N. Zendehdel, S. Massarrat, A. Sheykholeslami, et al.
Original Article
Topography of Gastritis and its Severity in 864 First
Degree Relatives of Gastric Cancer Patients
SI
D
Nasrin Zendehdel MD2, Sadegh Massarrat MD•1, Arghavan Sheykholeslami MD1, Naser Rakhshani MD1,3,
Sandra Saeidi MD4, Reza Raee MD5, Hosein Nobakht MD1, Seyed Masoud Tabib MD1, Mehrdad Saliminejhad MD1, Masoud Dooghaie Moghadam MD1, Jafar Nasiri MD1, Kourosh Azimi MD1, Reza Fakhar
MD1, Mehdi Babaei MD1, Reza Didehvar MD1, Nosratollah Mohammadi MD1, Mehdi Tavazoee MD1,
Reza Malekzadeh MD1
ch
ive
of
Abstract
Objectives: Studies on gastric mucosal histological ndings among rst degree relatives (FDR) of gastric cancer (GC)
patients are scarce. The aim is to evaluate the topography and the severity of gastritis among FDR of GC patients.
Design: A total of 989 subjects who were FDR of GC patients, ages 40 – 65 years underwent gastroscopies. When no
gross lesion was found, ve specimens were evaluated according to the Sydney Classication and one for urease testing in
order to determine the type of gastritis and its severity.
Results: Of the 989 subjects, 107 had signicant lesions, including two with GC and one with esophageal cancer. The
864 subjects who had complete morphological data taken from ve gastric areas (two from the antrum and three from the
corpus) comprised 419 males (mean age 48.5±7 years) and 445 females (mean age 47±6.4 years). The H. pylori rate was
76.6%. Normal mucosa was seen in 6.9%, antrum-restricted gastritis in 7.4%, antrum-predominant gastritis in 63.5% and
corpus-predominant gastritis in 20% (both had >80% H. pylori infection) and corpus-restricted gastritis in 2%. More atrophy
was seen in the antrum and corpus of FDR females than males. The severity did not differ between those with one or more
GC patients’ relatives. Forty-nine percent of FDR had atrophy and 9.4% intestinal metaplasia (IM) in the corpus. After the
age of 40, there was progression of intestinal metaplasia from 12.2 to 27.3% in the antrum and from 6.7% to 26.2% in the
corpus during two decades. No high grade dysplasia was found in this mid-age population.
Conclusion: Only one-fth of FDR have H. pylori-induced corpus-predominant gastritis who are at risk for cancer and suitable for eradication. Corpus-restricted gastritis is a rare disease in this area.
Ar
Key words: familial, gastric cancer, gastritis, H. pylori
Authors’ afliations: 1Digestive Diseases Research Center, Tehran University of Medical Sciences, Tehran, 2Department of Internal Medicine, Shohada Hospital Shahid Beheshti University of
Medical Sciences, Tehran, 3Gastroenterology and Liver Disease
Research Center, Iran University of Medical Sciences, Tehran,
4
Gastroenterology Department, Artesh University of Medical Sciences, Tehran, 5 Department of Pathology, Shohada Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
•Corresponding author and reprints: Sadegh Massarrat MD, Digestive Diseases Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. P.O. Box 19615-654,
Tel: +98-218-822-0026, Fax: +98-218-241-5400,
E-mail: massarrat@ams.ac.ir
Accepted for publication: 19 May 2010
Introduction
G
astric cancer (GC) is the leading cause of
cancer deaths among males in some Latin American, Asian countries, and in Iran.1,2 The detection of early GC by routine endoscopic screening of those at risk can improve the survival of
patients.2,3 As H. pylori-induced atrophic gastritis is a precursor of distal GC, its eradication provides the best way for prevention of GC. Among
Archives of Iranian Medicine, Volume 13, Number 6, November 2010 469
www.SID.ir
Gastritis Severity in Relatives of GC Patients
intestinal metaplasia (IM) was categorized according to four grades (none=0, slight=1, moderate=2,
and severe=3). The mean scores of mononuclear
and neutrophil cell inltration were calculated separately for two areas of the antrum and three areas of
the corpus.
H. pylori infection was considered absent when
both the RUT and histology of H. pylori in at least
four out of ve specimens were negative. H. pylori
was conrmed by positive RUT and histological
detection in at least one of the ve specimens. The
type of gastritis was characterized as antral gastritis only or antrum-predominant gastritis when the
mean score of neutrophil and mononuclear cell inltrations in both antral biopsies was higher than
the mean score of the three corpus samples. Corpusrestricted gastritis was considered when the mean
score of neutrophil and mononuclear cell inltration from all three areas of the corpus mucosa was
greater than the mean score from both areas of the
antrum. Corpus gastritis was only considered when
neither neutrophil nor mononuclear cells were seen
in either areas of the antrum. The biomarkers pepsinogen I, II, and gastrin 17 by ELISA (Biohit,
Oslow, and Finland) were measured in the sera of
those with corpus-restricted gastritis. Parietal cell
antibody was measured in these sera by immunouorescence.16
Statistical analysis was done by SPSS (independent t-test and Chi-square t-test). The difference
was considered signicant with a value P<0.05. The
study was approved by Institutional Review Board
of the “Digestive Diseases Research Center of Tehran University of Medical Sciences” in accordance
with the Declaration of Helsinki. Informed consent
was obtained for all participants according to the
guidelines of the Institute.
Materials and Methods
Ar
ch
ive
of
The residential addresses of subjects who underwent surgery for GC in Tehran hospitals during
2002 – 2005 were obtained from various hospital
databases and from the Tehran Cancer Institute.
Contact was made with the patients’ FDR, including
brothers, sisters, children, or parents of GC patients.
All relatives between the ages of 40 to 65 years were
invited to undergo a screening upper GI endoscopy
in the hospital. Before the endoscopy, the patients’
characteristics and number of additional FDR diagnosed with GC were obtained. Participants with had
no macroscopic ndings such as cancer or peptic
ulcer in the duodenal bulb or stomach had biopsy
specimens taken from ve areas of the stomach for
histological examination; two from the antrum (one
just below the incisura angularis from the lesser
and one from the greater curvature), three from the
corpus (one from the lesser curvature in the midarea between the cardia and incisura, one from the
opposite side and one from the fornix, the superior
most part of the stomach). One specimen was additionally taken from the incisura angularis for a rapid
urease test (RUT).
All specimens were xed in formalin, stained by
Hematoxylin and Eosin (H&E) and/or giemsa and
evaluated according to the updated Sydney Classication. In the initial part of the study, two pathologists who were blinded to all clinical and endoscopic data evaluated all biopsies and the rate of
agreement was calculated. The severity of neutrophil or mononuclear cell inltration, atrophy, and
SI
D
those with H. pylori infection, rst degree relatives (FDR) of GC patients are more prone to
GC than the general population.4–8 Morphological changes, such as atrophy and intestinal metaplasia involving the corpus of the stomach are
precancerous conditions for the development of
GC.9,10 There are few studies concerning the
morphological ndings of the stomach in FDR
of GC.11–15 This study has aimed to determine
the topography, severity and extent of the gastritis and other precancerous conditions in FDR
of GC with advancing age, and when one or two
family members have been diagnosed with GC.
Results
During a period of 4 years (2001 – 2004) a total of
989 FDR from 551 families with GC were recruited
to participate in this study. Of these, 357 FDR were
from one GC family and the remaining 632 from
194 families with more than one GC were enrolled.
The number of GC patients who underwent surgery
in Tehran hospitals during the inclusion period was
unknown. However, during 1998 – 2001, 1991 pa-
470 Archives of Iranian Medicine, Volume 13, Number 6, November 2010
www.SID.ir
N. Zendehdel, S. Massarrat, A. Sheykholeslami, et al.
Table 1. Types of gastritis, mean age and H. pylori infection rate among FDR of GC patients (n=808)
Gastritis types
n(%)
Mean age (years)±SD
H. pylori infection, n(%)
Normal mucosa
56 (6.3)
46.4±6.1
3 (5.4)
Isolated antral gastritis
60 (7.2)
46.8±6.7
27 (45)
Antrum predominant gastritis
513 (63.5)
47.4±6.7
457 (89.1)
Corpus predominant gastritis
162 (20)
48.7±6.9
135 (83.3)
Isolated corpus gastritis
17 (2)
51±6.2
4 (23.5)
FDR=rst degree relatives; GC=gastric cancer
SI
D
of cell inltration of three areas of the corpus was
the same as the mean score from two areas of the
antrum. Thus, these cases were classied as having
a corpus-predominant gastritis. The type of gastritis
could not be veried in 56 individuals due to lack
of optimal specimens for evaluation of inammatory cell inltration in one or more areas. The type
of gastritis and H. pylori infection rate are given in
Table 1.
Normal mucosa in all areas was seen in 6.9% of
subjects. Antrum-restricted gastritis was found in
7.4%, while 63.5% had antrum-predominant gastritis and 20% corpus-predominant gastritis. Corpusrestricted gastritis was found in 2%. The mean age
of subjects with all types of gastritis was approximately the same within each type. Subjects with
corpus-predominant gastritis and antrum-predominant gastritis had high H. pylori infection rates of
more than 80%, while the H. pylori infection rate in
corpus-restricted gastritis was low at 23.5%.
The prevalence of precancerous conditions, atrophy and intestinal metaplasia as well as their severity are given in Table 2.
Forty percent of subjects had atrophy of both the
antrum and corpus, 9.4% only in the corpus, 4%
had IM both in the antrum and corpus, and 5.1% in
the corpus only. Therefore, half of the FDR subjects
had precancerous lesions in upper part of stomach.
Less than 6% of them had advanced precancerous
conditions (4.1% severe atrophy in corpus and 1.3%
severe IM in corpus). In table 3 we have shown the
progression of precancerous conditions and their severity with advancing age.
Atrophy in antrum and corpus persists after age 44,
while IM progress in antrum from 12.2% to 19% in
the rst and from 19 to 27.3% in the second decade
and in corpus from 6.7% to 12.3% in the rst and
from 12.3% to 26.2% in the second age decade. In
Ar
ch
ive
of
tients with GC were registered in Tehran.17 Taking
the same number of GC patients observed during
the same time length for the inclusion period in Tehran, the rate of families from which we recruited the
subjects would have been about 27.6% of the total
families with GC.
All invited FDR consented for endoscopy and
study protocol. Ninety-two subjects had signicant
gastric lesions (32 with gastric ulcer, 58 had duodenal ulcer or deformity due to ulcer disease, two
had symptomatic ulcerated gastric cancer, 11 had
severe erosive duodenal erosions, four had combined gastric and duodenal ulcers and one subject
had an esophageal tumor). These patients were
treated accordingly and no protocol biopsies were
obtained. In 17 subjects, histological classication was not possible due to the lack of data from
all areas. Biopsy specimens were evaluated in 864
subjects [419 males with a mean age of 48.5±7.1
and 445 females with a mean age of 47±6.4 years.
(range: 39 to 67 years)]. Ten patients had low grade
dysplasia, localized along the lesser curvature in the
corpus and mostly associated with intestinal metaplasia (IM). High grade dysplasia was not detected
in the areas where biopsy specimens were routinely
obtained. The positivity rate of H. pylori infection
was 76.6%, with a signicant difference in the age
groups that were under and over 50 years (79% vs.
71.1%, P<0.05) but was not signicant difference
between men and women (78.7% vs.74.6%).
The measure of agreement (Kappa value) between
the two pathologists in the evaluation of ve areas
of gastric mucosa in 147 subjects was 0.49 for normal mucosa, 0.55 for antral predominant gastritis,
0.51 for corpus predominant gastritis , 0.37 for any
atrophy in the corpus and 0.47 for any intestinal
metaplasia in the corpus (over all P<0.001).
There were 36 subjects in whom the mean score
Archives of Iranian Medicine, Volume 13, Number 6, November 2010 471
www.SID.ir
Gastritis Severity in Relatives of GC Patients
Table 2. Precancerous conditions in FDR of patients with GC (n=808)
n (%)
495 (61.2)
134 (16.5)
408 (50.4)
169 (20.9)
76 (9.4)
124 (15.3)
65 (8 )
76 (9.4)
38 (4.7)
41 (5.1)
323 (40)
59 (7.3)
32 (4)
14 (1.7)
D
Precancerous conditions
Atrophy in antrum
Moderate to severe
Atrophy in corpus
Moderate to severe
Atrophy in corpus only
IM in antrum
Moderate to severe
IM in corpus
Moderate to severe
IM in corpus only
Atrophy in antrum and corpus
Moderate to severe
IM in antrum and corpus
Moderate to severe
FDR=rst degree relatives; GC=gastric cancer
Table 3. The percentage of precancerous conditions in FDR subjects by age
38–50
44
668
SI
Age (yr) and number of FDR subjects
Age group
Mean age
Number
51–60
54
152
>60
63.6
53
59.7
19.6
46.6
20.8
55.6
11.4
54.8
31
Precancerous conditions in FDR subjects (%)
Atrophy
In antrum
Moderate to severe
In corpus
Moderate to severe
of
ive
IM
In antrum
Moderate to severe
In corpus
Moderate to severe
57.7
14.7
49.1
19.4
12.2
6.6
6.7
3.2
19**
8.4
12.3**
6.1
27.3*
20.5*
26.2#
14.3#*
ch
FDR=rst degree relatives; IM= intestinal metaplasia *Compared to 38 – 50 years. P<0.01; **Compared to 38 – 50 years. P<0.05; #compared
to 51 – 60 years. P<0.05
Table 4. Precancerous conditions in FDR of patients according to numbers of GC in families and gender of the GC patients
Precancerous conditions
FDR of one GC
n=830(%)
FDR of more
than one GC
n=45 (%)
FDR of a male
with GC
n=555 (%)
FDR of a female with GC
n=285 (%)
471 (56.7)
24 (54.5)
303 (54.5)
171 (60)*
Atrophy in corpus
387 (46.6)
21 (46.7)
245 (44.1)
146 (51.2)*
IM in antrum
117 (14.1)
7 (15.5)
76 (13.6)
42 (14.7)
69 (8.3)
7 (15.5)
49 (8.8)
21 (7.3)
154 (18.5)
8 (17.7)
97 (17.4)
60 (21)
Ar
Atrophy in antrum
IM in corpus
Corpus predominant gastritis
* P<0.05; GC=gastric cancer; FDR=rst degree relatives
Table 4 we have shown precancerous lesion of FDR
subjects according to the number of gastric cancer
in family.
The FDR subject with two GC members in their
families had the same percentage and severity of
precancerous conditions as those with only one af-
fected member. FDR of female GC patients had
more atrophy in the antrum and corpus than FDR of
male GC patients (P<0.05).
Parietal cell antibody was positive in 3 out of 17
subjects with corpus-restricted gastritis (titer>1:10).
The mean level of pepsinogen I, pepsinogen II and
472 Archives of Iranian Medicine, Volume 13, Number 6, November 2010
www.SID.ir
N. Zendehdel, S. Massarrat, A. Sheykholeslami, et al.
Ar
ch
ive
of
Once gastritis develops in the antrum, it may progress under certain environmental, socioeconomic
and genetic conditions with advancing age, from the
antrum upward along the lesser curvature to the corpus and may nally lead to atrophic gastritis.18 Biopsy specimens taken during endoscopic from different areas of the gastric mucosa have revealed three
topographic types of gastritis (antrum-predominant,
corpus-predominant and autoimmune gastritis)
aside from normal mucosa. The rst two types of
gastritis are induced by H. pylori infection and the
latter one is associated with multiple autoimmune
reactions and the occurrence of various antibodies
in sera.19
In 1938, the German surgeon Konjetzny, morphologically examined all resected stomachs in GC
patients and described atrophic gastritis with metaplastic changes (Becherzellen Metaplasie as goblet
cells) in all areas of the stomachs, while gastritis of
the peptic ulcer type was almost entirely restricted to
the antral area.20 These metaplastic changes, known
as IM, were conrmed with time by numerous other
authors21–24, particularly when seen to occur in the
upper part of stomach. Gastritis with atrophy and
IM, occurring in each area or in upper part of the
stomach, was therefore considered to be a precancerous condition.25
Mononuclear cell inammation localized more in
the corpus rather than the antrum (corpus-predominant gastritis) with IM found in the antrum and
corpus of stomach of patients with early GC.9 On
follow-up examinations of patients with H. pylori
infection, GC was observed mainly in those with
corpus-predominant gastritis.10 This type of gastritis and its advanced form is frequent in FDR of GC
patients compared with controls.11–15 The severity
of atrophy and IM with advanced stage gastritis in
FDR of GC patients in different studies is illustrated
in Table 5. In these studies, FDR had more frequent
atrophy and IM in the corpus or in the whole stomach when compared with controls. In two studies,
the gastric acid output of subjects was measured and
D
Discussion
found to be reduced in FDR when compared with
controls as a sign of earlier progression of advanced
gastritis in this group.11,13
In our population, due to the high rate of H. pylori
infection, only a small number of subjects had normal mucosa. Antral-restricted gastritis was seen in
only 7.4% of the subjects. The majority of subjects
had antrum-predominant gastritis, mostly H. pylori
infected. Corpus-predominant gastritis was found in
20% of the subjects. Among this group only a small
number had atrophy and IM as precancerous conditions for developing GC. As with our population,
corpus-predominant gastritis was found in 22% of
Scandinavian FDR of GC patients, which was more
than in controls (10%) of the same age (about 47
years).11
The prevalence of corpus-restricted gastritis is 2%
and only a few had parietal cell antibodies. The normal mean of pepsinogen I, ratio of pepsinogen I to
II and gastrin-17 without H. pylori infection is indicative of the presence of an early type of non-infectious autoimmune gastritis, which is quite rare in
our population in comparison with the higher rate in
European studies. One study conducted in Germany
had 7% fundic gastritis among 513 dyspeptic subjects.26 In a study among the Estonian rural population, isolated fundic gastritis was found in 10% of
patients27 and in a Swedish population with a mean
age of 60 years isolated fundic gastritis was seen in
5.6% of cases.28
The severity of morphological changes and percentage of corpus-predominant gastritis in FDR of
GC patients was unrelated to family members with
one or more GC patients. However, the FDR of female GC patients had more atrophy in the antrum
and corpus than FDR of male GC patients, which
was similar to a study from Scandinavia.11 It was
remarkable we had not nd any high grade dysplasia
in the biopsies were obtained.
While no progression of atrophy was documented
after the fourth decade of life with increasing age,
IM increased in the antrum as well as in the corpus.
In the corpus the increase was less than 1% per year
in the rst decade and increased to greater than 1%
per year during the second decade (Table 5).
A shortcoming of this study is the lack of a control
group with no familial history of GC. Inclusion of
healthy subjects for endoscopy purposes is ethically
SI
gastrin 17 were 108±47.3 (g/L), 11.7±10.8 g/L
and 7.6±15 pmol/L, respectively. The mean Values
of ratio of pepsinogen I to pepsinogen II was 13±7.
Archives of Iranian Medicine, Volume 13, Number 6, November 2010 473
www.SID.ir
Gastritis Severity in Relatives of GC Patients
Table 5. The percentage of precancerous conditions (atrophy or intestinal metaplasia) in FDR of GC patients and controls
Authors
Ihamaeki (1979)
FDR (n)
Mean age (yr)
Controls (n)
Mean age (yr)
Atrophy (%)
Cases (controls)
Intestinal metaplasia (%)
Cases (controls)
301 (47)
358 (46)
9 (3)
12 (7)
300 (46)
426 (45.8)
23 (11.4)
15 (2)
El-Omar (2002)
100 (43.7)
60 (44)
25 (3.3) in body
6 (1.6) in body
Sepulveda (2002)
111 (39.1)
77 (49.6)
—
—
Meining (1998)
237 (52.6)
237 (53.6)
—
7.7 (3) in body
Our study
881 (47.7)
—
49 in body
9.4 in body
Chang (2002)
FDR=rst degree relatives; GC=gastric cancer
Sadjadi A, Malekzadeh R, Derakhshan MH, Sepehr
A, Nouraie M, Sotoudeh M, et al. Cancer occurrence in Ardabil: results of a population-based cancer registry from Iran. Int J Cancer. 2003; 107: 113
– 118.
Malekzadeh R, Derakhshan MH, Malekzadeh Z.
Gastric cancer in Iran: epidemiology and risk factors. Arch Iran Med. 2009; 12: 576 – 583.
Sano T, Sasako M, Kinoshita T, Maruyama K. Recurrence of early gastric cancer: follow-up of 1475
patients and review of the Japanese literature. Cancer. 1993; 72: 3174 – 3178.
Lehtola J. Family study of gastric carcinoma with
special references to histological types Scand. J
Gastroenterol Suppl. 1978; 50: 3 – 54.
La Vecchia C, Negri E, Franceschi S, Gentile A.
Family history and the risk of stomach and colorectal cancer. Cancer. 1992; 70: 50 – 55.
Zanghieri G, Di Gregorio C, Sacchetti C, Fante
R, Sassatelli R, Cannizzo G, et al. Familial occurrence of gastric cancer in the 2-year experience of a
population-based registry. Cancer. 1990; 66: 2047
– 2051.
Ogawa H, Kato I, Tominaga S. Family history of
cancer among cancer patients. Jpn J Cancer Res.
1985; 76: 113 – 118.
Lissowska J, Groves FD, Sobin LH, Fraumeni JF
Jr, Nasierowska-Guttmejer A, Radziszewski J, et
al. Family history and risk of stomach cancer in
Warsaw, Poland. Eur J Cancer Prev. 1999; 8: 223
– 227.
Meining A, Bayerdoerffer E, Mueller P, Miehlke S,
Lehn N, et al. Gastric carcinoma risk index in patients infected with H. pylori. Virchows Arch. 1998;
432: 311 – 314.
Uemura N, Okamoto S, Yamamoto S, Matsumura
N, Yamaguchi S, Yamakido M, et al. Helicobacter
pylori infection and the development of gastric
SI
1.
D
References
2.
Ar
ch
ive
of
not justiable and practically not possible in such a
large sample size. In the three studies mentioned in
Table 5, dyspeptic subjects or those at risk for organic diseases without a history of GC in their families were selected as controls.12,14,15 In one study,
the number of subjects was too small to determine
the localization type of gastritis.13 In a study from
Finland that had a large sample size of FDR and
healthy controls, the case group whose mean age
was similar to our population had the same rate of
corpus-predominant gastritis as our study (22% in
cases and 10% in controls).11 In all these studies, the
possibility of decline in prevalence of gastritis and
IM during the last decades of life must be taken into
consideration.29
In conclusion, endoscopic screening in FDR of
GC patients with a mean age of 48 years and a high
H. pylori infection rate in endemic areas for GC is
not justied. Only a fth of this population have
predominant corpus gastritis, mostly H. pylori infected, who are at risk for the development of GC
and available for its eradication. Screening subjects
with serum biomarkers in this high risk group may
spare the number of endoscopies in those with no
morphological changes.30 The autoimmune type of
gastritis is a rare disease in this geographic area.
3.
4.
5.
6.
7.
8.
Acknowledgment
I am sincerely indebted to Dr. M. Stolte (Professor,
Institute of Pathology, Bayreuth, Germany) for his
advice and evaluation of some of the histological
¿ndings and to Dr. F. Djavadi (Liver Unit, University of Southern California, Los Angeles, CA) for
correction of this manuscript.
9.
10.
474 Archives of Iranian Medicine, Volume 13, Number 6, November 2010
www.SID.ir
N. Zendehdel, S. Massarrat, A. Sheykholeslami, et al.
16.
17.
18.
19.
23.
24.
25.
26.
27.
D
22.
SI
15.
21.
Houston 1996. Am J Surg Path. 1996; 20: 1161 –
1181.
Konjetzny EG. Der Magenkrebs, Ferdinand Enke
Verlag, Stuttgart, 1938: 136.
Morson BC. Intestinal metaplasia of gastric mucosa. Br J Cancer. 1955; 9: 365 – 376.
Du Plessis DJ. The distribution of gastritis in carcinoma of stomach. Br J Surg. 1974; 61: 521 – 524.
Skinner JM, Heenan P, Whitehead R. Atrophic gastritis in gastrectomy specimens. Br J Surg. 1975;
62: 23 – 32.
Reynolds KW, Johnson AG, Fox B. Is intestinal
metaplasia of the gastric mucosa a premalignant lesion? Clin Oncol. 1975; 1: 101 – 109.
Correa P. Human gastric carcinogenesis: a multistep and multifactorial process. Cancer Res. 1992;
52: 6735 – 6740.
Massarrat S, Paidlik A, Pittner P, Scmitz-Moorman
P, Wurbs M. The role of certain habits and various
diseases in the occurrence of gastritis. Hepatogastroenterology. 1983; 30: 249 – 253.
Villako K, Tamm A, Savisaar E, Ruttas M. Is intestinal metaplasia of the gastric mucosa a premalignant lesion? Scand J Gastroenterol. 1976; 11:
817 – 822.
Petersson F, Borch K, Franzén LE. Prevalence of
subtypes of intestinal metaplasia in the general
population and in patients with autoimmune chronic atrophic gastritis. Scand J Gastroenterol. 2002;
37: 262 – 266.
De Vries AC, Meijer GA, Looman CW, Casparie
MK, Hansen BE, van Grieken NC, et al. Epidemiological trends of pre-malignant gastric lesions:
a long-term nationwide study in the Netherlands.
Gut. 2007; 56: 1665 – 1670.
Haj-Sheykholeslami A, Rakhshani N, Amirzargar
A, Raee R, Shahidi SM, Nikbin B, et al. Serum
pepsinogen I, pepsinogen II, and gastrin 17 in relatives of gastric cancer patients: comparative study
with type and severity of gastritis. Clin Gastroenterol Hepatol. 2008; 6: 174 – 179.
of
14.
20.
28.
ive
13.
ch
12.
cancer. N Engl J Med. 2001; 345: 784 – 789.
Ihamaeki TT, Varis K, Siurala M. Morphological,
functional and immunological state of the gastric
mucosa in gastric carcinoma families. Scand J Gastroenterol. 1979; 14: 801 – 812.
Meining A, Bayerdoerfer E, Stolte M. Helicobacter
pylori gastritis of gastric cancer phenotype in relatives of gastric carcinoma patients. Eur J Gastroenterol Hepatol. 1999; 11: 717 – 720.
El-Omar EM, Oien K, Murray LS, El-Nujumi A,
Wirz A, Gillen D, et al. Increased prevalence of
precancerous changes of gastric cancer patients:
critical role of H. pylori. Gastroenterology. 2000;
118: 22 – 30.
Chang YW, Han YS, Lee DK, Kim HJ, Lim HS,
Moon JS, et al. Role of Helicobacter pylori infection among offspring or siblings of gastric cancer
patients. Int J Cancer. 2002; 101: 469 – 474.
Sepulveda A, Peterson LE, Shelton J, Gutierrez O,
Graham DY. Histological patterns of gastritis in H.
pylori-infected individuals with a family history of
gastric cancer. Am J Gastroenterol. 2002; 97: 1365
– 1370.
Rose NR, Burek CL. Autoimmune diseases, antibodies to tissue specic endocrine gastrointestinal
and surface receptors. In: Rose NR, ed. Manual of
Clinical Laboratory Immunology. 4th ed. Washington DC: ASM; 1992: 723 – 785.
Mohagheghi MA, Mosavi-Jarrahi A, Malekzadeh
R, Parkin M. Cancer incidence in Tehran metropolis: the rst report from the Tehran populationbased cancer registry, 1998 – 2001. Arch Iran Med.
2009; 12: 15 – 23.
Kimura K. Chronological transition of fundic-pyloric border determined by stepwise biopsy of the
lesser and greater curvatures of the stomach. Gastroenterology. 1972; 63: 584 – 592.
Dixon FM, Genta RM, Yardley JH, Correa P. Classication and Grading of Gastritis. The updated
Sydney System and the participants in the International Workshop on the Histopathology of gastritis,
Ar
11.
29.
30.
Archives of Iranian Medicine, Volume 13, Number 6, November 2010 475
www.SID.ir