Diseases and Life Style: A Large-scale Cohort Study in Japan

265,118 adults aged 40 and above in 6 Prefectures in Japan were followed up for 17 years and age standardized mortality rates from each cause of death were compared by life style variables studied at the time of enrollment. Multifactor-multidisease risk matrix thus constructed revealed that out of 44 causes of death 65.9% and 0% of them showed significantly higher and lower risk respectively in daily cigarette smokers while 2.3% and 34.1% of them showed significantly higher and lower risk respectively in daily consumers of green-yellow vegetables. Possible mechanisms of such associations and effective strategies achieving healthy aging were discussed based on these results.


INTRODUCTION
A clear-cut influence of life styles on the risk of various diseases was observed by a largescale cohort study conducted in 1966-82 in Japan (1).Among many life style components, cigarette smoking was found to be the leading risk factor for most diseases.Daily consumption of green-yellow vegetables was observed, on the other hand, significantly reduce the risk of many diseases including cancer and heart disease.

PURPOSE OF THE STUDY
A large-scale census population-based prospective cohort study was conducted to observed the effect of life-style on mortality from cancer and other major causes of death in Japan.As shown in Fig. 1, 6 prefectures were selected as study areas, taking into consideration of geographical distribution, urban-rural relationship, type of major industries and practice of population-based cancer registry.

METHODS
OF THE STUDY Initial survey was done from October to December 1965 for 265,118 adults aged 40 and above residing in 29 Health Center Districts in 6 prefectures.These people were first surveyed for their life styles, such as smoking, drinking, diet, occupation and reproductive histories by the interview of public health nurses with coverage rate of 94.8% and then followed up for 17 years (1966-82).The study is unique as population followed up was nearly 100% of general population in the study areas.Rate of follow-up was also nearly 100% as long as the study subjects remained in the same health center Districts.Person-years of observation were also large, ranking next to Hammond's study in USA (Table 1).

OF THE STUDY
Major results of 17 years of follow-up are as follows.A total of 55,523 (31,979 males, 23,544 females) deaths including 14,740 (8,974 males, 8,846 females) from cancer occurred during the 17 years period (1966-82) out of 3,849,637 (1,709,273 males, 2,140,364 females) person-years of observation.
The numbers of deaths from all causes and from cancer in each year of follow-up are shown in Table 2.

Risk enhancing factors
Of the life-style risk factors studied, daily cigarette smoking and daily alcohol drinking were observed to significantly raise the risk of dying from 29 (65.9%) and 18 (40.9%)respectively of 44 selected causes of death (Table 3)(1).These was no cause of death which showed significantly lowered risk in daily cigarette smokers.Table 3 Relative risks for 44 causes of deaths by selected life-style variables for daily consumers.

Risk reducing factors
Of the life-style risk factors studied, daily consumption of green-yellow vegetables (2) and of fish were observed to be most important in significantly reducing the risk of dying from 15 (34.1%) and 14 (31.8%) of 44 causes of death, respectively (Table 3).It is noteworthy that no cause of death except one showed significantly elevated risk in daily consumers of greenyellow vegetables.

Multifactor-multidisease risk matrix
Sex-age standardized mortality rates for each cause of death were calculated by each life style component.Cigarette smoking was the leading risk factor for majority of diseases among many life style components studied (Figure 2).
Diseases of which risk is significantly related to habit of cigarette smoking, to habit of alcohol drinking and to both habits are listed in Fig. 3A and diseases of which risk is significantly negatively related to habit of green-yellow vegetables consumption, to habit of fish consumption and to both of them are listed in Fig. 3B.Population attributable risks (or preventable fractions) of daily cigarette smoking for diseases other than cancer are illustrated in Fig. 4A and those for cancer of each site are shown in Fig. 4B. Figure 4 Population attributable risks in males due to daily smoking for selected causes of death (A) and mortality from cancer at selected sites (B).Cohort study, 1966-82, Japan.

Dose-response
relationship.A clear-cut dose-response relationship was observed between cigarette smoking and lung cancer risk both in males and females (Fig. 5).Results are quite similar when compared internationally (Fig. 6)(3).
In January 1981 the author reported in British Medical Journal that non-smoking wives with smoking husbands carry significantly higher risk of lung cancer`).Since then many studies were conducted on the issue.20 out of 25 studies reported by the end of 1990 showed elevated risks of lung cancer in never smoking wives with smoking husbands (Fig. 7).
The risks of lung cancer in non-smoking wives in 14 studies were strikingly higher when husband's heavier smoking was reported (Fig. 8).In our later study, passive smoking was observed to be positively related to cancers of breast, nasal sinus and brain tumor in addition to lung cancer.Positive association with passive smoking was also revealed with ischemic heart disease.

2) Alcohol drinking
Effect of alcohol drinking habits on the risk of various diseases was studied using the cohort study materials.Alcohol related cancers were divided into two groups: interaction with cigarette smoking (+) type such as cancers of mouth, pharynx, esophagus (Fig. 9) and liver and liver cirrhosis, and interaction with smoking (-) type such as cancers of sigmoid colon, rectum and prostate (Fig. 10) (5).In addition, alcohol drinking was observed to significantly elevate risks for cerebrovascular diseases, arterial embolism, accident, suicide and also for all causes of death.
Population attributable risks (AR) were calculated for selected causes of death to observed both independent and combined effects of cigarette smoking and alcohol drinking (Fig. 11).AR for cigarette smoking only is predominant for cancers of all sites, stomach, liver, lung, and urinary bladder and also for all causes of death.On the other hand AR for combined habits of cigarette smoking and alcohol drinking is predominant for cancers of mouth, esophagus, rectum and for cardiovascular disease.AR for alcohol drinking only is predominant for cancer of sigmoid colon and liver cirrhosis(1).

3) Green-yellow vegetables
Daily consumption of green-yellow vegetables (GYV) was observed to significantly lower down risks for cancer of stomach (Fig. 13), colon, lung, cervix, prostate,"' heart diseases (Fig. 12), hypertension, arterial sclerosis, liver cirrhosis and all causes of death.
The risk lowering effects of increased consumption of GYV for lung cancer (Fig. 14A) and for cervical cancer (Fig. 14B) were particularly striking in heavy smokers.
Those with SDA opposite life styles or who smoke daily, drink alcohol daily, consume meat daily but do not consume GYV daily were found to carry far higher risks than for those with SDA like life styles for all causes of death and also for most diseases including cancer.When GYV was consumed daily keeping other habits unchanged (smoking daily, drinking  Figure 9 Relative risks for cancer of the oesophagus in men by daily habits of cigarette smoking and alcohol drinking (*beer, sake; **shouchu, whisky).Cohort study, 1966-82, Japan.
Figure 10 Relative risks for cancer of the prostate by daily habits of cigarette smoking and alcohol drinking (*beer, sake; **shouchu, whisky).Cohort study, 1966-82, Japan.
Figure 11 Proportions of deaths from selected causes among men attributable to daily cigarette smoking only, daily alcohol drinking only and daily both smoking and drinking combined.Cohort study, 1966-82, Japan.daily and consuming meat daily), risks were observed to become much lower for most causes of death than in case GYV was not consumed daily, suggesting beneficial effect of betacarotene and vitamine C as scavengers of oxygen radicals and also of minerals such as calcium and iron plus dietary fibre rich in GYV (Fig. 15).Increased frequency of consumption of GYV was found to slow down the aging process, the mortality rate of daily consumers being equivalent to that of much younger nonconsumers as shown in Fig. 16(1).Cohort study, 1966-82, Japan.

DISCUSSION
A large-scale cohort study for 265,118 adults for 17 years conducted in Japan clearly revealed extent of risk modification of various diseases by selected life style components.Among them strongest influence was observed for cigarette smoking.Not only direct (or active) smoking, indirect (or passive) smoking was observed also to modify the risk of selected diseases such as lung cancer.Such associations are interpreted as due to the long-term inhalation of potent carcinogens and other toxic chemicals in both main stream and side stream of cigarette smoke.Other life style component significantly enhance risks of selected diseases was habit of alcohol drinking with or without smoking habit.
Daily consumption of green-yellow vegetables was observed to lower down risks for cancer, heart disease and also all causes of death probably due to the actions of beta-carotene and vitamine C as scavengers of oxygen radicals plus effects of minerals such as calcium and iron and also of dietary fiber.
These results were considered to be of unique importance in studying the mechanism of causation of each disease and also in formulating strategies for primary prevention of cancer and other major diseases.
We should try to modify our life styles towards the direction of smoking cessation, moderation in drinking alcohol and eating more green-yellow vegetables and possibly also fish.All of these life style modifications were clearly shown in our large scale cohort study in Japan to be desirable for achieving healthy aging.

Figure 1
Figure 1 Geographical location of the prefectures sampled, with numbers of subjects.

Figure 2
Figure 2 Sex-age standardized mortality rate ratio by selected life-style variables.Cohort study, 1966-82, Japan.

Figure 3
Figure 3  Causes of death for which there is a significantly higher (A) or lower (B) sex-and age-standardized mortality rate in daily consumers than in non-daily consumers of cigarettes and alcohol (A) and of green-yellow vegetables and fish (B).Cohort study, 1966-82, Japan.

Figure 5
Figure 5 Relative risk for lung cancer by sex and by number of cigarettes smoked per day.Cohort study 1966-82, Japan.
Figure 6Relative risk for lung cancer by number of cigarettes smoked per day in each cohort study ever conducted.
Figure 7Relative risks of lung cancer among never smoking women Figure 12 Relative risk for stomatch cancer by frequency of green-yellow vegetables consumption.Cohort study, 1966-82, Japan.

Figure 13
Figure 13 Relative risk for heart diseases by frequency of green-yellow vegetables consumption .C ohort study, 1966-82, Japan.

Figure 14
Figure 14 Relative risks for cancer of the lung in men (A) and cancer of the cervix uteri (B) by frequency of consumption of green-yellow vegetables and number of cigarettes smoked per day.Cohort study, 1966-82, Japan.
Figure 15 Relative risk for selected causes of death by different combination of life-style components.Cohort study, 1966-82, Japan.