|Year : 2019 | Volume
| Issue : 4 | Page : 522-528
The prevalence of Helicobacter pylori cagA (+ve) among patients with gastric cancer: an Egyptian study
Ahmed N El Mazny1, Tarek Hishmat1, Ahmed Hussein1, Doaa Gaith2
1 Department of Internal Medicine, Division of Gastroenterology, Kasr Al Ainy Faculty of Medicine, Cairo University, Cairo, Egypt
2 Department of Clinical Pathology, Kasr Al Ainy Faculty of Medicine, Cairo University, Cairo, Egypt
|Date of Submission||23-Apr-2019|
|Date of Acceptance||30-May-2019|
|Date of Web Publication||18-Aug-2020|
MD Ahmed N El Mazny
Internal Medicine, 26, 1st Touristic Area, 6th October City, Cairo, 1256
Source of Support: None, Conflict of Interest: None
Introduction and aims Gastric cancer is currently the second most common cause of cancer-related death in the world and the fifth most common cancer and the fourth leading cause of cancer-related death in Europe. It has been evident for more than the past 20 years that Helicobacter pylori is involved in the development of gastric adenocarcinoma. The cagA gene of H. pylori is the main virulence factor that leads to the development of gastric adenocarcinoma through the derangement of cellular architecture and signaling. The objective of our work is to study the prevalence of cagA among patients with gastric cancer.
Patients and methods This descriptive study was done on 60 patients with gastric cancer underwent serum anti-H. pylori IgM and anti-cagA IgG assessment, computed tomography, upper endoscopy, and biopsy taking, and if needed, computed tomography-guided biopsy, followed by histopathological examination.
Results A total of 34 (56.67%) patients were cagA +ve and 26 (43.33%) patients were cagA −ve, with no statistically significant difference regarding sex or age.
Conclusion H. pylori cagA plays a significant role in development of gastric cancer, so we recommend not only H. pylori screening but also cagA virulence strain.
Keywords: cagA, gastric cancer, Helicobacter pylori, incidence of gastric cancer in eastern and western countries
|How to cite this article:|
El Mazny AN, Hishmat T, Hussein A, Gaith D. The prevalence of Helicobacter pylori cagA (+ve) among patients with gastric cancer: an Egyptian study. Egypt J Intern Med 2019;31:522-8
|How to cite this URL:|
El Mazny AN, Hishmat T, Hussein A, Gaith D. The prevalence of Helicobacter pylori cagA (+ve) among patients with gastric cancer: an Egyptian study. Egypt J Intern Med [serial online] 2019 [cited 2020 Sep 20];31:522-8. Available from: http://www.esim.eg.net/text.asp?2019/31/4/522/292245
| Introduction|| |
Gastric cancer is currently the second most common cause of cancer-related death in the world and the fifth most common cancer and the fourth leading cause of cancer-related death in Europe. In Egypt, the frequency of gastric cancer is 2% in males and 1.5% in females from the newly diagnosed cases, with patients’ median age being 54 years .
It has been evident for more than 20 years that Helicobacter pylori is involved in the development of gastric adenocarcinoma; in 1994, the WHO concluded that H. pylori is a definite or class I carcinogen in humans. H. pylori is responsible for ∼75% of all noncardiac gastric cancers and 63.4% of all stomach cancers worldwide .
A strain-specific H. pylori gene cagA (cytotoxin-associated gene A) is a component of the cag pathogenicity island. Several genes within this island encode products that are homologs of proteins of the type IV bacterial secretion pathway. The cagA gene of H. pylori is the main virulence factor that leads to the development of gastric adenocarcinoma through the derangement of cellular architecture and signaling .
The cag cytotoxin-associated gene pathogenicity island (cag PAI) plays an important role in H. pylori pathogenesis and is not expressed in all strains. Approximately 60% of H. pylori strains isolated in Western countries carry the cag PAI, whereas almost all of the East Asian strains isolated are cag PAI positive .
Therefore, the aim of this study is to determine the prevalence of cagA virulence factor in patients with gastric cancer infected with H. pylori, to examine the association of cagA virulence factor of H. pylori with gastric cancer, and to prove the increased incidence of gastric cancer in patients infected with H. pylori strains that have cagA virulence factor.
| Patients and methods|| |
This study was conducted in Internal Medicine Department, Kasr El Ainy Hospital and National Cancer Institute, Cairo University, between January 2017 and October 2018, in patients of age group 22–78 years old. There were 30 males and 30 females. This paper based on a study done in Kasr-Al Ainy for fulfillment of master degree in internal medicine (Kept in records of the Ethical committee files in Cairo University). All the participants are of Egyptian origin. Written consent was taken from each participant or a responsible family member after fully explaining the possible complications of the diagnostic procedures.
Our study aimed to determine the prevalence of cagA H. pylori antigen in patients with gastric cancer.
The following were the inclusion criteria:
- Age group must not be less than 18 years old.
- All patients must have a histologically and/or cytological confirmed diagnosis of gastric cancer.
- All patients with positive anti-H. pylori IgM.
- All patients have a performance status of ECOG scale less than or equal to 2 with life expectancy of at least 6 months.
- All patients should have compliance, mental state, and geographic proximity that allow adequate follow-up, and they have to provide written informed consent before any study-specific procedure.
The following patients were excluded:
- Pregnant and breastfeeding patients.
- Patients with a currently active second malignancy.
All patients were subjected to the following: full history taking, complete clinical examination, laboratory investigations, and H. pylori workup.
All serum samples obtained from patients with gastric cancer will be tested to detect anti-H. pylori IgM and anti-cagA IgG.
The serum samples were stored at −80°C until serological testing, which was performed using H. pylori line IgA/IgG immunoblot GB, (Druckdatum, Germany), according to the manufacturer’s instructions.
Pathogen antigen proteins are transferred into a nitrocellulose membrane by a special spraying process. The nitrocellulose membrane is then cut up into individual strips. Incubation of the antigen-coated nitrocellulose strips with samples of human serum or plasma permits the detection of specific antibodies. These antibodies develop immune complexes with the antigen fixed on the test strip. After removing the unbound antibodies by washing steps, the single nitrocellulose-strips are incubated with alkaline phosphatase-conjugated anti-human IgG or IgA antibodies, correspondingly. After unbound conjugated antibodies have been removed by a further washing step, visualization of the antigen-antibody complex (of the bound antibodies) is accomplished by the addition of a noncolored substrate, which forms blue-violet precipitates at each site (antigen bands) where the conjugated anti-human antibodies have bound. Depending on the observed band pattern, one can interpret the presence of specific IgG or IgA antibodies, correspondingly.
Data were analyzed using Statistical Program for Social Science (SPSS) version 18.0. Quantitative data were expressed as mean±standard deviation (SD). Qualitative data were expressed as frequency and percentage. (SPSS Statistics is a software package used for interactive, or batched, statistical analysis. Long produced by SPSS Inc., it was acquired by IBM (USA) in 2009.
| Results|| |
This is a descriptive study on 60 patients with gastric cancer who were diagnosed in National Cancer Institute, Cairo University, at the age group of 22–78 years old with mean age of 54.47 years. There were 30 males and 30 females ([Table 1],[Table 2],[Table 3],[Table 4]).
|Table 4 Comparison between cagA IgG (positive and negative) regarding demographic data|
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[Table 5] shows statistically significant difference between groups regarding complaints.
|Table 5 Comparison between cagA IgG (positive and negative) regarding anti-Helicobacter pylori IgM|
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[Table 6] and [Table 7] show statistically significant difference between groups regarding anti-H. pylori IgM ([Figure 1] and [Figure 2]).
|Table 6 The frequency and percentage of CT abdomen and pelvis findings in relation to cagA +ve|
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|Table 7 The frequency and percentage pathological findings in relation to cagA +ve|
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|Figure 1 The frequency and percentage of computed tomography abdomen and pelvis findings in relation to cagA +ve, with mural thickening of gastric wall having the highest percentage (14.07%) followed by pyloric mass (8.82%).|
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|Figure 2 The frequency and percentage of pathological findings in relation to cagA +ve, with adenocarcinoma grade 2 having the highest percentage (44.12%) followed by adenocarcinoma grade 3 (20.59%).|
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| Discussion|| |
It has been evident for more than 20 years that H. pylori is involved in the development of gastric adenocarcinoma; in 1994, the WHO concluded that H. pylori is a definite or class I carcinogen in humans. H. pylori is responsible for approximately 75% of all noncardia gastric cancers and 63.4% of all stomach cancers worldwide. The cagA gene of H. pylori is the main virulence factor that leads to the development of gastric adenocarcinoma through the derangement of cellular architecture and signaling ,.
In Egypt, a high prevalence of H. pylori infections has been reported, ranging from 70 up to 88% in the general population .
So, the aim of this study is to determine the prevalence of cagA virulence factor in patients with gastric cancer infected with H. pylori, to examine the association of cagA virulence factor of H. pylori with gastric cancer, and to prove the increased incidence of gastric cancer in patients infected with H. pylori strains that have cagA virulence factor.
In our study, we included 60 Egyptian patients proved to have gastric carcinoma and also infected with H. pylori.
The present study showed that the age range was 22–78 years old, with mean±SD of 54.47±12.78 years. This age group was approximately near to the age group of a study done by Liu et al. , which was done on patients with gastric cancer, where the age range, 33–83 years.
Our study found that 34 (56.67%) patients are cagA +ve and 26 (43.33%) patients are cagA −ve, with no statistically significant difference regarding sex or age. These results are in agreement with the results of a study done by Meine et al. , which was conducted on 29 patients with gastric cancer and showed that 62.1% of patients were infected by cagA-positive H. pylori, with no statistically significant difference regarding sex.
The current study showed that 35.29% (12 patients) of the patients complained of epigastric pain, which represents the highest percentage of all complaints, followed by recurrent vomiting (23.53%, eight patients) and then hematemesis (17.65%, six patients) in cagA +ve patients. These results are in agreement with a study done by Güdücüoğlu et al. , which was done on 99 H. pylori-infected patients with gastric cancer, complaining of epigastric pain, and the results showed that the positivity rates for H. pylori cagA was 78%, which is a higher percentage than our results.
It is encouraging to compare this result with that found by Erzin et al.  who concluded that the prevalence of cagA was 73.6% in their study done on 33 gastric cancer and H. pylori-infected patients complaining of dyspepsia.
Moreover, our results are in agreement with the study done by Said Essa et al.  on 99 H. pylori-infected patients, including 90 dyspeptic patients (30 each with gastric cancer, peptic ulcer, and nonulcer dyspepsia) and nine nondyspeptic healthy controls. They concluded that anti-cagA antibodies were more prevalent among dyspeptic patients with gastric cancer or peptic ulcer (73.3%) compared with those with nonulcer dyspepsia (40%).
The current study also found a statistically significant difference between cagA +ve and −ve patients regarding anti-H. pylori IgM titer, with range of 1.30–4.20 and mean±SD of 2.81±0.82 for +ve patients and range of 1.50–3.20 and mean±SD of 2.20±0.57 for −ve patients, with P value of 0.002.
This is against the study done by Suzuki and colleagues , which reported that the risk of gastric cancer is different between high and low cagA antibody titers. They examined 299 patients with gastric cancer and 1048 matched controls. Among seropositive patients for H. pylori antibody, those with low cagA antibody titers had higher and more significant risk [relative risk (RR), 3.9; P<0.001) for future gastric cancer than those with cagA seronegativity (RR, 2.2; P=0.0052) or high cagA antibody titers (RR, 2.0; P=0.0022) .
The current study observed that in upper endoscopic findings, pyloric mass has the highest percentage (16.2%) followed by mass at the greater curvature and fundal ulcer (10.8% each) in cagA +ve patients. These results are concordant with the study conducted by Peleteiro et al. , which was done on 41 cardia and 339 noncardia cancer cases undergoing gastrectomy and 380 community controls. The associations between H. pylori infection and cardia and noncardia cancers were further compared. No positive relation was found for H. pylori infection, but cagA-positive strains were associated with an increased risk of noncardia cancer (odds ratio=1.60, 95% confidence interval=1.17–2.18).
Moreover, this matched with the study done by Suzuki and colleagues, which reported that the risk of gastric cancer is different between high and low cagA antibody titers. They examined 299 noncardia gastric cancers and 1048 matched controls. Among seropositive patients for H. pylori antibody, those with positive cagA antibody had higher and more significant risk (RR, 3.9; P<0.001) for future noncardia gastric cancer than those with cagA seronegativity (RR, 2.2; P=0.0052) .These results are also in acceptance with the study done by Filipec Kanizaj T and colleagues , which was done on 30 patients with gastric adenocarcinoma .Upper gastrointestinal endoscopy was performed, and 4 mucosal biopsy samples were obtained and assessed according to updated Sydney protocol. CagA seropositivity was significantly more often present in patients with higher activity grade in the antrum (P=0.025), and this proves that cagA is linked with pathogenesis of pyloric masses in gastric cancer .
In contrast to our study, Ren and colleagues  performed a study on 196 gastric cardia cancer cases, and the rate of cagA positivity was 82.1%, indicating an association between cagA and gastric cardia cancer .
| Conclusion|| |
This study suggests that cagA plays a significant role in the development of gastric cancer in patients who were infected by H. pylori and can be used as a screening marker for early detection of gastric cancer.
So we recommend that cagA should be used in any patient with symptoms and signs related to H. pylori infection as screening marker for early detection of gastric cancer and for regular follow-up of H. pylori-infected patients.
All authors acknowledge their gratitude to the staff members of in-patient of Internal Medicine Department and National Cancer Institute for their help and support.
Work was done in Internal Medicine Department of Kasr Al Ainy Hospital, National Cancer Institute, Cairo University.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]