Anti CagA antibody among patients with non-cardia gastric cancer in comparison with non-ulcer dyspepsia in an area with high incidence of gastric cancer.

Abstract

To evaluate the correlation between anti CagA antibody (Ab) and presence of gastric cancer.
In a descriptive cross-sectional study during October 2003 to October 2005, in the Gastrointestinal Subspeciality Center in Razi Hospital, Rasht, Iran, we assessed anti-Helicobacter Ab immunoglobulin G (IgG) and anti CagA Ab IgG by the enzyme-linked immunosorbent assay (ELISA) method in 52 patients with gastric adenocarcinoma and 57 patients with nonulceric dyspepsia (NUD).
Among 52 patients with gastric cancer, anti-Helicobacter pylori Ab was negative in 13 (25%) and positive in 39 persons (75%). Among 57 patients with NUD, anti-Helicobacter pylori Ab was negative in 5 (8.5%) and positive in 52 patients (91.2%) (p=0.043). This significant difference did not remain after logistic regression for adjustment of confounders (p=0.068). The CagA Ab was positive in 22 (42.3%) patients with cancer and 32 (56.1%) of the NUD group. There was no difference in this regard before (p=0.212) and after (p=0.131) logistic regression analysis.
Anti CagA Ab does not have a significant value as an independent predictive factor in gastric adenocarcinoma.

Full text

Page 1

Anti CagA antibody among patients with non-cardia
gastric cancer in comparison with non-ulcer dyspepsia in
an area with high incidence of gastric cancer
Fariborz Mansour-Ghanaei, MD, Roxana Abbasi, MD, Farahnaz Joukar, MS, Sepiedeh Besharati, MD,
Neda Askari-Jirhandeh, MD.
1606
ABSTRACT
)Ab( رثختلل ةداضلما ماسجلأا ينب ةقلاعلا مييقت :فادهلأا
.ةدعلما ناطرس روضحو
ةيوعلما ضارملأا زكرم يف ةيضرع ةيفصو ةسارد تيرجأ :ةقيرطلا
ينب ام ةرتفلا للاخ ،ناريإ - تشار - يزارلا ىفشتسم - ةيدَعِلماو
رثختلا داضم مييقتب انمق .م2005 ربوتكأ ىتحو م2003 ربوتكأ
)Ab( رثختلل ةداضلما ماسجلأاو )Ab IgG( رتكابوكيليه
ًاضيرم 52ـل )يعانلما يمزنلأا ةرياعم( )اسيلأ( ةقيرط ةطساوب
نم نوناعي ًاضيرم 57و ،يناطرس يدعم يدغ مرو نم نوناعي
.)NUD( ةيحرقتلا ريغ ةمختلا
تناك ،ةدعلما ناطرس نم نوناعي ًاضيرم 52 ينب نم :جئاتنلا
13 يف ةبلاس )Ab( يروليب روتكابوكليهل ةداضلما ماسجلأا
ينب نم .)75%( ًاضيرم 39 يف ةبجومو ،)25%( ًاضيرم
تناك .)NUD( ةيحرقتلا ريغ ةمختلا نم نوناعي ًاضيرم 57
ىدل ةبلاس )Ab( يروليب روتكابوكليهل ةداضلما ماسجلأا
)91.2%( نيرخلآا 52ـلا ىدل ةبجومو ،)8.5%( ىضرم 5
صوكنلا دعب ظوحللما فلاتخلاا اذه ىقبي مل .)p=0.043(
ماسجلأا تناك ،)p=0.068( تازيمتلا ليدعتل يدادملإأ
نيذلا )42.3%( ًاضيرم 22 يف ةبجوم )Ab( رثختلل ةداضلما
ينباصلما ةعومجم نم )56.1%( ًاضيرم 32و ناطرسلا نم نوناعي
ةبسنلاب ًاقرف كلانه نكي مل .)NUD( ةيحرقتلا ريغ ةمختلاب
يدادملإأ صوكنلا ليلتح دعبو )p=0.212( لبق نم ةلأسلما هذهل
.)p=0.131(
تاذ ةميق )Ab( رثختلل ةداضلما ماسجلأا ىدل سيل :ةتماخ
يدغلا مرولا يف لقتسلما ؤبنتلا لماع يف امك ةيئاصحإ ةللاد
.يدعلما يناطرسلا
Objective: To evaluate the correlation between anti
CagA antibody (Ab) and presence of gastric cancer.
Methods: In a descriptive cross-sectional study
during October 2003 to October 2005, in the
Gastrointestinal Subspeciality Center in Razi
Hospital, Rasht, Iran, we assessed anti-Helicobacter
Ab immunoglobulin G (IgG) and anti CagA Ab IgG
by the enzyme-linked immunosorbent assay (ELISA)
method in 52 patients with gastric adenocarcinoma
and 57 patients with nonulceric dyspepsia (NUD).
Results: Among 52 patients with gastric cancer, anti-
Helicobacter pylori Ab was negative in 13 (25%) and
positive in 39 persons (75%). Among 57 patients with
NUD, anti-Helicobacter pylori Ab was negative in 5
(8.5%) and positive in 52 patients (91.2%) (p=0.043).
This significant difference did not remain after logistic
regression for adjustment of confounders (p=0.068).
The CagA Ab was positive in 22 (42.3%) patients with
cancer and 32 (56.1%) of the NUD group. There was
no difference in this regard before (p=0.212) and after
(p=0.131) logistic regression analysis.
Conclusion: Anti CagA Ab does not have a significant
value as an independent predictive factor in gastric
adenocarcinoma.
Saudi Med J 2008; Vol. 29 (11): 1606-1610
From the Gastrointestinal and Liver Diseases Research Center
(GLDRC), Guilan University of Medical Sciences, Razi Hospital,
Rasht, Iran.
Received 16th June 2008. Accepted 10th October 2008.
Address correspondence and reprint request to: Dr. Fariborz Mansour-
Ghanaei, Gastrointestinal and Liver Diseases Research Center
(GLDRC), Guilan University of Medical Sciences, Razi Hospital,
Sardar-Jangle Ave, PO Box 41448-95655, Rasht, Iran. Tel. +98 (131)
5535116. Fax. +98 (131) 5534951. E-mail: ghanaei@gums.ac.ir
H
prevalence. This bacterium plays an important role
in the pathogenesis of chronic gastritis, peptic ulcers,
gastric adenocarcinomas, and gastric mucosa-associated
lymphoid tissue lymphomas.1 Chronic infection of
adults with Helicobacter pylori is characterized by the
infiltration of polymorphonuclear and mononuclear cells
and the upregulation of proinflammatory cytokines and
the chemokine interleukin-8 (IL-8).2-4 Particularly, IL-8
secretion causes activation of neutrophils. Although now
we know a lot on the pathogenesis of Helicobacter pylori,
it is not clear why infected individuals develop different
elicobacter pylori is a gram-negative bacterium
infecting human gastric mucosa with worldwide

Page 2

1607
www. smj.org.sa Saudi Med J 2008; Vol. 29 (11)
Anti CagA antibody in patients with gastric cancer ... Mansour-Ghanaei et al
diseases. This can be because of different factors such as
genetic susceptibility of the host, differences in the host
response to the bacteria, differences in host-microbe
interactions, and variety among bacterial strains.5-8 Two
major important virulence markers of Helicobacter pylori,
cytotoxin-associated protein (CagA) and vacuolating
cytotoxin (VacA) encoded by cagA and vacA genes, have
been well described. It has been reported that the CagA
gene was present in approximately 60% of Helicobacter
pylori strains from Western populations but over 90% of
the strains from southeast Asian populations. In contrast
to CagA, the VacA gene was present in nearly all the
Helicobacter pylori strains informed around the world, as
only half of the isolates expressed VacA with vacuolating
cytotoxity.9 The Helicobacter pylori virulence factors
CagA and VacA are implicated in the development
of gastroduodenal diseases. Most strains possessing
CagA also possess the more virulent vacuolating form
of VacA.10 Epidemiological studies have established a
strong association between Cag pathogenicity island
(CagPAI) + Helicobacter pylori and gastric disease based
on either polymerase chain reaction (PCR) data or the
high seroprevalence for CagA,11-24 although according
to some studies, CagA and VacA are not related to the
ability of invasion and adhesion of Helicobacter pylori in
different cell lines in vitro.25 As there are diverse results
on the correlation between anti CagA antibody (Ab) and
presence of gastric adenocarcinoma, we tried to evaluate
this relation in the Gastrointestinal and Liver Diseases
Research Center (GLDRC) of Guilan University of
Medical Sciences in north province of Iran, an area with
a high incidence of gastric cancer.

Methods. This descriptive study was conducted
during October 2003-2005 in the Gastrointestinal
Subspeciality Center in Razi Hospital, Rasht, Iran. The
cases of this study consisted of 52 patients with gastric
adenocarcinoma, and 57 patients with nonulceric
dyspepsia (NUD) who were matched for age and gender
with the cancer group. Including criteria of our study
were suffering from non-cardia gastric adenocarcinoma
confirmed by endoscopy and pathology report (cancer
group). Exclusion criteria were history of chemotherapy,
negative history of any surgery on the stomach (cancer
group). Suffering from NUD without any ulcer or other
pathologies based on endoscopy report (NUD group).
Negative ultrasonography report on existence of any
stone or other gallbladder diseases (in NUD group).
Negative history of blood products transfusion and
not taking bismuth, proton pump inhibitors, or any
antibiotics during last 4 weeks. Considering the including
criteria, the cases were chosen. Ethical approval form was
accepted from research ethics committee of GLDRC of
Guilan, Iran. One blood sample was taken from each of
them to check anti Helicobacter pylori Ab IgG and anti
CagA Ab IgG by enzyme-linked immunosorbent assay
(ELISA) method.
All statistical analyses were carried out using
Statistical Package for Social Science version 11.5. The
test was based on informed consent and the data were
collected and kept confidential. A p value <0.05 was
considered statistical significant.
Results. Totally, 109 patients with gastric cancer
and NUD had our inclusion criteria and were enrolled
in this study. In the gastric cancer group, the patients
age was between 19-85 with the mean of 46.06±14.21
(Kolmofgrov Smirnov p=0.228) and in the NUD group,
the patients’ age was ranged between 25-82 with mean
of 43.64±12.05 (Kolmogrov Smirnov p=0.199). The age
of patients suffering from cancer was significantly higher
than the one with NUD (T-test p=0.009). Age should
be considered as a confounding factor in final analysis of
this study. Among 109 cases of the study, 59 cases were
males (54.1%) and 50 patients were females (45.9%).
Among patients with NUD, 24 patients (42.1%) were
males and 33 patients (57.9%) were females (Table 1).
Since the ratio of female/male between NUD cases and
cancer cases is significantly different (Yate’s corrected
chi-square p=0.014), gender as a confounding factor
was considered as a result of this study.
Totally, 18 samples (16.3%), including 5 patients
(8.8%) with NUD and 13 patients (25%) with gastric
adenocarcinoma, were negative for anti Helicobacter
pylori Ab and 91 samples (83.5%), including 52 patients
(91.2%) with NUD and 39 patients (75%) with gastric
adenocarcinoma, were positive for it. This means that
if we do not consider factors of gender and age, anti
Helicobacter pylori Ab in the NUD group is significantly
higher than the gastric cancer group. Totally, 55 patients
(50.5%), including 25 patients (43.9%) with NUD and
30 cases (57.7%) with gastric cancer, were nonreactive
for anti CagA Ab, and 54 patients (49.5%), including
32 cases (56.1%) with NUD and 22 cases (42.3%) with
gastric cancer, were positive. Therefore, not considering
the factors of gender and age, anti CagA Ab was not
significantly different between our 2 groups. Among 18
patients with negative samples of anti Helicobacter pylori
Ab, 12 patients (66.7%) were nonreactive for anti CagA
Ab, and 6 cases (33.3%) were positive for it. Among
91 cases with positive anti Helicobacter pylori Ab, 43
patients (47.3%) were nonreactive for anti CagA Ab and
48 patients (52.7%) were positive for it (Table 2). So, we
did not find a significant relation between the presence
of anti Helicobacter pylori Ab and anti CagA Ab (Yate’s
corrected chi-square p=0.212). Finally, to eliminate the
probable effect of confounding factors, age and gender,
we used logistic regression module. Age was known as
the only effective variant to distinguish between these

Page 3

1608
Anti CagA antibody in patients with gastric cancer ... Mansour-Ghanaei et al
Saudi Med J 2008; Vol. 29 (11) www.smj.org.sa
2 diseases. According to this module, gender, anti
Helicobacter pylori Ab titer and anti CagA Ab titer were
not known as significant influential factors.
Discussion. In this study, we did not find a
significant difference in anti CagA Ab between 2 studied
groups; NUD and Gastric adenocarcinoma. Limitation
of this study was small sample size of it. This result is not
in concordance with some studies’ results. Shimoyama
et al26 in Japan, assessed 2 groups, 81 cases with gastric
cancer and 81 patients with normal endoscopy. Anti
CagA Ab, by ELISA, was measured. Anti CagA Ab was
positive in 60% of the case group, but just in 44% of
the control group. Indicating that incidence of anti
CagA Ab would increase the risk of gastric cancer.
In Siavoshi et al’s27 findings, CagA was present in
44% of the patients. Nonulceric dyspepsia patients
had a frequency of cagA positivity similar to that of the
overall population (46%). Siavoshi et al’s,27 the CagA was
present frequently more than CagA-negative in patients
with gastric carcinoma (20%) than cagA-negative
in patients with gastric carcinoma (8%). Talebkhan
et al28 determined the frequency of cagA in Iranian
Helicobacter pylori strains and showed that antibodies
against the CagA protein were present in 90.7% of
patients. Ghoshal et al’s29 studies in India indicated that
CagA IgG was more common in gastric neoplasm than
in non-ulcer dyspepsia patients (124/163 [76%] versus
64/101 [63%]) however, comparable to that in healthy
volunteers patients (87/98 [89%], p=NS). Parsonnet
et al30 in California showed that when compared with
the uninfected subjects, patients infected with CagA
positive Helicobacter pylori are at considerably increased
risk of gastric cancer. The CagA negative Helicobacter
pylori are less strongly linked to malignancy and may
only be associated with diffuse type disease. Held et
al31 in Sweden showed that odds ratio was 7.4 (95%
confidence interval [CI] 3.3-16.6) for CagA-positive
relative to CagA-negative subjects. Among antibodies
to Helicobacter pylori ELISA-positive subjects, the
presence of CagA antibodies increased the risk 3.6 times
(95% CI 1.2-11.1). Enzyme-linked immunosorbent
assay-positive CagA-negative infections were associated
with a 4 fold increased risk (OR=4.2, 95% CI 1.0-
17.0) compared to no infection (ELISA-negative and
CagA-negative). According to this study, Although
patients with antibodies to CagA have the greatest risk
of developing gastric cancer, those with CagA-negative
infections run a significantly greater risk than uninfected
persons.
In a study conducted by Gurbuz et al’s32 in Turkey,
32 patients with gastric adenocarcinoma (cases) and 46
patients with NUD (control) were assessed. Helicobacter
pylori was positive in 56% and 71.7% of cases and
controls. Anti CagA Ab was positive in 100% of cases
and 56.5% of control group. It means that incidence of
anti CagA Ab was significantly higher among patients
with gastric cancer and incidence of Helicobacter pylori
was higher among those with NUD. Hussein et al33 in
a comparative study of dyspeptic patients of Iran and
Iraq showed that cagA was found in similar proportions
of strains from both countries (76% in Iran versus 71%
in Iraq) and was significantly associated with peptic
ulcer disease in Iraq (p≤0.01) but not in Iran.
Our results were in concordance with some other
studies. In the study by Yang et al,34 anti CagA Ab was
evaluated among 808 Chinese with chronic superficial
gastritis, chronic atrophic gastritis, peptic ulcer, duodenal
ulcer, or gastric cancer. According to this survey, being
infected by CagA+ strains had more severe injuries in
upper gastrointestinal, but no significant difference
was found in anti CagA Ab among different disease
groups. In another study by Grimley et al35 in England,
anti CagA, anti VacA, and anti Helicobacter pylori Abs
among 148 patients including 4 different groups: 1)
duodenal ulcer, 2) gastric cancer, 3) esophageal cancer,
4) control groups were assessed. This study confirmed
that no significant difference was found between gastric
cancer and duodenal ulcer.
In the study conducted by Lawinczak and
Starzynaska36 in Poland, on the prevalence of anti CagA
Ab presence between 2 groups, 270 cases with gastric
cancer and 205 patients as control group, showed
no difference totally (54.4 versus 42.5). However,
according to this study, being infected by CagA+ strains
would increase the risk of cancer among the young. In
a study conducted by Mitchell et al37 in Australia, 136
Australians and 83 Chinese were included. Ninety-six
Australians suffered from NUD; 29 patients from
duodenal ulcer and 19 patients were symptom free.
Among the Chinese, 48 patients suffered from gastric
Table 1 - Demographic characteristics of patients.
CharacteristicsNonulceric dyspepsiaGastric cancer
Age (years)
Mean±SD
25-82
43.64±12.05
19-85
46.06±14.21
Gender
Male
Female
24 (42.1)
33 (57.9)
59 (54.1)
50 (45.9)
Table 2 - Reactive and non-reactive anti Cag-A Ab among patients with
positive or negative results of anti Hp.
Anti Helicobacter pylori Ab (IgG) NegativePositive
Anti-Cag-A Ab (IgG)
Reactive
Non-reactive
6 (33.3)
12 (66.7)
48 (52.7)
43 (47.3)
Ab - antibody, IgG - immunoglobulin G

Page 4

1609
www. smj.org.sa Saudi Med J 2008; Vol. 29 (11)
Anti CagA antibody in patients with gastric cancer ... Mansour-Ghanaei et al
cancer and 35 patients were symptom free. Results
showed a meaningful relation between anti CagA Ab
and duodenal ulcer in Australians, but no significant
correlation between anti CagA Ab and gastric cancer
among Chinese. They suggested that anti CagA Ab
cannot be considered as a predictive factor in developing
countries.
Some other studies confirmed this suggestion. In a
study by Abasiyanic et al38 in Turkey, 66 patients with
gastrointestinal complaints and 119 ones without any
problems were tested for Helicobacter pylori by ELISA.
Eighty-two percent of patients with symptoms and
64% of symptom free ones were Helicobacter pylori+.
The Helicobacter pylori+ ones were tested for anti CagA
Ab by immunoblot. Anti CagA Ab was positive in
chronic gastritis was 79%, duodenal ulcer was 92%,
gastric cancer was 100%, and symptom free ones was
83%. Meaning that anti CagA Ab was prevalent among
both groups, with or without gastrointestinal problems.
In another study in Japan by Nishiya et al,39 39 patients
with gastric cancer (case) and 39 Helicobacter pylori+
with chronic gastritis (control) were included. The
CagPAI, by PCR, was reported positive in 92.3% of
the cases and 89.7% of the control group; that means,
there was not a significant difference between case and
control groups for the CagA. According to a study on
genetic diversity of CagA in China by Zhou et al,40
CagA, by PCR, was evaluated in 82 Helicobacter pylori+
patients. One hundred percent of patients with peptic
ulcer, 100% of the ones with gastric cancer, 91.4% of
patients with chronic gastritis, and 94.4% of healthy
volunteers had positive CagA reports. Meaning that
presence of CagA cannot be solely considered as an
indicator for Helicobacter pylori related gastrointestinal
disorders among Chinese population.
In conclusion, based on the results of research
developed in different countries especially Asia, we
should not contemplate CagA solely as a risk factor
of gastric cancer, and more research is necessary on
genetic diversity or deletions of CagPAI and possible
effects of it on serum anti CagA Ab presentation in our
country. In the future, performance of this study with
a larger sample size, in the places with high prevalence
of Helicobacter pylori and compare its findings with
neighborhood countries is necessary.
References

1. Ogura K, Maeda S, Nakao M, Watanabe T, Tada M, Kyutoku T,
et al. Virulence factors of Helicobacter pylori responsible for
gastric diseases in Mongolian gerbil. J Exp Med 2000; 192:
1601-1610.
2. Straubinger RK, Greiter A, McDonough SP, Gerold A,
Scanziani E, Soldati S, et al. Quantitative evaluation of
inflammatory and immune responses in the early stages of
chronic Helicobacter pylori infection. Infect Immun 2003; 71:
2693-2703.
3. Maeda S, Akanuma M, Mitsuno Y, Hirata Y, Ogura K, Yoshida H,
et al. Distinct mechanism of Helicobacter pylori-mediated NF-
kappa B activation between gastric cancer cells and monocytic
cells. J Biol Chem 2001; 276: 44856-44864.
4. Zarrilli R, Ricci V, Romano M. Molecular response of gastric
epithelial cells to Helicobacter pylori-induced cell damage. Cell
Microbiol 1999; 1: 93-99.
5. El-Omar EM, Carrington M, Chow WH, McColl KE, Bream JH,
Young HA, et al. The role of interleukin-1 polymorphisms in
the pathogenesis of gastric cancer. Nature 2001; 412: 99.
6. Montecucco C, Rappuoli R. Living dangerously: how
Helicobacter pylori survive in the human stomach. Nat Rev Mol
Cell Biol 2001; 2: 457-466.
7. Peek RM, Blaser MJ. Helicobacter pylori and gastrointestinal
tract adenocarcinomas. Nat Rev Cancer 2002; 2: 28.
8. Rad R, Prinz C, Neu B, Neuhofer M, Zeitner M, Voland P,
et al. Synergistic effect of Helicobacter pylori virulence factors
and interleukin-1 polymorphisms for the development of severe
histological changes in the gastric mucosa. J Infect Dis 2003;
188: 272-281.
9. Chen XJ, Yan J, Shen YF. Dominant CagA/VacA genotypes and
coinfection frequency of H. pylori in peptic ulcer or chronic
gastritis patients in Zhejiang Province and correlations among
different genotypes, coinfection and severity of the diseases.
Chin Med J (Engl) 2005; 118: 460-467.
10. Argent RH, Thomas RJ, Letley DP, Rittig MG, Hardie KR,
Atherton JC. Functional association between the Helicobacter
pylori virulence factors VacA and CagA. J Med Microbiol 2008;
57(Pt 2): 145-150.
11. Bach S, Makristathis A, Pinto A, Quina M, Rotter M,
Hirschl AM. Helicobacter pylori type I strains among Austrian
and Portuguese patients with gastritis, peptic ulcer or gastric
cancer. Eur J Clin Microbiol Infect Dis 1998; 18: 807-810.
12. Evans DJ, Evans DG. Helicobacter pylori CagA: analysis of
sequence diversity in relation to phosphorylation motifs
and implications for the role of CagA as a virulence factor.
Helicobacter 2001; 6: 187-198.
13. Figura N, Vindigni C, Covacci A, Presenti L, Burroni D,
Vernillo R, et al. CagA positive and negative Helicobacter pylori
strains are simultaneously present in the stomach of most
patients with non-ulcer dyspepsia: relevance to histological
damage. Gut 1998; 42: 772-778.
14. Gunn MC, Stephens JC, Stewart JA, Rathbone BJ, West KP.
The significance of cagA and vacA subtypes of Helicobacter pylori
in the pathogenesis of inflammation and peptic ulceration. J
Clin Pathol 1998; 51: 761-764.
15. Haas G, Karaali G, Ebermayer K, Metzger WG, Lamer S,
Zimny-Arndt U, et al. Immunoproteomics of Helicobacter
pylori infection and relation to gastric disease. Proteomics 2002;
2: 313-324.
16. Lai YP, Yang JC, Lin TZ, Wang JT, Lin JT. CagA tyrosine
phosphorylation in gastric epithelial cells caused by Helicobacter
pylori in patients with gastric adenocarcinoma. Helicobacter
2003; 8: 235-243.
17. Matsukura N, Onda M, Kato S, Hasegawa H, Okawa K,
Shirakawa T, et al. Cytotoxin genes of Helicobacter pylori in
chronic gastritis, gastroduodenal ulcer and gastric cancer: an age
and gender matched case-control study. Jpn J Cancer Res 1997;
88: 532-536.
18. Miehlke S, Yu J, Schuppler M, Frings C, Kirsch C,
Negraszus N, et al. Helicobacter pylori VacA, IceA, and CagA
status, and pattern of gastritis in patients with malignant and
benign gastroduodenal disease. Am J Gastroenterol 2001; 96:
1008-1013.

Page 5

1610
Anti CagA antibody in patients with gastric cancer ... Mansour-Ghanaei et al
Saudi Med J 2008; Vol. 29 (11) www.smj.org.sa
19. Occhialini A, Marais A, Urdaci M, Sierra R, Muñoz N,
Covacci A, et al. Composition and gene expression of the cag
pathogenicity island in Helicobacter pylori strains isolated from
gastric carcinoma and gastritis patients in Costa Rica. Infect
Immun 2001; 69: 1902-1908.
20. Owen RJ, Sharp SI, Chisholm SA, Rijpkema S. Identification
of CagA tyrosine phosphorylation DNA motifs in Helicobacter
pylori isolates from peptic ulcer patients by novel PCR-restriction
fragment length polymorphism and real-time fluorescence PCR
assays. J Clin Microbiol 2003; 41: 3112-3118.
21. Pan ZJ, van der Hulst RW, Feller M, Xiao SD, Tytgat GN,
Dankert J, et al. Equally high prevalences of infection with
cagA-positive Helicobacter pylori in Chinese patients with
peptic ulcer disease and those with chronic gastritis-associated
dyspepsia. J Clin Microbiol 1997; 35: 1344-1347.
22. Peters TM, Owen RJ, Slater E, Varea R, Teare EL, Saverymuttu S.
Genetic diversity in the Helicobacter pylori cag pathogenicity
island and effect on expression of anti-CagA serum antibody in
UK patients with dyspepsia. J Clin Pathol 2001; 54: 219-223.
23. Slater E, Owen RJ, Williams M, Pounder RE. Conservation of
the cag pathogenicity island of Helicobacter pylori: associations
with vacuolating cytotoxin allele and IS605 diversity.
Gastroenterology 1999; 117: 1308-1315.
24. Yamaoka Y, Kwon DH, Graham DY. A M(r) 34,000.
proinflammatory outer membrane protein (oipA) of Helicobacter
pylori. Proc Natl Acad Sci USA 2000; 97: 7533-7538.
25. Zhang MJ, Meng FL, Ji XY, He LH, Zhang JZ. Adherence and
invasion of mouse adapted H pylori in different epithelial cell
lines. World J Gastroenterol 2007; 13: 845-850.
26. Shimoyama T, Fukuda S, Tanaka M. CagA seropositivity
associated with development of gastric cancer in Japanese
population. J Clin Pathol 1998; 51: 225-228.
27. Siavoshi F, Malekzadeh R, Daneshmand M, Ashktorab H.
Helicobacter pylori endemic and gastric disease. Dig Dis Sci
2005; 50: 2075-2080.
28. Talebkhan Y, Mohammadi M, Mohagheghi MA, Vaziri HR,
Eshagh Hosseini M, Mohajerani N, et al. CagA gene and
protein status among Iranian Helicobacter pylori strains. Dig Dis
Sci 2008; 53: 925-932.
29. Ghoshal UC, Tiwari S, Dhingra S, Pandey R, Ghoshal U,
Tripathi S, et al. Frequency of Helicobacter pylori and CagA
antibody in patients with gastric neoplasms and controls: the
Indian enigma. Dig Dis Sci 2008; 53: 1215-1222.
30. Parsonnet J, Friedman GD, Orentreich N, Vogelman H. Risk
for gastric cancer in people with CagA positive or CagA negative
Helicobacter pylori infection. Gut 1997; 40: 297-301.
31. Held M, Engstrand L, Hansson LE, Bergström R,
Wadström T, Nyrén O. Is the association between Helicobacter
pylori and gastric cancer confined to CagA-positive strains?
Helicobacter 2004; 9: 271-277.
32. Gurbuz AK, Ozel AM, Yazgan Y, Gunay A, Ozdemir S,
Demirtürk L, et al. Seropositivity against Helicobacter pylori
CagA in Turkish gastric cancer patients. J Clin Gastroenterol
2001; 33: 389-392.
33. Hussein NR, Mohammadi M, Talebkhan Y, Doraghi M,
Letley DP, Muhammad MK, et al. Differences in virulence
markers between Helicobacter pylori strains from Iraq and those
from Iran: potential importance of regional differences in H.
pylori-associated disease. J Clin Microbiol 2008; 46: 1774-
1779.
34. Yang G, Hu F, Jia J. Relation between infection of CagA-
positive Helicobacter pylori and upper gastrointestinal diseases.
Zhonghua Yi Xue Za Zhi 2001; 81: 648-650.
35. Grimley CE, Holder RL, Loft DE, Morris A, Nwokolo CU.
Helicobacter pylori associated antibodies in patients with duodenal
ulcer, gastric ulcer, and gastric and esophageal adenocarcinoma.
Eur J Gastroenterol Hepatol 1999; 11; 503-509.
36. Ławniczak M, Starzyńska T. Helicobacter pylori CagA(+)
infection in gastric cancer patients. Pol Merkur Lekarski 2002;
75: 216-220.
37. Mitchell HM, Hazell SL, LiYY, Hu PJ. Serological response
to specific Helicobacter pylori antigens: antibody against CagA
antigen is not predictive of gastric cancer in a developing
country. Am J Gastroenterl 1996; 91: 1785-1788.
38. Abasiyanik MF, Sander E, Salih BA. Helicobacter pylori anti
CagA antibodies: prevalence in symptomatic and asymptomatic
subjects in Turkey. Can J Gastroenterol 2002; 16: 527-532.
39. Nishiya D, Shimoyama T, Yoshimura T, Tanaka M, Fukuda S,
Munakata A. Genes inside Cag PAI of Helicobacter pylori are not
associated with gastric cancer in Japan. Hepatogastroenterology
2004; 51: 891.
40. Zhou J, Zhang J, Xu C, He L. CagA genotype and variants
in Chinese Helicobacter pylori strains, and relationship to
gastroduodenal disease. J Med Microbiol 2004; 53: 231-235.
Related topics
Al-Shehabi ZA, Zezafon HB, Saleh RS. Clinicopathological study of primary gastric
lymphoma. Saudi Med J 2007; 28: 1506-1510.

Wu YG, Xu XM, Yuan GJ, Li JH, Zhou ZY, Ge W. Inhibition of Akt/protein kinase B
activity sensitizes moderately- to un-differentiated gastric cancer cells to chemotherapy.
Saudi Med J 2007; 28: 1295-1296.
Bhat NA, Chishti AS, Moghazy K, Saeed S, Bisher H. Gastric immature teratoma.
Saudi Med J 2007; 28: 959-960.