Association of polymorphisms in myeloperoxidase and catalase genes with precancerous changes in the gastric mucosa of patients at inner-city hospitals in New York

Abstract

Gastric carcinogenesis is a multistep process progressing from chronic gastritis, through glandular atrophy (GA), intestinal metaplasia (IM) and dysplasia. We have previously demonstrated that minority patients at New York City hospitals are infected with a relatively virulent strain of H. pylori (Hp) and that Hp infection is associated with an increased incidence of precancerous changes in the gastric mucosa. Nevertheless, precancerous changes are not observed in every Hp-infected individual, suggesting that environmental and genetic factors may also play a role in the formation and appearance of precancerous lesions. In the present study, the association between polymorphisms in the promoter regions of human myeloperoxidase (MPO-463G¨A) and catalase (CAT-262C¨T) genes and the appearance of precancerous changes in the gastric mucosa of our patient population were examined. Patients enrolled in this study were undergoing endoscopy for gastrointestinal complaints. Samples were collected from 126 patients at Kings County Hospital in Brooklyn and St. John's Episcopal Hospital in Queens. One antral biopsy was taken for genotyping, while additional biopsies were taken from the antrum and fundic region for histological analysis and were scored with respect to acute and chronic inflammation, GA, IM and Hp infestation according to the Sydney classification. MPO and CAT genotypes were determined by PCR and RFLP. CAT genotypes did not influence the incidence or severity of precancerous lesions in the fundic or antral regions of the stomach, whereas the MPO-463A allele was associated with an increase in intensity of gastric atrophy in the fundic mucosa. In Hp-infected individuals, the MPO-463G/G genotype was associated with an increase in the incidence of IM in the antrum, whereas the A allele was associated with an increase in IM in the fundic region. These paradoxical findings suggest that different MPO genotypes are associated with the appearance of IM in distinct anatomical regions of the stomach. However, since the majority of gastric cancer (GC) cases in our patient population occurred in the antrum, the MPO-463G/G genotype, which is associated with increased MPO expression and antral IM, may be considered a risk factor for GC.

The CAT-262 C>T, MnSOD Ala16Val, GPX1 Pro198Leu Polymorphisms Related to Oxidative Stress and the Presence of Gastric Lesions

“…On the other hand, our previous works showed different influence of various genetic factors on gastroduodenal diseases in comparison with those reported in other populations [24,25]. For studying the CAT-262C>T, GPX1 Pro198Leu, MnSOD Ala16Val polymorphism in relation to endoscopic and histologic gastric lesions occurrence [26][27][28] we investigated the impact of variants of the mentioned SNPs and environmental factors (drug consumptions, alcohol and smoking habits) on endoscopic gastro-duodenal lesions and gastric histological changes in one single multivariable model.…”

Myeloperoxidase Immunohistochemistry as a Measure of Disease Activity in Ulcerative Colitis: Association With Ulcerative Colitis-Colorectal Cancer, Tumor Necrosis Factor Polymorphism and RUNX3 Methylation

“…27 Studies in ovarian and gastric cancer, also associated with inflammation, have shown a relationship between the A allele and decreased incidence of either cancer. 28,29 We screened a subset of the patients in the current study for this MPO polymorphism and found there was no significant difference between cases and controls (data not shown). A prior study in leukemia and myeloma demonstrated elevated levels of MPO in the serum of cancer patients versus controls.…”

Helicobacter pylori and cytokine gene variants as predictors of premalignant gastric lesions

“…A study of gene polymorphisms involved in oxidative stress (of CAT , MnSOD and GPX1 genes) in relation to premalignant gastric lesions demonstrated contradictory results in different populations[122-124], despite the accepted role of oxidative stress as a consequence of H. pylori being a contributing factor in gastric carcinogenesis[118]. The gene variants of glutathione S-transferases (GSTs) involved in the metabolism of carcinogens, drugs, and reactive oxygen species were shown to be involved in GC predisposition, but with discordant results[125].…”