Download An In-depth Look at Fish Intake and Gastric Cancer among the Asian

Cassie Steck
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An In-depth Look at Fish Intake and Gastric Cancer
among the Asian Community
Cassie Steck
February 14, 2007
PAS 646
Dr. Boissonneault
Abstract
The number or incidence of stomach cancer in the United States has
declined dramatically over the past several decades. However, there are many
countries particularly those of Asia where stomach cancer is a main culprit of
disease. Sodium intake among Asians is considerably higher than that of
Americans based upon daily intake amounts. The main reason for this is
because many Asian cultures depend on fish as a major component to their diet
and culture. Fish that is preserved and processed is often high in salt, which can
promote stomach cancer and can increase the exposure of Heliobacter pylori
bacterium. Substances found in smoking like nicotine also increases the
likelihood of this disease through tumor cell proliferation, angiogenesis,
metastases, increasing salivation, and initiating the inflammatory response. Salt
from the diet can disrupt the stomach lining causing gastric atrophy initiating a
disease process to occur. Nitrites and nitrates from preserved fish combine with
other nitrogen compounds in the stomach converting it to a carcinogen. If a diet
includes high intakes of processed fish and other foods high in salt content the
prevalence for stomach cancer is much higher. Stomach cancer is a major
problem within Asia today. Many of the causes of this disease could be avoided
with the right interventions and changes in diet.
Introduction
Gastric cancer is a deadly occurrence ranking as the second leading
cause of cancer worldwide and accounting for 1 million deaths per year (WHO
2006). Countries with a high incidence include Korea, China, Japan, (i.e. Asia)
while the incidence rates of the United States are relatively low (Smith 2006).
Many researchers do not fully understand the differences in occurrences among
ethnic groups. The development of this disease is determined by a combination
of risk factors, including Helicobacter pylori (H. pylori) infection and poor
socioeconomic conditions, tobacco and diet.1
Asia accounts for an estimated 56.4% of the world’s population alone,
essentially, a continent busting at its seams (Internet World Stats 2001).
Overcrowded areas promote the contraction of H. pylori because it can be easily
passed from person to person by fecal oral routes. Bed sharing as a child and
house crowding is common in this area of the world promoting H. pylori
transmission. This organism infects 60% of the younger population to 90% of the
elderly population in Asian countries (Prinz 2006). If left untreated it can lead to
gastric cancer. H. pylori infects only 30% of Western populations with a mere
0.1-1% developing gastric cancer (Prinz 2006). This may be due to less
populated areas and less strained socioeconomic backgrounds. Intensive
research led to the discovery of this organism in 1983. The incidence of gastric
cancer in the United States has declined considerably with this discovery.
Tobacco use has also been shown to be a risk factor and a cause for
gastric cancer. Smokers are more prone to develop severe ulcers in the
stomach than non-smokers are (Campaign 2003). 10.2% of Chinese, 17.7% of
Japanese, and 21% of Koreans smoke (U.S. Dept. 2006). These numbers are
A risk factor increases a person’s chance of developing the disease but it does not cause the
disease. Some people with one or more risk factors may not develop the disease, while others
develop the disease and have no known risk factors (OHSU 2001).
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comparable to the 20.9% of the United States population that smokes (American
Lung Assoc 2006). One would think that with those factors Americans run as
much a risk for stomach cancer as anyone in the world but when linked with the
dietary differences, and other risk factors, Asians have an increased chance of
developing gastric cancer over Americans.
Foods that are dried, pickled, smoked, and salted such as fish, contain
nitrates which are converted into carcinogenic compounds in the stomach
increasing the likelihood of developing gastric cancer. People living in Asia and
other high-risk areas consume these types of foods more frequently than the
Western population.
Objectives
The purpose of this dialog is to discuss the pathophysiology of gastric
cancer and the significance of the risk factors. Gastric cancer does not have a
high incidence in the United States, but is quite common and deadly in many
other countries in the world. As health care professionals we should not be
concerned with just our own country’s health problems, but we should also be
educated in other worldwide sickness.
Background
The stomach is part of the GI tract that digests and stores food after it has
been passed down from the esophagus. It starts at the gastroesophageal
junction and ends at the duodenum. The stomach consists of three parts: the
cardia, which is the uppermost portion of the stomach, the fundus, and the
pylorus, which connects to the duodenum (eMedicine 2004). Each area has a
different histology. The cardia and pylorus contains mostly mucous secreting
cells (eMedicine 2004). The fundus contains mainly mucous secreting cells,
chief cells, which secrete pepsinogen, and parietal cells, which secrete
hydrochloric acid (eMedicine 2004).
This organ aids in food digestion permitting nutrients to be fully absorbed
by the small intestine, and also to fight off bacteria the person may have
ingested. The autonomic nervous system innervates the cells of the stomach to
stimulate release of their products into the lumen of the gut. The secretions assist
in protection of the stomach lining, breakdown of food, and fighting off harmful
organisms. Depending on the type of food eaten the pH of the stomach varies.
Epithelial cells line the stomach mucosa preventing the penetration of the
secretions, a property that allows the stomach to contain acid and pepsin without
having its own walls digested. Therefore protection of the gastric mucosa is very
important with the introduction of a disease process.
The stomach is a reservoir for food that releases its contents into the
duodenum at a steady rate that promotes nutrient absorption. Vagal nerve
stimulation inhibits smooth muscle contraction of the body of the stomach. This
allows the stomach to hold food without forcing it through the GI system and
decreasing the absorption rate.
In order to understand the spread of the cancer the anatomy and
physiology of the vascular and lymph supply must be known. The celiac trunk
arises off the abdominal aorta and branches into three major arteries: the splenic,
left gastric and common hepatic. The splenic artery gives off the short gastric
and left gastroepiploic arteries that supply the greater curvature. The left gastric
artery supplies the lesser curvature. The common hepatic artery branches into a
right gastric branch that helps to also supply the lesser curvature. The common
hepatic artery also gives rise to a right gastroepiploic artery that helps to supply
the greater curvature.
Lymph drainage follows the arteries from the anterior and posterior aspect
of the stomach to the gastroepiploic lymph nodes. These nodes eventually drain
into the cisterna chyli, which then enters into the thoracic duct. The blood supply
and lymphatic drainage can spread metastases to other organs including the
liver, pancreas, spleen, intestine, and the rest of the body.
Gastric cancer therefore can metastasize through hematogenous spread,
through lymphatic drainage, and it can also grow through the wall of the stomach
invading other organs.
Pathophysiology
H. pylori
There are many risk factors that are considered in the development of
gastric cancer. H. pylori infection is a risk factor that greatly increases the
chances of acquiring gastric cancer. This bacterium can induce physiological
and morphological changes within the gastric mucosa if it is a chronic infection
and/or if it is left untreated. This organism can be transmitted from person to
person by fecal oral route, which is more likely to disperse through poor living
conditions.
This organism is a neutralophile growing best at a pH of six to eight,
which is much higher than the normal stomach pH. It possesses several rare
qualities that allow it to invade the host’s defenses and grow within the stomach
mucosa. H. pylori contain a urease enzyme that “allows it to hydrolyze gastric
urea into ammonia and carbon dioxide” (Smith 2006). This enables the organism
to maintain a neutral pH internally while it’s in the presence of an acidic
environment. H. pylori also seek out an area in the stomach where the pH is
highest so its “acid adaptation machinery” is not overworked (Smith 2006). This
area would be most likely the antrum of the stomach. With the help of antacids
(Tums, Mylanta, and Alka-Seltzer), histamine-2 blockers (Tagament, Pepcid, and
Zantac), and proton pump inhibitors (Prevacid, Nexium, and Prilosec) the pH of
all areas of the stomach can be raised to a more basic environment. All three of
these drugs are available over the counter allowing patients to self medicate
without seeing a physician. A person with dyspepsia that may have H. pylori
could be creating a worsening environment allowing the infection to spread and
possibly leading to gastric cancer. It is imperative that patients be tested for this
organism in the presence of the certain symptoms; if not, H. pylori is then able to
colonize in more distal areas where the pH would presumably be lower. There
are three main phenotypes that result in response to H. pylori infection. Of the
three the corpus mucousa carries the most increased risk of gastric cancer.
Colonization by this organism causes gastritis leading to hypochlorhydria and
gastric atrophy, which increases the risk of gastric cancer if not eradicated by the
right medication. Due to the decrease in the H+ ion concentration nitrogen-fixing
bacteria are able to colonize permitting carcinogenic behavior through the
conversion of nitrates, which is thought to be the main culprit in the progression
of gastric cancer (Smith 2006).
The virulence factor of H. pylori increases the risk of developing gastric
cancer. There are two types of virulence markers in this organsim. Cag A+
genes provoke a more intense gastric inflammation increasing the risk of
adenocarcinoma. Cag A- genes have some deletions, resulting in a less intense
infection. Cag A- genes are rare in Asia, which contributes to the higher
incidence of gastric cancer in this area of the world. While this is a very
important finding in the incidence of gastric cancer in Asia, most health
professionals would agree that the dietary factors are more sufficient cause in the
development of this disease.
Smoking
Cigarette smoke not only affects the lungs but it also induces a negative
impact on the gut. The nicotine in cigarettes is extremely harmful to the lining of
the stomach resulting in increased chances in developing adenocarcinoma of the
stomach. Nicotine has been shown to play a major role in tumor cell
proliferation, angiogenesis, tumor cell metastases, increasing salivation, and
initiating the inflammatory process, which are all characteristics of stomach
cancer growth.
One study from the Molecular Cancer Research suggests that nicotine
induces tumor cell proliferation via the cyclooxygenase two (COX-2) pathway
(Shin 2005). With the use of highly selective COX-2 inhibitors (SC-236), such as
Celecoxib, gastric cancer growth has been limited (Shin 2005). Another study
from the Journal of the National Cancer Institute suggests that nicotine
accelerates stomach cell turnover rate. Abnormal cell proliferation is a hallmark
of tumor formation and growth (In 2001). Substances delivered to the gut from
smoking initiate this process increasing the risk of acquiring a tumor in the gastric
mucosa. Furthermore a COX-2 inhibitor may provide preventative measures
against gastric carcinoma.
Many studies suggest nicotine promotes the release of vascular
endothelial growth factor (VEGF) (Shin 2005). VEGF mediates two VEGF
receptors that are important in angiogenesis. Tumors rely on extra nutrients,
blood supply, and oxygen for growth. With the input of nicotine into the body
VEGF levels are increased promoting gastric cancer growth. Furthermore,
cancerous stomach cells can also increase VEGF, advancing tumor growth even
further.
VEGF, in a healthy non-nicotine environment, suppresses matrix
metalloproteinases (MMP) which promote the adherence of tumor cells;
therefore, metastases are less likely to occur (Shin 2005). The role of VEGF in
an unhealthy nicotine environment has an opposite effect and increases MMP’s
causing the degradation of the adherence of the tumor cells to the extracellular
matrix, promoting gastric cancer spread (Shin 2005).
Salivation increases in the presence of nicotine, which in turn increases
gastric acid secretion, reducing the pH. This correlates with heartburn, an early
symptom of gastric cancer. Previously, if the stomach already had some
mucosal changes the increasing acidity would accelerate this disease process.
Lastly, smoking can also initiate the inflammatory response. Histone
deacetylase is a protein that “down regulates the transcription of inflammatory
genes” (Medscape 2002). Smoking decreases this effect, resulting in an
increase in the inflammatory response. Inflammation in the gastric mucosa
increases the likelihood of H. pylori infection, thus augmenting the chances of
developing gastric cancer.
Fish and Nitrates
An estimated 90 percent of gastric cancer incidence is due to dietary
factors (Strumylaite 2006). This includes and increased intake of highly salted
foods such as salted or smoked fish and salted vegetables, which is a common
daily intake among the Asian population. An intake of carcinogens such as
nitrosocompounds, which are formed during food preservation and during high
temperature cooking, can also increase one’s chances of this deadly disease.
While these are some of the main reasons a patient might have stomach cancer
it is also worth noting that there are others that contribute to this disease.
Individuals consuming diets high in salt and nitrates and low in fresh
vegetables and fruit have an increased risk of developing gastric cancer. Most
Asian communities consume a high volume of salted, preserved, and uncooked
fish, pickled vegetables, and a low volume of fresh fruit and vegetables. Miso
soup and soybeans are fermented soyfood that has a generally high salt content.
Both are consumed five days a week by 20.6% of the males and 17.3% of the
females in the Japanese population (Tsugane 2004). The risk of developing
gastric cancer is higher with the consumption of fermented soyfoods like both of
these two Asian dishes. However, high intake of nonfermented soyfoods such as
soymilk, tofu, and soynuts lowers the risk of this disease. Pickled vegetables
have a salt content of 1 to 10% (Tsugane 2004). Japanese men consume
pickled vegetables 5.1 days per week at a rate of 9.9 grams per day and women
consume pickled vegetables 5.4 days per week at a rate of 8.2 grams per day
during a seven-day period (Tusgane 2004). Salted fish roe, salted fish
preserves, and dried or salted fish is consumed 2.2 days per week at a rate of
9.9 grams per day by the male population and females consumed these foods at
4.5 days per week at a rate of 8.2 grams per day in a seven day period (Tusgane
2004). Local residents of the Fujian Province in China consume about 30mL of
fish sauce as a condiment daily (Cai 2000). Gastric cancer in this area of China
is the most common type of cancer concluding that fish intake is a probable
cause of sickness. A significant increase in the risk of gastric cancer is observed
during a higher consumption of salt including salted and smoked fish. Diets not
including salted or smoked fish but high in salt would also be more susceptible to
gastric cancer than those who consume a low salt diet.
These populations are also exposed to high levels of nitrosocompounds.
The major sources of these potential carcinogens are from diet and cigarette
smoking. Nitrosamines are found mainly in smoked, preserved, dried, pickled,
and salted foods (Jakszyn 2006). “Available data suggests that nitrosamines are
found more frequently and at a higher concentration in Asian foods than in
Western foods” (Jakszyn 2006). This statistic can be due to the way the fish is
prepared and the amount that is consumed. Cooking foods at high temperatures
will also result in the formation of carcinogens that stick to food surfaces.
Exposure of these foods to these carcinogens through cooking has the same
effect in carcinogenesis as preserving fish and vegetables with
nitrosocompounds (Strumylaite, 2006). Foods that have a high content of these
carcinogens and are cooked at higher temperatures are associated with a higher
risk of gastric cancer. These potential carcinogens contained in these foods can
increase cell proliferation and vulnerability to the growth of cancer from the
related salt intake.
The amount of salt consumed by the Asian population through their diet is
the main contributor in the development of gastric cancer. In a study looking at
sodium intake it was found that Japan’s salt intake was much higher and more
significant than the US. The Japanese salt intake among 51 year old men
consumes on average 4082 mg per day; 53 year old women consume on
average 3,970 mg per day (Nagata 2004). The salt intake among the Japanese
continues to increase with age. The United States salt intake among 1,218
people of both sexes ranging between 40 and 59 consume on average 3,375 mg
per day (Wright 2003). This continues to prove that sodium levels play a
significant role among incidence rates through out Asia. Salt initiates the
inflammatory response in the gastric mucosa leading to damage of the protective
stomach lining. This mucosal damage heightens the stomach sensitivity to the
nitrosocompounds and H. pylori infection. This can induce gastritis and cell
proliferation, which is a precursor in the onset of gastric cancer.
While this dialog has centered on the negative effects of fish including salt,
fish does contribute some social and health benefits. Socially, fish plays an
important role to the members of the Asian society and culture. Fish intake also
provides benefits with reproduction and cardiovascular systems.
Docosahexaenoic acid (DHA), most commonly found in fish oil, is an essential
component of the nervous system cell membranes. Pre-natal DHA has shown a
reduction in pre-term delivery, and post-natal DHA is associated with positive
visual and language development. Cardiovascular benefits show a reduction in
lipid levels and platelet aggregation, and it also has an anti-arrythmic effect
(Gochfeld 2005).
Presentation
Gastric cancer is frequently diagnosed in later, more advanced stages
due to nonspecific symptoms, such as heart burn or dyspepsia. At this time it is
usually too late for the patient because the cancer already has a high rate of
metastases. Common complaints are loss of appetite, vague abdominal fullness,
nausea and vomiting, hematemesis, abdominal pain, excessive belching, breath
odor, excessive gas, unintentional weight loss, and premature fullness after
meals (Nanda 2006). Secondary symptoms due to metastatic involvement may
also be present involving lymph nodes of the surrounding areas. A patient’s
history of previous ulcers or peptic ulcer disease, abdominal pain upon palpation
in the physical exam, laboratory studies, and other invasive exams confirm the
diagnosis. An upper GI endoscopy is the gold standard procedure for diagnosing
gastric cancer. Histological studies of biopsies obtained from an upper GI
endoscopy shows low serum levels of prostaglandins one and two, which is 5678% sensitive and 91-100% sensitive of gastric atrophy, a characteristic of
gastric cancer (Rollan 2006). Other diagnostic procedures include: doublecontrast barium swallow, which should be used when an endoscopy is
unavailable, computed tomography (CT) scan in assessing lymph node
involvement, and, endoscopic ultrasonography, which has the ability to image
layers of the stomach mucosa to determine tumor depth (Dale 2006). A fecal
occult blood test (FOBT) can also be used as a preventative measure. A positive
FOBT suggests a disease process occurring that is specific for a GI bleed, which
is associated with gastric cancer.
The prognosis of gastric cancer is based on the penetration of the tumor
(T), the extent of lymph nodes (N) involved, and any metastases (M). There is
also staging within each of these categories to further narrow down the extent of
the cancer. TNM staging is used to determine the mortality and morbidity of the
patient; the earlier the stage the better the outcome for the patient. Stage
grouping is a combination of all TNM stages.
Discussion
This deadly disease was once very prevalent in the United States. Rates
have significantly declined in the US since the innovation of refrigerators and a
decline in the intake of salted foods. According to the American Cancer Society
an estimated 21,260 Americans will still be diagnosed with gastric cancer and
11,210 Americans will die from gastric cancer in 2007 (American Cancer Society
2006). The overall five-year survival rate in the US is 24%, which is dependent
on the stage and location, suggesting that gastric cancer may be due to risk
factors other than dietary components, such as cigarette smoking (American
Cancer Society 2006). The US survival rate is relatively low when compared to
Asians. Mass screenings with endoscopies starting at age 50 has been done to
find gastric cancer at earlier stages due to the higher incidence rates. Asians
have a survival rate of 53% if the cancer is found early (Kim 2003). This
supports the theory that dietary factors play a large role in who develops gastric
cancer.
Adenocarcinomas account for approximately 95% of all gastric cancers
(Dale 2006). These tumors can either be intestinal or diffuse. Intestinal tumors
are a mass of malignant cells that form structures similar to those within the GI
tract. “The intestinal form accounts for the majority of distal cancers and is
associated with H. pylori infection and environmental” (Dale 2006). Diffuse
tumors, which are seen more in younger patients, are malignant cells that have
no unity and lack gastric function. Diffuse cancer has a more severe outlook
than the intestinal cancer. Gastric cancer occurs in all three quadrants of the
stomach. Pylorus and fundus cancer accounts for 80% of all adenocarcinomas,
cardia cancer accounts for 15%, and 10% of gastric cancers include more than
one site infected (eMedicine 2004).
Conclusion
Research continues with the Asian population in an attempt to identify why
gastric cancer is such a potent killer among the eastern people of the world. As
discussed, there are many different causes of gastric cancer but to date none are
more potent or more evident than dietary intake of salt and the effects of smoking
and the substances found in tobacco. The amount of salt found in the diet of the
Asian population along with smoking seems to be causing the confirmed cases of
stomach cancer to be on the rise in Asia. Daily intakes of salt greatly exceed that
of the American diet concluding salt intake is a major contributor of causing
gastric cancer. Prevention in the future should include education about the
harmful effects of too much salt intake along with a change in dietary habits
without changing the entire culture of the eastern people. Today there is not an
absolute positive to link stomach cancer to the habits inherent to the Asian world,
but most scientists and doctors would agree that a reduction in the consumption
of salt and the use of tobacco would reduce the risk of gastric cancer in the Asian
population and worldwide.
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