Download Gastric cancer

Epidemilogy and risk factors for
Gastric cancer
DR.Mina tajvidi
radiation oncologist
Gastric cancer
It has remained one of the most
important malignant diseases with
significant geographical, ethnic, and
socioeconomic differences in distribution
the most common forms of cancer
worldwide (excluding non-melanoma skin
cancers) are lung (12.3 percent), breast
(10.4 percent), and colorectum (9.4
percent) while the top three causes of
death from cancer are lung (17.8 percent),
gastric (10.4 percent), and liver (8.8
percent)
GEOGRAPHICAL VARIATION — The incidence of
gastric cancer varies with different geographic
regions. Approximately 60 percent of gastric
cancers occur in developing countries.
Studies of Japanese migrants to the Unites
States have confirmed that early exposure to
environmental rather than genetic factors have a
greater influence on mortality and incidence rates
Intestinal gastric cancer is more common in males and
older age groups. It is more prevalent in high-risk areas and
is likely linked to environmental factors. The diffuse or
infiltrative type, is equally frequent in both sexes, is more
common in younger age groups, and has a worse prognosis
than the intestinal type.
There has been a worldwide decline in the incidence of
the intestinal type in recent few decades that parallels the
overall decline in the incidence of gastric cancer. By
contrast, the decline in the diffuse type has been more
gradual. As a result, the diffuse type now accounts for
approximately 30 percent of gastric carcinoma in some
reported series
PRECURSOR LESIONS FOR
INTESTINAL TYPE CANCERS
Longstanding chronic superficial gastritis caused
by chronic H. pylori infection, pernicious anemia,
or possibly a high salt diet leads eventually to
chronic atrophic gastritis and intestinal
metaplasia. Gastric atrophy is accompanied by a
loss of parietal cell mass and therefore a
reduction in acid production (hypochlorhydria or
achlorhydria), a decrease in luminal ascorbic acid
(vitamin C) levels, and a compensatory increase in
serum gastrin, a potent inducer of gastric
epithelial cell proliferation.
Diet — Large epidemiologic studies demonstrating the
association between diet and gastric cancer were based
mainly upon the amount of food imported and produced
rather than the actual food consumption
Diets low in vegetables, fruits, milk, and vitamin A and
high in fried food, processed meat, and fish and alcohol
have been associated with an increased risk of gastric
carcinoma in several epidemiologic studies
Salt — High salt intake damages stomach mucosa and
increases the susceptibility to carcinogenesis in rodent
Salt — High salt intake damages stomach mucosa and
increases the susceptibility to carcinogenesis in rodent
Smoking — Several studies have examined the
relationship between tobacco smoking and gastric
cancer. A meta-analysis of 40 studies estimated
that the risk was increased by approximately 1.5
to 1.60-fold and was higher in men
Alcohol — A consistent association between
alcohol consumption and the risk of gastric cancer
has not been demonstrated [39,41] . A study from
Europe suggested that daily intake of wine may be
protective
Socioeconomic status — The risk of distal gastric
cancer is increased by approximately twofold in
populations with low socioeconomic status [4245] . By contrast, proximal gastric cancers have
been associated with higher socioeconomic class
Gastric surgery — There is an increased risk of
gastric cancer after gastric surgery, with the risk
being greatest 15 to 20 years after surgery and
then increasing with time
Reproductive hormones — Gastric cancer
incidence rates are consistently lower in women
than men in both high and low-risk regions
worldwide.
Reproductive hormones — Gastric cancer
incidence rates are consistently lower in women
than men in both high and low-risk regions
worldwide.
EBV-associated gastric cancers are characterized
by DNA methylation of the promoter region of
various cancer-associated genes, which silences
the expression of these genes
It is thought that Helicobacter pylori infection
triggers inflammation at the corpus mucosa that
results in atrophy and intestinal metaplasia. H.
pylori infection has been associated with an
approximate 6-fold increase in the risk with
adenocarcinomas distal to the cardia, including
both the intestinal and diffuse types.
There are reports of multiple families
worldwide with hereditary diffuse gastric cancer
due to germline mutations of the E-cadherin gene
CDH1 [81-83] . The disorder has an autosomal
dominant pattern of inheritance. The lifetime
cumulative risk for advanced gastric cancer has
been estimated to be 40 to 67 percent in men,
and 60 to 83 percent in women
The human interleukin 1 beta (IL-1B) gene is the
most important candidate gene in the host that
could affect the clinical outcome of H. pylori
Genetic polymorphisms — Certain
polymorphisms have been associated with gastric
cancer
Polymorphisms of methylenetetrahydrofolate
(MTHF) reductase have been associated with
gastric cancer, mainly in East Asians
Hypertrophic gastropathy and
immunodeficiency syndromes — Hypertrophic
gastropathy (including Menetrier's disease) [50]
and various immunodeficiency syndromes [94,95]
have been linked with gastric cancer
The risk of gastric cancer was increased among
patients with benign gastric ulcers (incidence ratio
1.8), unchanged among patients with prepyloric
ulcers, and decreased among those with benign
duodenal ulcers
Pernicious anemiaincreased risk of intestinaltype gastric cancer. A two- to threefold excess risk
has been reported
Beta-carotene and ascorbic acid are believed to
interfere with the progression to cancer through
their antinitrosation and antioxidant effects, and
thus act as protective factors
SUMMARY
Gastric ulcers, adenomatous polyps, and intestinal
metaplasia have been associated with an increased risk of
gastric cancer. (See above). Gastric cancer developing in
patients considered to be at average risk involves an
interplay of bacterial, host, and environmental facts. Dietary
(nitroso compounds, high salt diet with low vegetables) and
lifestyle factors (smoking and alcohol consumption)
probably account for one-third to one-half of all gastric
cancers. H. pylori infection, especially certain genotypes
(vacAs1-, vacAm1-, and cagA-positive), remains an
important risk factor. The risk is increased further in hosts
who possess specific types of cytokine polymorphisms
tanks