Current Evidence-based Cancer Prevention Recommendations for Japanese  

1. Overview

[Current Status of International Evaluation]

Smoking is evaluated as a "convincing" carcinogenic factor for not only lung cancer, but also oral, pharyngeal, laryngeal, esophageal, gastric, pancreatic, liver, renal, urothelial, bladder, and cervical cancers, as well as myelocytic leukemia (IARC 2004). In addition, the risks of oral, pharyngeal, esophageal, gastric, lung, bladder, and cervical cancers are evaluated to be "convincingly" lower for smokers who have stopped smoking than for those who continue to smoke (IARC 2007). For almost all of these cancers, it is indicated that the longer the period of non-smoking, the lower the risk. Smoking is also a cause of not only cancer, but also coronary artery disease (angina, myocardial infarction, etc.) and cardiovascular diseases such as stroke, and respiratory diseases such as pneumonia and chronic obstructive pulmonary disease (COPD).

Passive smoking is considered to be a "convincing" risk factor for lung cancer (IARC 2004). According to a meta-analysis of 55 studies on the relationship of passive smoking and lung cancer, the risk to non-smoking females from passive smoking from their husbands was 1.3 times higher than that in those with non-smoking husbands (Taylor R et al. Int J Epidemiol. 2007). Other diseases related to passive smoking include paranasal sinus cancer, breast cancer (premenopausal), abnormal fetal development (low-birth-weight infant, sudden infant death syndrome, premature birth), respiratory diseases [acute lower respiratory tract infection (child), asthma, chronic respiratory disease (child), eye- and mucous-membrane inflammation, labyrinthitis], heart diseases (heart disease death, acute/chronic heart failure, vascular degeneration) (California Environmental Protection Agency 2005, U.S. Department of Health and Human Services 2006).

[Evidence in Japanese]

The JPHC Study Group has concluded that, in general, increases in the risk of cancer from smoking are "convincing". By location, risk was found to be "convincing" for esophagus, lung, and stomach cancer, "probable" for liver and pancreas cancer, and "possible" for large intestine and breast cancer.

A meta-analysis of 5 cohort studies estimated that the overall risk of cancer in smokers was 1.5 times as high as that in non-smokers (male: 1.6 times, female: 1.3 times). For Japan, pooled data from numerous cohort studies in Japanese subjects indicate that the risk of dying from cancer is approximately 2 times higher in males and 1.6 times higher in females (Katanoda K, et al. JE 2008). This also means that stopping smoking reduces the probability of developing cancer to 2/3 - 1/2 of that in current smokers. Estimating from the above relative risk and the ratio of smokers to non-smokers, approximately 20-27% of cancers in Japanese are caused by smoking (approximately 30-40% for males, 3-5% for females), and could thus have been prevented by not smoking. In a situation where 570,000 people are diagnosed with cancer yearly, 110,000-170,000 developed cancer by smoking. These estimates do not include the influence of passive smoking.

In a cohort study on passive smoking in non-smoking Japanese females, the risk of pulmonary adenocarcinoma, which accounts for over 80% of lung cancer cases in non-smoking females, was approximately 2 times higher in subjects with smoking husbands. On this basis, approximately 30% of lung cancer cases in women are estimated to be caused by passive smoking at home (Kurahashi N, et al. IJC 2008).
>>Top of page

[Current Status of International Evaluation]

Evidence that drinking increases the risk of oral, pharyngeal, laryngeal, esophageal, colorectal (in males), and breast cancers is considered "convincing" (WCRF/AICR 2007) (WHO/FAO 2003). In addition, an increase in risk for liver and colorectal (females) cancers is considered "probable" (WCRF/AICR 2007).

[Evidence in Japanese]

Based on studies in Japanese subjects, the JPHC Study Group has concluded that drinking leads to a "convincing" increase in risk for cancer in general. By body site, the effect on cancers in the liver, large intestine, and esophagus was found to be "convincing."

One cohort study conducted in Japanese subjects indicated that the risk of cancer in general increased by 40% with drinking of 2 'go' or more per day, and 60% with 3 'go' or more (Inoue M et al. BJC 2005). It is estimated that approximately 13% of all cancer in males are caused by the drinking of 2 'go' or more per day. On the other hand, it is also known that a certain amount of drinking has the effect of lowering the risk of myocardial infarction or stroke. Moderate drinking is therefore important. Drinking should be kept within 23 g of alcohol per day [equal to approximately 1 'go' (180 ml) of Japanese sake, 1 large bottle of beer, 2/3 'go' of shochu or awamori, 1 double whiskey or brandy, or 1/3 bottle of wine]. Drinking is not recommended for non-drinkers or people who have alcohol intolerance.

The Healthy Japan 21 campaign sets the "moderate drinking level" at 20 g. For a rough indication of this amount, see:

>>Top of page

There is no single known food product or nutrient that can definitely prevent cancer. There are, however, ingredients in food products, and chemical substances, etc. that are formed during cooking or food preservation that can, if over-consumed, potentially increase the risk of cancer. Eating a balanced diet is therefore a good general principle to disperse risk.

[Current Status of International Evaluation]

Internationally, an increase of gastric cancer through the consumption of salt and high-salt foods is considered "probable". Holding back on the consumption of highly salted foods and the use of alternatives to salt in food processing and preservation is needed.
Vegetables and fruits are suggested to be associated mainly with digestive and lung cancers. It was concluded that vegetables and fruits play a "possible" role in helping prevent oral, pharyngeal, laryngeal, esophageal, gastric, and lung (fruits only) cancers. "Vegetables" in this case does not include grains or tubers. The Joint Expert Committee of the World Health Organization (WHO) and the Food and Agriculture Organization of the United Nations (FAO) recommends consumption of at least 400 g of vegetables and fruits per day to prevent lifestyle-related diseases.

A "possible" increase in the risk of cancer in the esophagus has been noted for drinking mate, a beverage which is customarily drunk extremely hot in South America. Also, in "limited" cases, some study results have suggested an increase in risk for oral, pharyngeal, and laryngeal cancers. It has also been concluded that processed meat and animal meat such as beef, pork, and lamb lead to a "convincing" increase in risk for colorectal cancer. Therefore, the intake of beef, pork, lamb and other meats should be kept within 500 g per week, and processed meat should be avoided as much as possible.
(WCRF/AICR 2007)

[Evidence in Japanese]

The evaluation of salt by the JPHC Study Group revealed that an increase in risk for gastric cancer from salt is "probable." A cohort study conducted in Japanese subjects indicated that, among males, the risk of gastric cancer was higher in the group with larger consumption of salt. A clear correlation was not observed in females, but when data for male and females are combined, the greater the consumption of foods with high levels of salt, such as shiokara (salty fermented squid) or neriuni (sea urchin paste), the higher the risk of gastric cancer (Tsugane S et al. BJC 2004). Cutting down on salt intake would not only be an effective means of preventing gastric cancer, the most common cancer in Japan, but would also lead to the prevention of hypertension and decrease the risk of cardiovascular disease. It is desirable that daily salt  intake be kept as low as possible. According to the Dietary Reference Intakes for Japanese (2005) (formulated by the Ministry of Health, Labour and Welfare), the target level of salt per day is set at under 10 g for males and 8 g for females.

The evaluation of vegetables and fruits by the JPHC Study Group revealed that a decrease in risk for esophageal, gastric, and lung cancers with consumption is "possible." In a cohort study conducted in Japanese subjects, those who ate vegetables or fruits at least once a week were found to have a lower risk of gastric cancer than those who rarely ate them (Kobayashi M et al. IJC 2002), but looking at lifestyle-related diseases as a whole, including stroke or myocardial infarction, etc., the daily consumption of vegetables and fruits is recommended. The Healthy Japan 21 campaign has set a goal for daily vegetable consumption of 350 g.

Eating five small plates of vegetables and one plate of fruit adds up to approximately 400 g, which should be provide a rough indication of a sufficient daily intake.

Many study results have suggested that eating hot food and drinks leads to an increase in esophageal cancer or esophagitis. To avoid damage to the mucosal membrane of the oral cavity and esophagus, hot food and drinks should be allowed to cool before consumption so that is not damaged. Also, the Study Group evaluated that eating processed meat such as ham or sausages has a "possibility" of increasing the risk of colorectal cancer, but on the other hand, for red meat such as beef or pork (chicken is not included), it was judged that there were "insufficient data" at this point. However, considering the international evaluations, excessive consumption should be avoided. The average consumption of meat (including all types of meat) for Japanese is 80 g per day (the National Health and Nutrition Survey in Japan, 2005 by the Ministry of Health, Labour and Welfare).
>>Top of page

[Current Status of International Evaluation]

It is concluded that an increase in physical activity (exercise) leads to a "convincing" decrease in risk of colorectal (colon) cancer, and a "probable" decrease in risk of breast cancer after menopause and of endometrial cancer (IARC 2002, WCRF/AICR 2007).

[Evidence in Japanese]

Based on a study conducted in Japanese subjects, this Study Group evaluated the risk reduction of colorectal (colon) cancer through physical activity as "probable". A cohort study conducted in Japanese subjects indicated that the higher the level of physical activity through work or exercise, the lower the risk of developing cancer in general (Inoue M, et al. AJE 2008). Further, physical activity reduces the risk of death from not only cancer but also from heart disease, and therefore reduces the risk of death in general (Inoue M et al. Ann Epidemiol 2008). Maintaining physical activity is a key for a long and healthy life.
>>Top of page

[Current Status of International Evaluation]

Obesity is evaluated to have a "convincing" effect on increasing the risk of cancer in the large intestine, breast (after menopause), esophagus, body of the uterus, kidney, and pancreas (IARC 2002, WCRF/AICR 2007).

[Evidence in Japanese]

This Study Group has concluded that obesity is a "convincing" factor in increasing the risk of breast cancer after menopause. In addition, the evaluation was "probable" for colorectal cancer. However, in a cohort study conducted in approximately 90,000 middle-aged to elderly (40-64 years of age) Japanese males and females investigating the relationship between BMI [body weight (kg)   body height (m)   body height (m)] and the risk of developing cancer in general, an increase in risk was observed only in thin males with a BMI less than 21 (Inoue M, et al. CCC 2004). Also, in another study conducted in approximately 30,000 middle-aged to elderly (40-64 years of age) Japanese males and females, an increase of risk was observed only in obese females with a BMI of 27.5 or more (Kuriyama S, et al. IJC 2005). In terms of the relationship between BMI and deaths caused by all risk factors, a study conducted in approximately 40,000 middle-aged to elderly (40-59 years of age) Japanese males and females indicated lower risks for males with a BMI of 23-27 and females of 19-25 (Tsugane S, et al. IJO 2002). As can be seen, the association between obesity and cancer in general is not as strong for Japanese as that in Western countries. In fact, it is known that thinness resulting from under-nutrition may lower immunity, and thereby facilitate infection; and weaken blood vessel walls, making cerebral hemorrhage more likely. On the other hand, there are some diseases for which risk is lower as weight is lost, including diabetes mellitus, hypertension, and hyperlipidemia, among others. For people with obesity and any of these diseases, losing weight as a part of their treatment would be effective.
>>Top of page

[Current Status of International Evaluation]

Persistent infection with hepatitis B or C viruses is evaluated to "convincingly" contribute to the development of liver cancer (IARC 1994).

[Evidence in Japanese]

Based on 33 studies of hepatitis B virus (HBV) and liver cancer and 10 studies of hepatitis C virus (HCV) and liver cancer in Japanese subjects, the JPHC Study Group has concluded that HBV and HCV "convincingly" increase the risk of liver cancer. It has been reported, after a follow-up of approximately 150,000 blood donors, that hepatitis-positive people have a 100 times' higher risk of liver cancer than those negative for HBV or HCV markers (Tanaka H, et al. 2004). Given findings that approximately 80% of liver cancer cases occur in HBV- or HCV-infected people, it can be said that liver cancer rarely occurs if a person is not infected with these viruses. Hepatitis B and C viruses are transmitted through blood and body fluid. Possible routes of infection are mother-to-child transmission at birth, blood transfusion or blood product use, and medical practices conducted in the days when infectious risk was still unclear. In addition, medical staff are at risk of infection if accidentally pricked with a needle that has been in contact with the blood of a hepatitis virus-infected person.
It is important for middle-aged to elderly people to be tested for hepatitis virus at a local health center or medical institution, because they may be infected without being aware of it, through past medical practice, etc. This recommendation applies even if they do not recall receiving a blood transfusion or blood product use. (Test dates and costs may differ among testing facilities). If tested positive, further testing will be needed and a liver specialist should be seen to receive treatment to eliminate the virus and reduce inflammation, or to detect liver cancer early. Mother-to-child transmission of HBV can be prevented with obstetric care.

For more information about hepatitis virus infection, visit    "Ministry of Health, Labour and Welfare > Health > Infectious Disease Information > Hepatitis"
>>Top of page

* Viruses/bacteria causing other cancers

[Current Status of International Evaluation]

The percentage of cancers caused by persistent infection with viruses and bacteria, etc. is estimated to be approximately 18% worldwide (IARC 2003). Cancers caused by persistent infections include liver cancer by hepatitis B virus (HBV) and hepatitis C (HCV), gastric cancer by Helicobacter pylori, and cervical cancer by human papilloma virus, which together account for the majority of cases with infections (16%).

[Evidence in Japanese]

The percentage of cancers caused by infection is fairly low in developed countries, accounting for 9%, whereas it is 23% in developing countries. In Japan, however, due to the high number of cases of gastric and liver cancer, cancer caused by infections with HBV/HCV, Helicobacter pylori, and human papilloma virus is estimated to account for 20% of the total, a fairly high ratio among developed countries (IARC 2003).

Human papilloma virus and cervical cancer
It is known that the human papilloma virus, which causes cervical cancer, is [check] sexually transmitted. However, 50% to 60% of sexually active women are HPV-positive, and has been pointed out that the infection is not a so-called sexually transmitted disease, and there is no benefit [check] in using condoms in normal sexual activities to prevent infection with HPV, etc. (Masaki Inoue. Obstetric and gynecological treatment. 92:849-851, 2006). A vaccine for the prevention of HPV infection has been developed and is now under application for approval in Japan. Periodic pap tests are important, regardless of infection or symptoms, as is smoking cessation and other general health-promoting measures.

Helicobacter pylori and gastric cancer
Based on 19 studies on Helicobacter pylori and gastric cancer conducted in Japanese subjects, the JPHC Study Group concluded that it is "convincing" that Helicobacter pylori increases the risk of gastric cancer.
 
In a cohort study in which 40,000 middle-aged to elderly (40 to 69 years old) Japanese were followed-up for 15 years to examine the relationship between Helicobacter pylori and gastric cancer, it was reported that HP-positive people have a greater than 10 times' higher risk of gastric cancer than those who are HP-negative (Sasazuki S, et al. 2006). However, the rate of infection in middle-aged to elderly Japanese people is very high, and it has been reported that while 60% to 90% of people who develop gastric cancer are HP-positive, 40% to 80% of people without gastric cancer are also HP-positive. Whether the risk of future gastric cancer can be reduced by eradication therapy is currently under investigation. At this stage, it is important to receive periodic examinations of the stomach regardless of infection or symptoms, to stop smoking, not to consume too much salt or highly salted foods, and to eat vegetables and fruits frequently.
>>Top of page

2. Other points

Other factors not included in these recommendations for cancer prevention for Japanese are gaining attention.

Coffee and liver and colorectal cancers

The JPHC Study Group has concluded that the preventive effects of coffee on liver and colorectal cancers are "convincing" and "probable," respectively. Results of a number of large-scale studies suggest the possibility that liver and colorectal cancers can be prevented. Internationally, in contrast, no conclusion has been reached due to "insufficient evidence." Investigation in randomized controlled trials is required, as is an understanding of the mechanism of this effect. At this stage, it is not recommended that people who are not used to drinking coffee force themselves to drink it.

Breastfeeding and breast cancer

There are numerous studies showing that breastfeeding for a long period of time reduces the risk of breast cancer in the mother. It was concluded, by the JPHC Study Group also, that the association of breastfeeding with breast cancer prevention is "probable." Preventive effects of breastfeeding on breast cancer are considered to be "convincing" internationally as well. Early menarche, late age at first birth, etc. are known to be definite causes of increased risk for breast cancer, but these factors cannot be changed. Breastfeeding after birth is not only beneficial to the child, but by reducing the risk of breast cancer, also to the mother.

* Other points to remember

Factors suspected of contributing to cancer (animal fat, etc.), although not evaluated as "convincing' or "probable," should be avoided as much as possible, while maintaining a balance between convenience/preference and safety. On the other hand, sufficient consumption of foods that are suggested to have potential preventive effects on cancer (dietary fiber, folic acid, etc.) is recommended. Presently, no single food product or food ingredient has been concluded to definitely prevent cancer. Indeed, one report found that high consumption of β-carotene [20 mg/day (Alpha-Tocopherol Beta-Carotene Cancer Prevention Study Group. N Engl J Med 1994), 30 mg/day (Omenn GS et al. N Engl J Med 1996)], a level that cannot be consumed from the regular diet, increased the risk of lung cancer. Although potential cancer prevention may be indicated for some ingredients, it is advisable that excessive consumption through dietary supplements, etc. be avoided.
>>Top of page