.…”

Antioxidant-rich diet, GSTP1 rs1871042 polymorphism, and gastric cancer risk in a hospital-based case-control study

“…within addition to the role of the GSTP1 gene, the speci c allele of GSTP1 is able to regulate oxidative stress and detoxi cation against carcinogenesis (21,58). Moreover, the impact of H. pylori infection on GSTP1 genetic polymorphisms regarding GC risk varies, suggesting that H. pylori infection may have different oncogenic effects, including controlling the activation of the detoxi cation system, resulting in gastric carcinogenesis, that depend on the GSTP1 genetic polymorphism (36,70). High intake of dietary ORAC may synergistically interact with the GSTP1 rs1871042 polymorphism by detoxifying and eradicating excessive ROS, eventually leading to protection against the development of GC.…”