Dataset Information

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.

SUBMITTER: Kang JM

PROVIDER: S-EPMC2871579 | biostudies-literature | 2008 Jun

REPOSITORIES: biostudies-literature

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Publications

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

Kang Jung Mook JM Kim Nayoung N Cho Sung-Il SI Lee Dong Ho DH Park Young Soo YS Kim Yu Rim YR Park Ji Hyun JH Lee Mi Kyoung MK Kim Joo Sung JS Jung Hyun Chae HC Song In Sung IS

Gut and liver 20080630 1

<h4>Background/aims</h4>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.<h4>Methods</h4>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 restricti ...[more]

PMID: 20485607

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Project description:BackgroundAnti-tuberculosis drug-induced hepatotoxicity (ATDH) is one of the most common adverse effects associated with tuberculosis (TB) therapy. Animal studies have demonstrated important roles of glutathione S-transferases in the prevention of chemical-induced hepatotoxicity. The aim of this study was to investigate the relationship between single nucleotide polymorphisms (SNPs) of glutathione S-transferase P1 (GSTP1) and ATDH in TB patients.MethodsWe used two independent samples for this genetic association study. In the initial prospective study, 322 newly diagnosed TB patients were followed up for three months after initiating anti-TB therapy. In an independent retrospective study, 115 ATDH patients and 116 patients without ATDH were selected to verify the results of the prospective study. Tag-SNPs of GSTP1 were genotyped either with the MassARRAY platform or the improved multiple ligase detection reaction (iMLDR) method. The associations between SNPs and ATDH were analyzed by logistic regression analysis adjusting for confounding factors.ResultsOf the 322 patients recruited in the prospective cohort, 35 were excluded during the 3 months of follow-up, and 30 were diagnosed with ATDH and were considered as the ATDH group. The remaining 257 subjects without ATDH were considered as the non-ATDH group. After correction for potential confounding factors, significant differences were found for rs1695 (A>G) under an allelic model (OR = 3.876, 95%CI: 1.258011.905; P = 0.018). In the retrospective study, rs1695 allele A also had a higher risk of ATDH (OR = 2.10, 95%CI: 1.17-3.76; P = 0.012). We only found rs4147581AA genotype under a dominant model was related to ATDH in the prospective study (OR = 2.578, 95%CI: 1.076-6.173; P = 0.034).ConclusionsThis is the first study to suggest that GSTP1 genotyping can be an important tool for identifying patients who are susceptible to ATDH. This result should be verified in independent large sample studies and also in other ethnic populations.

Project description:ObjectiveBoth variations in the interleukin-10 (IL10) gene and environmental factors are thought to influence inflammation and gastric carcinogenesis. Therefore, we investigated the associations between IL10 polymorphisms, Helicobacter pylori (H. pylori) infection, and smoking in noncardia gastric carcinogenesis in Koreans.MethodsWe genotyped three promoter polymorphisms (-1082A>G, -819T>C, and -592 A>C) of IL10 in a case-control study of 495 noncardia gastric cancer patients and 495 sex- and age-matched healthy controls. Multiple logistic regression models were used to detect the effects of IL10 polymorphisms, H. pylori infection, and smoking on the risk of gastric cancer, which was stratified by the histological type of gastric cancer.ResultsThe IL10-819C and -592C alleles were found to have complete linkage disequilibrium, and all three IL10 polymorphisms were associated with an increased risk of intestinal-type noncardia gastric cancer. These associations were observed only in H. pylori-positive subjects and current smokers. A statistically significant interaction between the IL10-592 genotype and H. pylori infection on the risk of intestinal-type gastric cancer was observed (P for interaction = 0.047). In addition, H. pylori-positive smokers who were carriers of either the IL10-1082G (OR [95% CI] = 17.76 [6.17-51.06]) or the -592C (OR [95% CI] = 8.37 [2.79-25.16]) allele had an increased risk of intestinal-type gastric cancer compared to H. pylori-negative nonsmokers homozygous for IL10-1082A and -592A, respectively. The interaction between the IL10-1082 polymorphism and the combined effects of H. pylori infection and smoking tended towards significance (P for interaction = 0.080).ConclusionsInflammation-related genetic variants may interact with H. pylori infection and smoking to increase the risk of noncardia gastric cancer, particularly the intestinal-type. These findings may be helpful in identifying individuals at an increased risk for developing noncardia gastric cancer.

Dataset Information

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

Background/aims

Methods

Results

Conclusions

Publications

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

Similar Datasets

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