J. Agnantis, MD and Dimitrios H.Roukos, MD
From the Departments of Pathology (NJA) and Surgery (DHR), Ioannina
University School of Medicine, 45110 Ioannina, Greece, firstname.lastname@example.org
cancer is the end result of a multifactorial, multigenetic, multistep
process. Environmental exposures and genetic factors have been
reported to cause gastric cancer but the debate about whether
environment or heritability plays the principal role continuous.
The knowledge of factors that influence gastric carcinogenesis
is determinant for the development of strategies effective for
prevention and treatment.
the past decades various conditions and risk factors have been
identified to predispose to cancer development (Table 1). However,
now most clinical and research attention has been focused on Helicobacter
pylori infection, the preneoplastic lesions chronic atrophic gastritis
and intestinal metaplasia, the free-radicals[1,2] and on familial
gastric cancer predisposition.
- Helicobacter pylori (Hp) infection
An unbelievably large number of reports is increasingly publishing
for the association of Hp and gastric cancer. That is not unexpected
if we think that estimates suggest that about half of the world
population is infected by this bacteria. Previous epidemiological
studies have consistently demonstrated an association between
H. pylori infection and the risk of gastric cancer. Prospective
serological studies have reported that H. pylori carriers are
3 to 6 times more likely to develop gastric cancer than those
without infection[4-6] but most recent data estimate this risk
much lower, about 2-fold. Several questions about the role
of Hp in gastric cancer remain to be elucidated. Until now is
unclear why a very small percentage among Hp carriers will develop
gastric cancer. This fact can not support the aspect that Hp is
the causative and single factor for gastric cancer.
The precise role of H. pylori infection in gastric carcinogenesis
remains unclear and the effect of anti-Hp treatment on the prevention
of gastric cancer are still unknown. [7,8]
- Chronic atrophic gastritis and intestinal metaplasia:
These two lesions are most closely linked to an increased risk
of gastric cancer, specifically the intestinal type. Atrophic
gastritis begins as a multifocal process in the distal stomach.
The state of reduced gastric acid (achlorhydria), as a result
of gastritis, may progress to intestinal metaplasia, dysplasia,
and ultimately carcinoma is thought to represent progress of the
atrophic gastritis. Several investigators suggest that atrophic
gastritis and intestinal metaplasia represent an important intermediate
step in the pathogenesis of endemic, intestinal type gastric cancer.
Pathological studies indicate that both conditions have been reported
in otherwise healthy adults who do not subsequently have gastric
cancer, indicating that neither atrophic gastritis nor achlorhydria
alone is sufficient to cause gastric carcinoma.
- Family history of gastric cancer:
Clustering of gastric cancer within families has been reported
for centuries, most notably in the Bonaparte family. Napoleon,
his father Charles and his grandfather Joseph all died of the
disease, as did several of Napoleon' s siblings. Case control
studies indicate that first-degree relatives (e.g. parent or sibling)
of patients with gastric cancer have two to threefold increase
in the risk of contracting the disease.
Of the other condition and factors included in Table 1, an increased
risk for gastric cancer has been reported for a history of partial
gastrectomy for benign disease, the Barrett' s oesophagus and
a consumption of salted, smoked, or poorly preserved foods. This
latest factor may partially explain the declining incidence of
the disease in the latest decades.
- Pernicious anemia:
Studies of patients with this condition have demonstrated that
is associated with two- to threefold excess risk of stomach cancer.
In such patients an excess risk of gastric carcinoid tumors, may
be the result of prolonged acid suppression, hypergastrinemia
and neuroendocrine hyperplasia. Many observations indicated that
there has been a concern that iatrogenic achlorhydria may result
in an increase in the incidence of intestinal type gastric cancer
and gastric carcinoids, but up to date no study has reported an
increased risk in patients with long term drug induced achlorhydria.[12,
-Partial gastrectomy for benign disease
Distal gastrectomy for benign disorders, particularly peptic ulcer
disease, is associated with an increased risk of gastric cancer,
although an association between gastric ulcer and gastric cancer
has been alleged. Recent meta-analyses indicate that the previous
relative risk remains low until 15 to 20 years after resection
of distal stomach but increases steadily thereafter to the range
approximately 1.5 to 3.0. The delay in the development of gastric
cancer may reflect the time required for a gradual progression
of normal mucosal to intestinal metaplasia to dysplasia and ultimately
- Menetrier's disease
There is numerous case reports link gastric cancer with Menètrier'
s disease, although the rarity of this disease has made it difficult
to determine the strength of this association. [16, 17]
- Gastric adenomatous polyps
Similarly Menètrier's disease, considerable evidence indicates
an increased risk of gastric cancer among patients with adenomatous
polyps of the stomach. The malignant potential of adenomas appears
to be directly related to the size of the polyp and the degree
of the dysplasia.
- Barrett's oesophagus
Studies demonstrate that the marked rise in the incidence of adenocarcinoma
of gastric cardia and distal oesophagus appears to be strongly
correlated with an increase in the incidence of Barrett's oesophagus.
The incidence of cancer in patients with Barrett's oesophagus
has been estimated to be 0.8% per year.
- Blood type A:
Several studies reporting an increased risk of gastric cancer
among persons with blood type A. The risk appears to be more pronounced
for diffuse lesions than for the intestinal type.
- Hereditary nonpolyposis colon cancer syndrome:
Patients with hereditary nonpolyposis colorectal cancer (i.e.
Lynch syndrome II), an autosomal dominant disorder with a high
degree of penetrance, are at increased risk for gastric cancer.
- Low socio-economic status:
Although the link between a higher risk of gastric cancer is inversely
associated with socio-economic status appears to be independent
of occupational exposure, it is difficult to ascertain the relative
contribution of other potential confounding factors, such as overcrowding,
poor sanitation, inadequate preservation of food and poor nutrition.[22,
- Low consumption of fruits and vegetables:
Studies have generally demonstrated that diets rich in fruits
and vegetables are associated with a reduced risk of gastric cancer.
Studies in Japan suggest that the recent decline in deaths from
gastric cancer has been accompanied by a parallel decline in per
capita consumption of salted and dried foods, as well as a parallel
increase in the consumption of fresh fruits and vegetables.[24,25]
- Consumption of salted, smoked, or poorly preserved foods:
Studies have generally demonstrated that excessive dietary salt
has been associated with gastric atrophy in animals and with atrophic
changes in gastric mucosal in humans. Consumptions of highly salted
and pickled foods over a long period may therefore lead to atrophic
gastritis, making gastric mucosal more susceptible to the development
of gastric carcinoma.[26,27]
- Cigarette smoking:
Several cohort and case-control studies have shown a 1,5 to 3,0-fold
increase in the risk of gastric cancer among smokers, although
most studies have failed to demonstrate a clear dose-response
atrophic gastritis and intestinal metaplasia
gastrectomy for benign disease
history of gastric cancer
nonpolyposis colon cancer syndrome
of salted, smoked, or poorly preserved foods
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