The Interaction between GSTT1, GSTM1, and GSTP1 Ile105Val Gene Polymorphisms and Environmental Risk Factors in Premalignant Gastric Lesions Risk

The study investigated the possible influence of GSTM1, GSTT1, and GSTP1 gene polymorphisms as predisposing factors for premalignant gastric lesions as well as their interaction with H. pylori infection, gastrotoxic drugs, smoking, and alcohol consumption. In this study, 270 patients with a complet set of gastric biopsies and successfully genotyped were finally included. The GSTM1 gene polymorphism had significant contribution in mild/severe endoscopic lesions (p=0.01) as well as in premalignant lesions (p=0.01). The GSTM1 null genotype increased the risk for mucosal defects in H. pylori-negative patients (OR = 2.27, 95% CI: 1.20–4.37) and the risk for premalignant lesions in patients with no alcohol consumption (OR = 2.13, 95% CI: 1.19–3.83). The GSTT1 deleted polymorphism did not significantly increase the risk for premalignant lesions in the absence of gastrotoxic drugs (OR = 1.82, 95% CI: 0.72–4.74). The combined GSTT1T1 and GSTM1 null polymorphisms were borderline correlated with an increased risk for premalignant lesions (OR = 1.72, 95% CI: 1.00–2.97). The wild-type GSTP1 Ile/Ile genotype versus the variant genotypes Ile/Val + Val/Val was significantly associated with a decreased risk of gastric atrophy/intestinal metaplasia (OR = 0.60, 95% CI: 0.37–0.98). In conclusion, the GSTM1 and GSTT1 null genotypes increased the risk for premalignant and endoscopic gastric lesions, modulated by H. pylori, alcohol, or gastrotoxic drug consumption, while the presence of the GSTP1Val allele seemed to reduce the risk for premalignant lesions.

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Chronic Statin Therapy and Histologic Gastric Changes

Journal of Interdisciplinary Medicine ◽

10.2478/jim-2018-0039 ◽

2018 ◽

Vol 3 (4) ◽

pp. 221-224

Author(s):

Anca Negovan ◽

Ioan Țilea ◽

Septimiu Voidăzan ◽

Simona Mocan ◽

Andreea Szoke ◽

...

Keyword(s):

Alcohol Consumption ◽

Statin Therapy ◽

Statin Treatment ◽

Premalignant Lesions ◽

Gastric Lesions ◽

Ulcer Disease ◽

Biliary Reflux ◽

Increased Risk ◽

Glandular Atrophy ◽

H Pylori

Abstract Background: The additional benefits of certain frequently used chronic drugs such as statins or aspirin are investigated for their possible effect of influencing various types of cancer, including gastric cancer. The possible role of statins in the occurrence of pre-neoplastic gastric lesions has not been investigated. Aim: The study aims to determine the influence of chronic statin therapy on premalignant gastric lesions (glandular atrophy, intestinal metaplasia and dysplasia), adjusted with the most important aggressive environmental factors of the gastric mucosa (Helicobacter pylori [H. pylori] infection, low-dose aspirin [acetylsalicylic acid, ASA], biliary reflux, smoking, alcohol consumption). Method: The study included 566 patients with cardiovascular diseases who underwent an upper endoscopy: 222 patients with chronic statin therapy (atorvastatin 20–80 mg/day or rosuvastatin 5–20 mg/day for at least 6 months) and 344 patients without statin intake. A complete set of biopsies from the gastric antrum and corpus were routinely processed and examined, and demographical, clinical, and pathological variables were recorded. Results: Active H. pylori infection in gastric biopsies (p = 0.45), biliary reflux (p = 0.74), alcohol consumption (p = 0.43), or prior ulcer disease (p = 0.07; OR: 0.59; 95% CI: 0.33–1.04) were not associated with an increased risk for premalignant lesions, neither in the statin, nor the no-statin group. Smoking was associated with premalignant lesions in both groups (p = 0.01; OR: 2.24; 95% CI: 1.12–4.47; and p = 0.04; OR: 1.72; 95% CI: 1.01–2.94, respectively), while chronic use of ASA had no influence (p = 0.24, respective p = 0.35). In multivariate regression models, chronic treatment with statins had a protective effect (p = 0.006; OR: 0.59; 95% CI: 0.4–0.8), while smoking (p = 0.01; OR: 1.99; 95% CI: 1.17–3.39) and age >50 years (p <0.01, OR: 3.09; 95% CI: 1.84–5.21) were predictors for pre-neoplastic lesions. H. pylori infection, gender, alcohol consumption, biliary reflux, or prior ulcer disease were not associated with premalignant lesions (p >0.05). Conclusions: In the studied population, chronic statin treatment seems to be associated with a decreased risk for premalignant gastric lesions, while age over 50 years and smoking, regardless of gender or ASA consumption, remain the most important risk factors for premalignant gastric lesions.

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Genetic Polymorphisms of CXCL8 (−251) Are Associated with the Susceptibility of Helicobacter pylori Infection Increased the Risk of Inflammation and Gastric Cancer in Thai Gastroduodenal Patients

Iranian Journal of Allergy Asthma and Immunology ◽

10.18502/ijaai.v18i4.1417 ◽

2019 ◽

Cited By ~ 1

Author(s):

Wongwarut Boonyanugomol ◽

Kamolchanok Rukseree ◽

Worrarat Kongkasame ◽

Prasit Palittapongarnpim ◽

Seung-Chul Baik ◽

...

Keyword(s):

Gene Expression ◽

Gastric Cancer ◽

Helicobacter Pylori ◽

Cancer Progression ◽

Chemokine Receptor ◽

Gene Polymorphisms ◽

Inflammatory Responses ◽

Increased Risk ◽

Cxc Chemokine ◽

H Pylori

CXC Chemokine Ligand 8 (CXCL8) plays an important role in gastric inflammation and in the progression of gastric cancer induced by Helicobacter pylori (H. pylori) infection. The association of CXCL8, CXC Chemokine Receptor 1 (CXCR1), and CXC Chemokine Receptor 2 (CXCR2) polymorphisms with H. pylori infection and gastric cancer progression needs to be investigated in a population within an enigma area consisting of multiple ethnicities, such as Thailand. To analyze the relative risk of H. pylori infection and gastric cancer among Thai gastroduodenal patients, gene polymorphisms in CXCL8 (promoter region -251) and in CXCR1 and CXCR2 (receptors for CXCL8) were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele specific-PCR (AS-PCR). We also determined the presence of cytotoxin-associated gene A (cagA) in Thai patients with H. pylori infection. Correlation between the CXCL8 (-251) polymorphism and CXCL8 gene expression was evaluated by quantitative reverse transcriptase-PCR (qRT-PCR). We found a significant association between the T/A and A/A genotypes of CXCL8 (-251) with H. pylori infection. However, no significant correlation was found between the CXCR1 (+2607) and CXCR2 (+1208) gene polymorphisms with H. pylori infection among Thai gastroduodenal subjects. Within the H. pylori-infected group of Thai gastroduodenal patients, no significant differences in cagA were observed. In addition, the A/A genotype of CXCL8 (-251) significantly correlated with the risk of gastric cancer and correlated with higher CXCL8 gene expression levels in Thai gastroduodenal patients. These results suggest that CXCL8 (-251) polymorphisms are associated with H. pylori infection, an increased risk of stronger inflammatory responses, and gastric cancer in Thai gastroduodenal patients.

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Cytokine TGF-β1, TNF-α, IFN-γ and IL‐6 Gene Polymorphisms and Localization of Premalignant Gastric Lesions in Immunohistochemically H. pylori-negative Patients

International Journal of Medical Sciences ◽

10.7150/ijms.60517 ◽

2021 ◽

Vol 18 (12) ◽

pp. 2743-2751

Author(s):

Anca Negovan ◽

Mihaela Iancu ◽

Florin Tripon ◽

Andrei Crauciuc ◽

Simona Mocan ◽

...

Keyword(s):

Gene Polymorphisms ◽

Gastric Lesions ◽

Tnf Α ◽

Ifn Γ ◽

H Pylori ◽

Tgf Β1

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Precancerous Gastric Lesions with Helicobacter pylori vacA+/babA2+/oipA+ Genotype Increase the Risk of Gastric Cancer

BioMed Research International ◽

10.1155/2020/7243029 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Theeraya Simawaranon Bartpho ◽

Wareeporn Wattanawongdon ◽

Taweesak Tongtawee ◽

Chatchanok Paoin ◽

Kokiet Kangwantas ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Clinical Outcomes ◽

Chronic Gastritis ◽

Virulence Genes ◽

Gastric Lesions ◽

Precancerous Gastric Lesions ◽

Increased Risk ◽

H Pylori ◽

Gastric Cancer Patients

Objective. The clinical outcomes of gastric diseases such as chronic gastritis, peptic ulcer, and gastric cancer have been attributed to the interplay of virulence factors of Helicobacter pylori (H. pylori), host genetic susceptibility, and host immune responses. This study investigated the presence of cagA, vacA, iceA2, babA2, and oipA genes and their association with clinical outcomes. Methods. Chronic gastritis, atrophic gastritis, and intestinal metaplasia specimens were obtained from patients who underwent endoscopy and surgical resection between January 2017 and December 2018; specimens from gastric cancer patients treated between January 2014 and December 2018 were also added. H. pylori infection and virulence genes (cagA, vacA, iceA2, babA2, and oipA) were determined using real-time PCR. The association between H. pylori genotypes and clinical outcomes were evaluated using multivariate regression model analysis. The overall survival of gastric cancer patients was compared between genotype combinations. Results. H. pylori was positive in 166 patients with chronic gastritis, precancerous gastric lesions, and gastric cancer. The genes vacA, babA2, and oipA were most prevalent in chronic gastritis (73%), precancerous gastric lesions (62%), and gastric cancer (91%), respectively. The vacA, babA2, and oipA genes were associated with increased risk of gastric cancer (OR = 1.23; 95% CI = 1.13–3.32; P=0.033, OR = 2.64; 95% CI = 1.44–4.82, P=0.024, and OR = 2.79; 95% CI = 1.58–5.41; P=0.031, respectively). Interestingly, H. pylori vacA+/babA2+/oipA+ genotype infection was associated with increased risk of gastric cancer (OR = 3.85, 95% CI = 1.67–5.77, P=0.014). Conclusion. In this present study, we reported on the virulence genes of H. pylori infection to reveal their association with increased risk of chronic gastritis, precancerous gastric lesions, and gastric cancer. Precancerous gastric lesions with H. pylori vacA+/babA2+/oipA+ genotype increased the risk of gastric cancer.

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Association of Tumor Necrosis Factor Receptor 1 Promoter Gene Polymorphisms (-580 A/G and -609 G/T) and TNFR1 Serum Levels with the Susceptibility to Gastric Precancerous Lesions and Gastric Cancer Related to H. pylori Infection in a Moroccan Population

BioMed Research International ◽

10.1155/2020/2451854 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Ghizlane Bounder ◽

Mohamed R. Jouimyi ◽

Hasna Boura ◽

Hassan Jouhadi ◽

Wafaa Badre ◽

...

Keyword(s):

Gastric Cancer ◽

Gene Polymorphisms ◽

Precancerous Lesions ◽

Precancerous Lesion ◽

Tumor Necrosis Factor Receptor ◽

Serum Levels ◽

Recessive Model ◽

Gastric Lesions ◽

Promoter Gene ◽

H Pylori

Chronic inflammation due to H. pylori infection is the risk factor of gastric cancer (GC). Through its receptor (TNFR1), TNF-α plays a fundamental role in inflammatory, infectious, and tumor processes. Dysregulation of TNFR1 gene expression could impact many biological processes that can lead to cancer. This study is aimed at evaluating the association of TNFR1 promoter gene polymorphisms (-580 A/G and -609 G/T) and TNFR1 serum levels with GC and precancerous lesion susceptibility. Patients suffering from gastric lesions (65 chronic gastritis, 50 precancerous lesions, and 40 GC) related to H. pylori infection and 63 healthy controls (HC) were involved in this study. Individuals are genotyped by TNFR1 gene promoter sequencing, and TNFR1 serum levels were measured by the ELISA quantitative method. Concerning TNFR1 -609 G/T locus, we noticed that the T allele was associated with an attenuated susceptibility to GC (OR=0.4; p value = 0.02). At the genotypic level and under the recessive model, the TNFR1 -609 TT genotype showed a decreased risk of GC (OR=0.3, p value = 0.03) compared to the combined (GG/GT) genotypes. TNFR1 serum levels have been increased together with gastric lesion severity (p value < 0.05). The TNFR1 -609 TT genotype seemed linked to a low level of sTNFR1 compared to GT and GG genotypes (p value = 0.07). Concerning TNFR1 -580 A/G locus, no significant relation was noticed between this polymorphism and GC susceptibility, as well as with the TNFR1 serum level. Our results suggest that the TNFR1 -609 T allele appears to have a protective effect against GC. High levels of TNFR1 serum levels seemed to be associated with the aggressiveness of gastric lesions. Therefore, our results suggest that TNFR1 -609 T/G polymorphism and the TNFR1 serum levels may be related to GC susceptibility.

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Helicobacter Pylori and its Determinations on Gastric Biopsies

Acta Medica Marisiensis ◽

10.1515/amma-2015-0066 ◽

2015 ◽

Vol 61 (4) ◽

pp. 303-308

Author(s):

Fülöp Emöke ◽

Marcu Simona Tünde ◽

Borda Angela ◽

Voidăzan Septimiu ◽

EF Fülöp ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Medical Literature ◽

Cross Sectional Study ◽

Premalignant Lesions ◽

Infection Prevalence ◽

Gastric Lesions ◽

Cross Sectional ◽

Single Region ◽

Gastric Biopsies

AbstractBackground and Aims. Gastric cancer, because of its aggressive evolution and the high mortality associated with it, remains one of the most debated subjects in medical literature with Helicobacter pylori (HP) as a major risk factor. Chronic inflammation caused by HP infection represents the initial site of the predisposing and afterwards premalignant lesions for gastric carcinoma. The purpose of this study was to evaluate the prevalence of HP infection, of predisposing and premalignant lesions on gastric biopsies, as well as to identify the correlations between them.Material and method. A retrospective cross-sectional study was performed on gastric biopsies collected endoscopically from a single region, antrum or corpus, and from different regions, between January 2012 and July 2014. Incidence of HP infection, of predisposing and premalignant gastric lesions, the correlation of HP infection and these lesions, were evaluated.Results. HP infection was diagnosed in 32.81%. Predisposing and premalignant lesions were present in 53.64% of biopsies with most of them in the antrum. HP infection stands out for the under 50 yo group (p=0.001). No correlation between frequency of HP infection and predisposing and premalignant lesions was observed.Conclusions. Prevalence of HP infection in our study suggests that besides HP infection, other factors are also involved in gastric cancer development. Biopsies from different regions of the gastric mucosa do not offer extra information regarding HP infection prevalence but may be helpful in evaluating incidence and extension of predisposing and premalignant lesions.

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Association between VEGF-634G>C Gene Polymorphism with Gastric Premalignant Lesions and Serum VEGF Levels in Helicobacter pylori Gastritis Patients

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2018.266 ◽

2018 ◽

Vol 6 (8) ◽

pp. 1328-1334

Author(s):

Gontar Alamsyah Siregar ◽

Ida Parwati ◽

Tri Hanggono Achmad ◽

Yoni Fuadah Syukriani

Keyword(s):

Gene Polymorphism ◽

General Hospital ◽

Serum Levels ◽

Premalignant Lesions ◽

Rapid Urease Test ◽

Serum Samples ◽

Cross Sectional ◽

Increased Risk ◽

Urease Test ◽

H Pylori

AIM: To evaluate the association between VEGF-634G>C gene polymorphism with premalignant gastric lesions as well as the level of VEGF.METHODS: This cross-sectional study included patients with H. pylori gastritis at Haji Adam Malik General Hospital, Permata Bunda General Hospital, and Universitas Sumatera Utara Hospital, Medan, Indonesia. Detection of H. pylori infection was made using positive results of 14C-UBT, rapid urease test, and/or immunohistochemistry. Gastric premalignant lesion diagnosis was made when one or more of the following were present: chronic atrophic gastritis, intestinal metaplasia, or dysplasia. Real-time polymerase chain reaction (RT-PCR) was used to examine VEGF-634G>C gene polymorphism. Additionally, serum samples of patients with H. pylori gastritis were obtained to determine the level of circulating VEGF. Data were analysed using SPSS version 22.RESULTS: A total number of 87 patients with H. pylori gastritis were included in this study. Of all participants, 26 patients (29.9%) showed gastric premalignancy. There was a significant association between GG+GC genotype of VEGF-634G>C and gastric premalignant lesions (P = 0.003; OR (CI 95%) = 6.07 (1.88-41.71)). VEGF-634 G>C polymorphism also showed an association with VEGF serum levels (P = 0.005). Patients with the GG+GC genotype would be at risk of 3.16 times to have high VEGF levels compared to CC genotypes.CONCLUSION: VEGF-634G>C polymorphism, in particular, GG+GC genotype was associated with an increased risk of gastric premalignant transformation as well as having high VEGF levels in patients with H.pylori gastritis.

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Glutathione S-transferase gene polymorphisms and risk of nasal or colorectal polyposis

Bioscience Reports ◽

10.1042/bsr20181226 ◽

2019 ◽

Vol 39 (1) ◽

Author(s):

Yonglan Zhang ◽

Haichao Zhang ◽

Peng Lin ◽

Guimin Zhang

Keyword(s):

Gene Polymorphisms ◽

Meta Analysis ◽

P Value ◽

Glutathione S Transferase ◽

Case Control Studies ◽

Colorectal Polyposis ◽

Transferase Gene ◽

Online Databases ◽

Increased Risk ◽

Gstp1 Ile105val

Abstract We observed inconsistent conclusions regarding the genetic role of glutathione S-transferase gene polymorphisms, including glutathione S-transferase M1 (GSTM1), glutathione S-transferase T1 (GSTT1) present/null, and glutathione S-transferase pi (GSTP1) Ile105Val polymorphisms, in the susceptibility to nasal or colorectal polyposis (NP or CP). Thus, we aimed to perform a meta-analysis to comprehensively evaluate this association by applying Stata/SE software. After the heterogeneity assumption, Mantel–Haenszel statistics were used to obtain the odds ratio (OR), 95% confidence interval (95% CI) and P-value of the association test (PA). We obtained a total of 235 articles by searching online databases. After screening, ten eligible case–control studies were finally enrolled in our meta-analysis. For the meta-analysis of the GSTT1 gene under present versus null, we observed a decreased risk of NP [OR = 0.65; PA=0.018], but not CP. In addition, we did not detect any evident association between the GSTM1 present/null polymorphism and NP or CP risk. For the meta-analysis of the GSTP1 Ile105Val polymorphism, compared with controls, an increased risk of NP cases was detected under the models of Val versus Ile (OR = 1.36; PA=0.027), Ile/Val versus Ile/Ile (OR = 1.70; PA=0.011) and Ile/Val+Val/Val versus Ile/Ile (OR = 1.65; PA=0.010). In conclusion, the null genotype of the GSTT1 polymorphism may be linked to an increased susceptibility to NP, whereas the Ile/Val genotype of the GSTP1 Ile105Val polymorphism may be associated with a decreased risk of NP.

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The Association of Antioxidants Gene Polymorphisms (SOD2 Ala16Val, GPx1 Pro198Leu, GSTP1 Ile105Val, and Cat −21 A/T) and Risk of Type 2 Diabetes Mellitus

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2020.5397 ◽

2020 ◽

Vol 8 (A) ◽

pp. 781-786

Author(s):

Mutiara Indah Sari ◽

Siti Syarifah ◽

Milahayati Daulay ◽

Zaimah Z. Tala

Keyword(s):

Diabetes Mellitus ◽

Risk Factors ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Gene Polymorphisms ◽

Recessive Model ◽

Increased Risk ◽

Gstp1 Ile105val ◽

Cat Gene

BACKGROUND: Antioxidant gene polymorphism is one of the genetic risk factors associated with type 2 diabetes mellitus (T2DM) incidence. AIM: This study was to analyze the association of superoxide dismutase 2 (SOD2) Ala16VAl, glutathione peroxidase (GPx1) Pro198Leu, glutathione S-transferase Pi1 (GSTP1) Ile105Val, and Cat −21 A/T gene polymorphisms and risk of T2DM. METHODS: We genotyped deoxyribonucleic acid of 120 T2DM patients and 80 healthy control by polymerase chain reaction and restriction fragment length polymorphism method, using a specific restriction enzyme. RESULTS: This study showed that the Val/Val of SOD2 was significantly associated with an increased risk of T2DM compared to the Ala/Ala+Ala/Val (p = 0.011; odds ratio [OR] = 2.220; confidence interval [CI] = 1.234–3.992). The TT genotype of Cat gene was also significantly associated with an increased risk of T2DM compared to the AA genotype (p = 0.027; OR = 5.000; CI = 1.079–23.176) and TT genotype to the AA+AT genotype (p = 0,030; OR = 4.738; CI = 1.039–21.600). However, there was no difference in all genetic models of GPx1 Pro198Leu and GSTP1 Ile105Val gene polymorphisms (p > 0.05). CONCLUSION: This study indicates that the Val/Val under the recessive model of SOD2 gene also TT genotype under the co-dominant model of Cat gene and TT genotype under the recessive model of Cat gene were associated with risk factors for T2DM occurrence.

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Prevalence, Characteristics and Endoscopic Management of Gastric Premalignant Lesions in France

Digestive Diseases ◽

10.1159/000503748 ◽

2019 ◽

Vol 38 (4) ◽

pp. 286-292 ◽

Cited By ~ 2

Author(s):

Nicolas Chapelle ◽

Matthieu Péron ◽

Jean-François Mosnier ◽

Lucille Quénéhervé ◽

Emmanuel Coron ◽

...

Keyword(s):

Precancerous Lesions ◽

Real Life ◽

Premalignant Lesions ◽

Endoscopic Management ◽

Low Grade ◽

Upper Endoscopy ◽

Gastric Biopsies ◽

H Pylori ◽

Histological Results

Introduction: Surveillance of gastric precancerous lesions (GPL) is recommended, but the data on their clinical and endoscopic management in a “real-life” practice are limited. Our aim was to study the modalities of endoscopic management of patients with GPL in France. Design: All the patients diagnosed with GPL in our center between 2000 and 2015 were grouped and analyzed according to the most severe GPL found, in the following order: atrophic gastritis only (AG), intestinal metaplasia (IM), low grade dysplasia (LGD), high grade dysplasia (HGD). Results: Out of 16,764 patients having undergone upper endoscopy with gastric biopsies, 507 were identified with GPL (detection rate 3.2%). Overall, Helicobacter pylori infection was found in 41% of patients. IM was by far the most frequently found lesion (79%), followed by LGD (17%), HGD (2%), and AG only (2%). H. pylori infection rate was decreasing, while the age of the patients was increasing, together with the increasing severity of GPL (p = 0.005). Only 28% of the patients had at least one follow-up endoscopy. No correlation was found between the endoscopist’s appreciation of the mucosa and histological results. Conclusion: In France, GPL can be expected in about 3% of patients undergoing upper endoscopy with gastric biopsies for any reason. The correlation between the endoscopic evaluation and histology is poor. Spreading of published guidelines should improve the management of patients with GPL in the future.

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