Introduction

We are all hoping that the 21st century will be an age of building a society that enjoys healthy longevity. Japan has the longest average life expectancy in the world, ahead of developed countries in Europe and America. However, the critical issue is that a long life is not necessarily a long life in good health. If you ask me what I think are vital for maintaining our bodies into old age, I would definitely say a healthy brain, ability to move (motor functions), and healthy teeth. The maintenance of these functions is probably our biggest challenge.

To enjoy longevity, it is necessary to prevent lifestyle-related diseases such as cancer. From a contemporary view, cancers of the digestive system, such as stomach cancer and colorectal cancer, and cancers of the lung, breast, prostate, and pancreas, etc., can all be considered as lifestyle-related diseases. We have come to understand that these cancers are intimately associated with our lifestyle habits such as smoking and dietary patterns, rather than with family history or heredity.

I’ve mentioned that we must maintain a healthy brain; this involves improving blood circulation in the brain. More specifically, it involves extensive learning and playing, being proactive, adopting challenges, and enriching one’s life without adding stress. We are now in an age where the relationship between the body and mind are being reconsidered. The primary prevention(*) of lifestyle-related diseases is the best way to preserve a healthy body, and this in turn helps to create a healthy mind.

For instance, dementia associated with circulatory disorders such as high blood pressure or diabetes, and Alzheimer’s disease, which is associated with nerve cell abnormalities, have already been labeled as lifestyle-related diseases; and there has been an increasing number of research reports on how improving dietary patterns can prevent these diseases.

Next, let us discuss motor function. If you have a problem with motor function, for example, a persistent, dull ache in the lower back or joints, it will have a direct effect on the range of daily activities you can carry out and on your mood. Furthermore, if you develop osteoporosis, it will have a serious effect on your ability to maintain your back in good condition, due to postural problems; and if you have a hip fracture (femoral head fracture), it will significantly limit the range of daily activities you can carry out.

In other words, these problems will significantly reduce our QOL (quality of life), a term we often hear these days. Improving dietary and lifestyle patterns has been shown to have the most beneficial effect on the maintenance of motor function.
Finally, the third point, the maintenance of good teeth and oral health, is important for the maintenance of a healthy body and mind. In Yasuo Kagawa’s book from the Iwanami shinsho series titled “Seikatsu shukanbyo o fusegu (Preventing Lifestyle-related Diseases)”(1) there is a reference to a set of health guidelines called “Kenko Nippon 21 (Healthy Japan 21).” When examining these guidelines, it is apparent that a large proportion of them are on dental health.

In summary, objectives such as reducing tooth decay in infants, lowering the prevalence of periodontitis in prime-age adults, and keeping as many natural teeth as possible into old age, are described in detail. To achieve these objectives, the authorities mention that the proportion of children who have received topical fluoride treatment before the age of three will be increased.

“Healthy People” movements

Long-term national plans related to health have been put together by governments in countries such as Japan, the United States and Canada. Particularly large in scale are Healthy People 2000 and Healthy People 2010 in the United States. The fundamental purposes of these campaigns are to encourage people to quit smoking, and to improve people’s dietary and lifestyle patterns. Scientists point out that smoking and dietary patterns are risk factors in 70 to 80 percent of cancers that occur in adults. Other major risk factors for cancer include viral infections, radiation, UV, and chemicals. In other words, most cancers in adults occur due to environmental factors–family history and heredity rarely have any influence on the risk of developing cancer. This is why primary prevention of adulthood cancers is possible.

In the United States, health campaigns are being conducted based on these scientific facts. These national campaigns have been carried out in partnership with grassroots organizations. One of their major achievements is the anti-smoking campaign that has taken root. Despite this achievement, the smoking rate still lingers around 25%. There are concerns that this is still very far from the target of reducing the smoking rate to 12% by 2010. This being said, the important thing is that we can see evidence that the anti-smoking campaign and information on the dangerous health effects of smoking have infiltrated our society in various ways. For example, it is prohibited to advertise tobacco products in the mass media such as the TV and radio, auto racing, and public facilities. The dangers of second hand smoke have become widely accepted, and smoking areas of hospitals and public buildings are now strictly isolated.

For example, in McMaster University (located in the outskirts of Toronto) where I used to work, smokers were to always smoke outdoors no matter how cold it was outside. As Canada is a bilingual country, the cigarette boxes sold in Canada have warnings (about the harmful effect of cigarettes) printed on the front- and back- sides of the box in both English and French. Printed using half of the space on both the front and back of the cigarette box are color images of diseases, for example, an endoscopic image of a bronchi in lung cancer, an image of a heart during a heart attack, or an image of a stroke. The purpose is to draw consumers’ attention to the harmful effects of smoking on health.

On the other hand, there is also a lot of support for people who want to quit smoking. For example, nicotine gum and nicotine patches can be purchased without a doctor’s prescription. Another available option is the nicotine nasal spray, which is sprayed onto the mucous membrane of the nose. There are also other measures in place, such as imposing higher cigarette tax rates, and higher retail prices for cigarettes. Recently, a reporter from CNN news announced that the price of a box of cigarettes in New York city has now risen to 7 dollars. In Japan, various aspects of tobacco have a string of serious problems related to the economy, politics and social welfare.

Lung cancer is the leading cause of cancer-related deaths in Japan. Considering this, Japan should follow Europe and America’s example. Although stomach cancer used to be the leading cause of cancer-related deaths in Japan, the death rate from stomach cancer is currently appearing to be on the decline. So far, no studies have found the genes of Japanese people to be particularly vulnerable to stomach cancer.

Stomach cancer

In countries worldwide, death rates from stomach cancer are tending to decline, while death rates from lung cancer are tending to be on the rise. A similar trend has been observed in Japan. There is some interesting data on why stomach cancer is tending to decline. Stomach cancer used to be at the top of the list of cancer-related deaths in the United States as well, but that was more than half a century ago. Since then, stomach cancer death rates of Western countries have declined rapidly in a period of about 30 years, as you can see in the table below. The decline in death rates was particularly prominent in Finland, and in Chile (not included in the table).

During this time, Japan’s stomach cancer death rates continued to rise before it gradually started showing a tendency to decline. From 1993 onwards, stomach cancer became second on the list of cancer death rates among Japanese males; lung cancer moved to the top of the list, and it is continuing to rise today. Japan’s stomach cancer death rate and prevalence are still high relative to the rest of the world. The generally high prevalence of stomach cancer among populations in Japan and Southeast Asia may be suggestive of similarities in the type of food eaten, or the type of ingredients used in food consumed in these countries.

The decline in stomach cancer death rates in the United States happened at almost the same time as the rapid spread of the electric refrigerator in the 1960s. The refrigerator helped keep food fresh. A historical analysis of American diets reveals that the consumption of fresh fruit and vegetables started rising from the 1950s.

In Japan, fresh vegetables became a familiar sight when artificial fertilizers became the common type of fertilizer used for growing vegetables. Researchers have indicated that Vitamin C and vitamin A found in fresh fruit and vegetables are particularly effective for the prevention of stomach cancer. They have also pointed out a relationship between excessive salt intake and the risk of stomach cancer. Salt was used to preserve food in the past, but it is believed that advances in refrigeration and freezing technology changed the methods of food preservation, and as a result, reduced people’s intake of salty foods.

In Europe and America, there was a sharp fall in the intake of nitrates, which was commonly used to process hams, sausages, and bacon. Although the reduction in salt intake has been partly attributed to campaigns held for the prevention of high blood pressure, the reduction in salt intake was largely due to the technological advances in food storage that led to the reduction in the amount of salt used in foods such as processed meats (like those mentioned earlier), pickled vegetables, and salted fish.

Around the time when the death rate for stomach cancer declined in the United States, fluoridation of public water supplies became widely implemented. This could simply be a coincidence. In fact, the fluoridation of public water supplies is still a controversial issue in North America. The diffusion rate of fluoridated drinking water in the 1990s is thought to be 65% in the USA and 35% in Canada. On the US surgeon general’s website is a document that recommends the diffusion of fluoridated drinking water.

However, there are also papers on the damaging effects of fluoridated drinking water on health. Determining whether fluoridation is beneficial or detrimental to health is indeed a difficult task. For example, in a recent study involving animals, the animals in the fluoridated water group showed changes in brain cells that resembled that of human Alzheimer’s disease(3). How are fluoridation and stomach cancer related? Exploring this question leads us to consider tooth decay and periodontitis.

Countries with a low stomach cancer death rate are distributed in East Africa, in areas north of Lake Victoria. Uganda and Sudan have particularly low stomach cancer mortality rates. In these countries, people use well water as drinking water. Topographically, the region is covered in volcanic ash, and is rich in fluorine compounds. According to the report by the World Health Organization (WHO), the ratio of people with dental carries is remarkably low in local residents of this region, particularly in children. The health of teeth is not only has an intimate relationship with drinking water rich in fluorine compounds, but also with a low intake of sugar. Some people in this region have mottled enamel due to dental fluorosis, a condition caused by excessive fluoride.

Nitric acid compounds

Potential substances involved in causing stomach cancer (carcinogens) include nitrosamide compounds, which include nitrosamines and nitrosoureas. These substances are thought to be produced by bacteria in the mouth and stomach using materials derived from food. The bacteria in the mouth use nitric acid and nitrates as materials to produce nitrogen compounds. It is believed that, within the acidic environment of the stomach, these nitrogen compounds react with food-derived amino acid derivatives and produce trace amounts of nitrosamide compounds.

The stomach is a saclike digestive organ that secretes hydrochloric acid, which has bactericidal effect, creating a unique environment that is highly acidic. Vitamin C in the blood is secreted into this environment. Animal experiments have shown that salt reduces the effect of hydrochloric acid, making the stomach environment more prone to the development of stomach cancer. The stomach secretes a proteolytic enzyme called pepsin, which breaks down protein. This enzyme digests food and breaks them down into amino acids and polypeptides that contain nitrogen.

When the stomach acid becomes more neutral, bacteria that produce nitric acid begin to multiply. In the highlands of Colombia, South America, there are high incidences of stomach cancer. It has been reported that when people drink well water, the nitrate in the well water increases the amount of nitric acid and nitrate in gastric juice. If the acidity in the stomach is weak, bacteria in the stomach produce nitric acid. After eating, it takes about one hour at least for the pH of the stomach to fall back down to pH 3 or below. We can therefore say that the defense mechanism of the stomach is weakened after meals.

Nitrate is secreted in the saliva (salivary nitrate), and some of it is converted by the bacteria in the mouth into nitric acid. Juices from vegetables such as spinach and celery contain a lot of nitrates. When these vegetable juices are consumed, the nitrate is absorbed into the body. Following absorption, the amount of nitric acid and nitrate secreted in saliva is known to increase to about ten times the normal amount. In poor dental and oral hygiene conditions, salivary nitrate is often converted to nitric acid by bacteria in the oral cavity. In surveys conducted in Holland, the UK, and the US, an intimate relationship was found between the risk of stomach cancer and tooth loss or poor oral hygiene. However, surveys in Japan yielded contradictory results.

One study investigated the relationship between stomach cancer mortality rate and the dietary intake of food-derived nitrate compounds (which contain nitrogen)(4). The study shows that in various countries there is a positive correlation between stomach cancer mortality rates and nitric acid intake. Japan had the highest intake of nitrate among other countries in 1983, which was when the study was published. This nitric acid is derived from vegetables that contain a lot of nitrates.

Although Europeans and Americans consume a high volume of fresh vegetables, their intake of nitrates is low. It is possible that nitrates were contained in larger volumes in some varieties of vegetables and preserved vegetables that the Japanese commonly consumed, and nitrates may also have been added to food as a food preservative in Japan. There may have been differences in the amount of nitrates in drinking water among the regions as well. From what has been observed, the dietary patterns of Europeans and Americans (which include fresh beef and pork and fresh vegetables) have been reducing the prevalence of stomach cancer, but have been increasing the risks for other types of cancers. There is a limit to the accountability of the hypothesis that nitrosamide compounds cause stomach cancer. This hypothesis alone cannot fully explain why stomach cancer is so common in the Japanese.

Helicobacter pylori

There have been many studies on Caucasians in North America that have found that a type of bacteria called Helicobacter pylori was closely associated to the onset of stomach cancer. There are few Caucasians who have antibodies against Helicobacter pylori, and stomach cancer is known to occur frequently in those who have these antibodies. In contrast, most Japanese adults have antibodies to Helicobacter pylori, but they do not necessarily develop stomach cancer.

Certain conditions make people more prone to stomach cancer, for example, atrophic gastritis(*), and intestinal metaplasia(*). Factors that trigger atrophic gastritis include the intake of foods that are high in salt. People who eat a lot of fresh fruit and vegetables, or take vitamin C, tend to be less likely to develop atrophic gastritis. In Japan, the number of people with atrophic gastritis increases with age. In people with atrophic gastritis, the secretion of gastric acid is reduced, which means that the previously mentioned defense system through hydrochloric acid is reduced, making it easier for Helicobacter pylori to multiply.

In the case of Japanese immigrants to the United States, stomach cancer prevalence rates were still high even if a person was aged 20 at the time of immigration, but the prevalence fell in second-generation immigrants. From this, we can predict that the stomach environment is already determined by what people have been eating before the age of 20. In other words, eating a lot of foods that are high in salt, and eating little fresh fruit and vegetables can possibly create a favorable foundation for the development of atrophic gastritis.

As a result of this foundation, it is believed that the stomach’s exposure to the nitric-acid-based carcinogens is increased, leading it towards cancer. However, there is no medical evidence showing a direct involvement of Helicobacter pylori in the onset of stomach cancer. A stomach environment that allows Helicobacter pylori to multiply makes the stomach prone to stomach ulcers and stomach cancer.

These foods and supplements are currently known to have some effect in preventing stomach cancer: vegetables (listed earlier), fruit, vitamin C, vitamin A, vitamin E, calcium, and green tea. Whether or not green tea has an effect on the prevention of stomach cancer is still a controversial issue. As green tea has a bactericidal effect on bacteria in the oral cavity, there is a hypothesis that taking your time to fully savor the green tea in your mouth before swallowing may help reduce the amount of nitrate inside the stomach. Therefore, when considering the preventive effect of green tea on stomach cancer it is important that we not only consider the amount of green tea that is consumed, but also its temperature, and the ways in which it is consumed.

Risk factors of stomach cancer include foods that are high in salt content, such as salted dry fish and smoked fish, and diets that are high in carbohydrates and low in protein. Processed meats and the nitrate content of water may also be cause for concern. Epidemiological studies show that salty foods consumed while a person is still growing can change the stomach’s internal environment into the “Japanese-type,” i.e., the type that is more prone to stomach cancer. It is important to take salt in moderation because the mucous membrane that protects the stomach (gastric mucosa) is very likely to get damaged by chemical reactions of salt.

Conclusions

In this article, we have examined stomach cancer prevention from the perspectives of food and oral hygiene. The salivary gland, oral cavity, teeth, and stomach are intimately associated with each other through the food that we eat, secretions, and resident bacteria. This organic interplay is affected by environmental factors such as food and smoking.

Early detection and early treatment of stomach cancer due to the spread of screening undoubtedly reduced the stomach cancer mortality rate. However, based on various survey results, researchers have pointed out that the factors discussed so far in this article had an even greater effect on the reduction in mortality rate. I believe that knowing what needs to be improved will give us more confidence that we can prevent stomach cancer.

(*)
Primary prevention:

Primary prevention avoids the development of diseases, such as cancer and other lifestyle-related diseases, through improvements in dietary and lifestyle patterns. In this definition, “diseases” refers to chronic diseases, and does not include acute infections and external wounds. Secondary prevention is aimed at early detection of the abovementioned diseases and early treatment. Tertiary prevention reduces the progression (deterioration) of an already established disease or prevents its relapse, and once the disease is in a stable condition, the aim of tertiary prevention is to restore as much function as possible through rehabilitation and other therapies.

Atrophic gastritis:

The glands in the stomach are of three types: cardiac glands, fundic glands, and pyloric glands (in order from the beginning to end of the stomach). Atrophic gastritis is characterized by atrophy of the stomach glands, particularly the pyloric glands, which occurs due to chronic inflammation. Atrophy may extend to the fundic glands, and the secretion of hydrochloric acid and pepsin is reduced when the condition becomes serious. In this condition, a microscopic finding called intestinal metaplasia can be observed. The cells of the gastric mucosa change to resemble the epithelial cells in the small intestine, and this cellular transformation is called metaplasia.

Intestinal metaplasia:

Intestinal metaplasia is a common condition in atrophic gastritis, in which the gastric mucosa transforms into small-intestine mucosa (as explained above). These cells may cause gastric erosion, or regenerate to compensate for the erosion. Inflammation occurs at sites of gastric erosion, and white blood cells produce oxygen radicals to kill bacteria and other pathogens, but in that process it also damages the DNA in its own epithelial cells. The repetition of this process in chronic inflammation is thought to trigger stomach cancer.

References:
(1) Yasuo Kagawa: “Seikatsu shu kanbyo o fusegu–kenko jumyo o mezashite (Preventing Lifestyle-related Diseases–Achieving healthy longevity)” Iwanami shinsho series, 2000.
(2) Howson CP et al: The decline in gastric cancer: epidemiology of an unplanned triumph. Epidemiol Rev 1986;8:1-27
(3) Varner JA et al: Chronic administration of aluminium-fluoride or sodium-fluoride to 3558 rats in drinking water: alteration in neuronal and cerebrovascular integrity. Brain Res 1998;784:284-298
(4) Milvish SS: The etiology of gastric cancer. J Natl Cancer Inst 1983;71:630647