Comparative Study of Lifestyles of Residents in High and Low Risk Areas for Gastric Cancer in Jiangsu Province , China ; with Special Reference to Allium Vegetables

There is a low risk area for gastric cancer in Jiangsu Province, China, where people frequently consume raw allium vegetables. As a first step epidemiological study to clarify the factors involved in the low incidence of gastric cancer, we conducted a comparative study of the ecological factors in a high risk area (HRA), Yangzhong, and a low risk area (LRA), Pizhou, using a questionnaire. Subjects were selected from the general population according to age and sex, and comprised 414 residents of the HRA and 425 residents of the LRA. Ecological factors were compared for the two areas by Cochran-Mantel-Haenszel method, age-adjusted. Smoking and drinking habits were found to be more common in the LRA. On the other hand, allium vegetables were consumed in the LRA much more frequently, with high consumption of raw vegetables, fruit, tomatoes, kidney beans and soybean products. People who consumed garlic en masse 3 times or more per week were 82% of men and 75% of women in the LRA, and 1 % of men and women in the HRA. The results of the survey suggest that frequent consumption of allium vegetables, in addition to other anticancer foods, may be a factor in low mortality for gastric cancer. J Epidemiol, 1999 ; 9 : 297-305

As a first step epidemiological study to clarify the factors involved in the low incidence of gastric cancer, we conducted a comparative study of the ecological factors in a high risk area (HRA), Yangzhong, and a low risk area (LRA), Pizhou, using a questionnaire.Subjects were selected from the general population according to age and sex, and comprised 414 residents of the HRA and 425 residents of the LRA.Ecological factors were compared for the two areas by Cochran-Mantel-Haenszel method, age-adjusted.Smoking and drinking habits were found to be more common in the LRA.On the other hand, allium vegetables were consumed in the LRA much more frequently, with high consumption of raw vegetables, fruit, tomatoes, kidney beans and soybean products.People who consumed garlic en masse 3 times or more per week were 82% of men and 75% of women in the LRA, and 1 % of men and women in the HRA.The results of the survey suggest that frequent consumption of allium vegetables, in addition to other anticancer foods, may be a factor in low mortality for gastric cancer.
J Epidemiol, 1999 ; 9 : 297-305 ecological study, gastric cancer, allium vegetables, China China is one of the highest risk areas for gastric cancer in the world1).Gastric cancer is the leading cause of cancer death in China, and it has slightly increased in the last two decades 2).The increased risks of gastric cancer for income, occupation, smoking, mental injury, overeating, high salt consumption, low animal protein consumption, and frequent intake of sweet potatoes, sour pancakes and a fermented staple have been addressed in several studies in China 3-7).A positive relationship between gastric cancer and Helicobacter pylori infection has also been reported in China8,9).Moreover, a decreased risk of gastric cancer for high consumption of allium vegetables has been reported in a study in Shandong Province, China 10).
Many experimental studies in vivo and in vitro have shown that extracts and compounds derived from allium vegetables, especially from garlic, have a variety of protective effects against the development of cancer [11][12][13][14].There are, however, few epidemiological studies showing a decreased risk of cancer for allium vegetable consumption.One reason is that largescale consumption of allium vegetables is uncommon.Seven epidemiological studies have shown a consistent association between garlic consumption and a decreased risk of gastrointestinal cancer12).The negative association of allium vegetable consumption and the risk of nasopharyngeal and endometrial cancers has already been found in China 15.16).However, two studies from China 17)and the Netherlands 18) have failed to show a significant association between allium vegetable consumption and a decreased risk of lung cancer after adjustment for other variables.
A comparative ecological study between high and low risk areas may yield valuable information, especially when the level of exposure to specific environmental factors is common to people living in the same area but very different in two con-trasting high and low risk areas.We have found such high and low risk areas for gastric cancer in Jiangsu Province, China.
The people living in the low risk area have a diet unusually rich in raw allium vegetables.
We have hypothesized that frequent consumption of allium vegetables decreases the incidence of gastric cancer.As a first step epidemiological study to clarify the factors involved in the low incidence of gastric cancer and to be followed by further analytical studies, we have conducted an ecological study comparing the exposure level to environmental factors for gastric cancer in high and low risk areas in Jiangsu Province, China.

MATERIALS AND METHODS
Yangzhong City is located on an island in the Yangtze River in the south of Jiangsu Province, China (Figure 1).The population was given as about 273,700 in a 1992 census.Although the major industry of Yangzhong was formerly agriculture, the area's economic status has improved remarkably with the recent development of manufacturing.Pizhou City, with a population of around 1.46 million, is located inland in the north of Jiangsu Province.The major industry of Pizhou is still agriculture, notably garlic production.
A nationwide survey of cancer incidence and mortality was conducted in selected cities in all the provinces of China, between 1990 and 1992.Initial data from death certificates was actively confirmed at all hospitals.In Jiangsu Province, eight cities, including Pizhou, were selected as representative of the average rate of cancer mortality, according to data in a nationwide survey of 1973-1975.The combined population (6.99 million) was 11.5% of the total population of Jiangsu Province.
The age-adjusted mortality rates (AMRs) for selected sites of cancer in Pizhou, and in urban and rural areas in all eight cities in Jiangsu Province were calculated using the data in the nationwide survey.Data on Yangzhong was obtained from local cancer registries, including active confirmation at hospitals.Segi-Doll's World Population 19) was used as a standard population for age adjustment.
Questionnaire studies were conducted independently in Yangzhong City and Pizhou City in 1995-1996.Subjects were conveniently drown from the general population in 5 towns out of 12 in Yangzhong and 5 towns out of 36 in Pizhou according to age and sex by trained local staff at health stations in each town, who interviewed the inhabitants.The age of subjects in Yangzhong and Pizhou was 30-76 (median: 46) and 30-79 years (median: 45) in men, and 30-74 (median: 47) and 30-76 years (medium: 44.5) in women, respectively.The response rate for interview was more than 95% in both areas.The subjects in Yangzhong and Pizhou comprised 201 men and 213 women, and 215 men and 210 women, respectively.
The questionnaire included 152 items; demographics, water supply, dietary habits, food consumption frequency (at the time of the interview and 10 years previously), smoking, alcohol drinking, and tea consumption.The items on smoking habit included smoking status (current, ex-or never), age started smoking, age quit smoking, and number of cigarettes per day.Ex-smokers were defined as those who had quit smoking more than one year prior to interview.Drinking habits included frequency, kinds of alcohol (beers, hard liquors, medium liquors, and fruit liquors) and total amount of alcohol consumption.Alcohol consumption for each type of beverage was determined by the average number of drinks consumed at one time, which was then converted into alcohol weight (grams).One regular bottle (620 ml) of beer was equated to 22 grams of ethanol, and 100 ml of hard, medium and fruit liquors were equated to 55, 38 and 40 grams of ethanol, respectively.Tea drinking habits included regularity of drinking, years of drinking, kind of tea (green, jasmine and black tea), and dose of tea consumption.Tea consumption was rated according to the average number of grams consumed per month.The consumption frequencies of selected foods were rated in six categories and compared for the two areas after grouping in two categories.Allium vegetables included garlic (Allium sativum), Welsh onion (Allium fistulosum), onion (Allium cepa) and Chinese chives (Allium tuberosum).Welsh onion was accordingly not included in green yellow vegetables.Subjects were asked to record the frequency of garlic and Welsh onion consumption only when these were consumed en masse, such as a clove of garlic (4-6 gram), as use of these items as condiments was deemed to be insignificant.
The percentage proportion of each variable for the total number of subjects was calculated by area and sex.Then, lifestyles and dietary habits were compared in the two areas by sex, using the Cochran-Mantel-Haenszel method, age-adjusted.The P-value was calculated after age-adjustment in 5 strata for every 10 years between 30-79 years of age.Factor analysis was done for a number of present variables, including area, sex, income, education, occupation, water supply, smoking, alcohol drinking, tea consumption, dietary habits, cereal consumption and 22 food items.Three factors were chosen according to the proportions of the correlation matrix following Varimax rotation.PROC FREQ and PROC FACTOR from the SAS system were used for these calculations 20,21)

Age adjusted mortality rates for selected cancers
The AMRs for esophageal and gastric cancers in Yangzhong were much higher than those in Pizhou, or in urban or rural areas of Jiangsu Province for both men and women (Table 1).
The AMR for gastric cancer in Pizhou was also half of that in rural areas of Jiangsu Province.Colorectal cancer was less common in Pizhou, and liver cancer was more common in Yangzhong and Pizhou than in urban areas.On the other hand, the AMR for lung cancer was higher in Pizhou and urban areas than in Yangzhong.In Pizhou, the AMR for gastric cancer was lower than the AMRs for cancers of the esophagus, liver or lung, in both men and women.The AMRs from causes other than cancer in Yangzhong and Pizhou were similar (472.6 per 100,000 vs. 494.7 per 100,000).

Demography
Age and sex distribution of subjects was not different in the two areas, although the proportion of subjects aged 60 years or over was relatively low overall (Table 2).Average age of subjects in Yangzhong and Pizhou was 47.7 and 47.4 years in men, and 47.1 and 46.6 years in women, respectively.Present and previous income of subjects in Yangzhong were higher than those in Pizhou.More subjects in Pizhou had had no education, but the proportion of farmers was similar in the two areas.Higher quality water supplies, e.g., tap water or deep well, were more common in Yangzhong than in Pizhou both at the time of the study and 10 years previously.Such high quality water supplies were uncommon in both areas 20 years previously.

Smoking and drinking
The prevalence rate for current and ex-smokers was higher in Pizhou than in Yangzhong (Table 3).The percentage proportion of everyday alcohol drinkers was not different in the two areas, but more subjects in Pizhou had begun to drink before 20 years of age, had drunk for 20 years or more , or consumed ethanol in quantities of 75 grams and more at one time, than in Yangzhong.

Dietary habits and cereals
In Yangzhong, mealtimes were less regular, and food was taken at high temperatures more frequently by men in Yangzhong than in Pizhou (Table 4).More men and women in Pizhou preferred salty foods than those in Yangzhong.Selected foods and Allium vegetables Meat and fish were consumed more frequently in Pizhou, but the proportion of people who consumed them 3 times or more per week stood at 10% or less in either areas (Table 5).

Consumption
of meat, fish, poultry, eggs and milk had increased over the previous 10 years in both areas.
Processed and cooked foods such as fried food, fermented food and soybean products were consumed much more frequently in Pizhou.
Raw vegetables, kidney beans, tomatoes, sweet potatoes and fruit were consumed more frequently in Pizhou, but, as a whole, vegetables were consumed more frequently in Yangzhong.The consumption frequency of pickled vegetables had been higher in Pizhou 10 years previously.In Pizhou, trend towards raw vegetable and fruit consumption was found to be growing, while consumption of pickled vegetables and sweet potatoes had decreased remarkably over the previous 10 years.
Consumption of allium vegetables was notably higher in Pizhou.The proportion of people who consumed garlic en masse 3 times or more per week at the time of the survey was 82.3% of men and 74.7% of women in Pizhou, and 0.5% of men and women in Yangzhong.Although onions and Chinese chives were not consumed as much as garlic and Welsh onions overall, consumption of these was also more frequent in Pizhou than in Yangzhong.The consumption frequency of these allium vegetables had not changed over the previous 10 years in either area.
Frequent consumption of foods, including garlic and Welsh onions, was found not to be dependent on age in either area, when young (30-54 years) and old (55-79 years) subjects were compared (data not shown in Tables).

Factor analysis
Factor analysis yielded a first cluster of area-related variables positively associated with the characteristics of Pizhou residents, namely, frequent consumption of Welsh onions, wheat crackers, garlic, raw vegetables, kidney beans, soybean products, fermented food, tomatoes, eggs and fruit, less frequent consumption of rice, lower income, and lower quality water supplies (data not shown in Tables).A second factor consisted of gender-related variables such as smoking and alcohol drinking.The variables associated with tea consumption clustered as a third factor.The cumulative rate for the attributable proportion of these three factors was 32.9%.

DISCUSSION
The subjects in the present study were drawn from the general population in both areas.The distribution of occupations in Yangzhong and Pizhou respondents was concordant with that obtainable from official records for each area .Local health officials conducted interviews, and recorded responses , with a response rate of more than 95%.Selection bias in the present study, therefore, may be assumed to be negligible .However, the proportion of the total population providing subjects was  only about 0.15% in Yangzhong and 0.03% in Pizhou.It cannot be claimed with confidence, therefore, that the present subjects comprise a representative sample of the general population of each area, because random errors cannot be completely excluded from the analysis.However, it is possible to hazard a comparison of the characteristic lifestyles and dietary habits of residents in the two areas by applying appropriate statistical procedures to the subject data available.
AMRs for Pizhou and Yangzhong were calculated using data from a nationwide survey and from local cancer registries, respectively.Information from death certificates combined with active confirmation at hospitals in both areas decreases the potential for misclassification of cancer deaths.Although there is no data on life expectancy in the two study areas, similar rates of mortality from causes other than cancer in Yangzhong and Pizhou support comparisons of cancer mortali-ty in the two areas as valid.
To reduce interviewer bias in the distribution of lifestyles and dietary habits between the two study areas, interviews were conducted by not fewer than five trained local staff members at five towns in each study area.
The most interesting result of the present study is that allium vegetables are consumed very much more frequently in the low risk area.Since Chinese people frequently take garlic and Welsh onion in small amounts as condiments, residents living in both the high and low risk areas can be said to consume these allium vegetables.It seems, however, that a protective effect is biologically more significant when greater quantities of allium vegetables are consumed, such as a clove of garlic.
We are not aware of formal data to the effect, but, according to private communications, the high consumption of allium vegetables in Pizhou is peculiar to this area, and the level of con-sumption in Yangzhong is more typical of that in China in general.
Many experimental studies in vivo and in vitro have shown that extracts and compounds derived from allium vegetables, especially from garlic, have a variety of protective effects against the development of cancer 11-14.22-26).Garlic is one of several vegetables which contain increased levels of selenium 27).Since allium vegetables seems to have great potential as protective agents against the development of cancer, and a decreased risk of gastric cancer for garlic consumption has been found in several case-control studies 10, 28,29 , it is suggested here that the high consumption of allium vegetables in Pizhou may be directly related to the low incidence of gastric cancer there.
In addition, people in the low risk area frequently consume raw garlic and Welsh onion, and the anticancer activity seems to be associated with heat-sensitive components (such as allicin and other thiosulfinates) as well as heat-stable components of garlic and onion 12).It is possible that raw garlic is more effective against cancer development than cooked garlic, as it retains the activity of heat-sensitive components, although few studies have compared the anticancer activity of raw and cooked garlic.It is known that Helicobacter pylori infection is associated with the risk of gastric cancer 30), and it has also been shown that Helicobacter pylori is susceptible to garlic extract 31), while heat treatment of garlic extract reduces its inhibitory or bactericidal effects on Helicobacter pylori 32).It is therefore also suggested here that the antibacterial activity of raw garlic may play a protective role in inhibiting the development of gastric cancer.
The AMR for colorectal cancer was also lower in Pizhou.A decreased risk of colon cancer for garlic consumption has been found in previous studies 33, 34) It is possible that frequent consumption of garlic may be implicated in the low AMR for colorectal cancer in Pizhou.
The higher smoking rate in Pizhou may contribute to the higher AMR for lung cancer when compared with Yangzhong.The higher AMR for lung cancer in Pizhou, despite frequent garlic consumption, is also concordant with the results of previous epidemiological studies that have failed to show any effect of garlic consumption in lowering the risk of lung cancer 17,18).
Raw vegetables, fruit, tomatoes, kidney beans and soybean products were also consumed more frequently in the low risk area.It is difficult to distinguish the protective effects of allium vegetables and these foods in an ecological study.For clarification of the protective effects of each item, analytical epidemiological studies controlled for confounding factors would provide more information.Green tea consumption has been associated with a decreased risk of gastric cancer in previous studies 35.36), while an increased risk of gastric cancer has been reported for frequent consumption of pickled vegetables 37).However, the geographical distribution of AMRs for gastric cancer in the two areas was not concordant with differences in the consumption of green tea and pickled vegetables.Moreover, consumption of cereals such as rice and wheat crackers was also different in the two areas, and it is unclear whether these cereals have any association with the risk of gastric cancer.
Food intake at high temperature, which is more common in Yangzhong, may be related to the relatively high mortality of esophageal cancer in that area 38).
Higher quality water supplies may have the potential to decrease the change to take contaminated water by carcinogens, although these were more common in Yangzhong.
In summary, an ecological study was conducted comparing environmental factors for gastric cancer in high and low risk areas in Jiangsu Province, China.Allium vegetables were consumed in the low risk area much more frequently, and raw vegetables, fruit, tomatoes, kidney beans and soybean products were consumed more frequently, in the low risk area than in the high risk area.These results suggest that frequent consumption of allium vegetables, in addition to that of other anticancer foods, may be implicated in low AMR for gastric cancer.In order to clarify the environmental and host factors associated with the risk of gastric cancer in these areas, a case-control study, a seroepidemiological study for Helicobacter pylori infection and a genetic epidemiological study on host factors are currently underway.

Figure 1 .
Figure 1.Jiangsu Province borders the Huang Sea to the east and Shanghai City to the south.Yangzhong City is located on an island in the Yangtze River in the south of Jiangsu Province, and Pizhou City is located inland to the north.
a) P values were calculated by age-adjusted Cochran -Mantel-Haenszel method .b) Consumption frequency: 3 times/week vs .less.c) Consumption frequency: frequent vs. occasionally or less.

Table 1 .
Comparison of age adjusted mortality rates (AMRs) for selected sites of cancer in Yangzhong , Pizhou, and urban and rural areas in Jiangsu Province, by sex in 1990-1992.
a) Age adjusted mortality rate , using Segi-Doll's World Population.b) Urban and rural areas with 11 .5% of total population in Jiangsu Province .

Table 2 .
Background characteristics of subjects inYangzhong (HRA : high risk area) and Pizhou (LRA : low risk area), by sex.
a) P values were calculated by age-adjusted Cochran-Mantel-Haenszel method.b)The subjects who had not graduated from elementary school .

Table 3
. Comparison of smoking, alcohol and tea consumption of residents a high risk area (HRA) and a low risk area (LRA) .bysex.a)P values were calculated by age -adjusted Cochran-Mantel-Haenszel method .The proportion of habitual tea drinking was not different in the two areas, but men in Yangzhong consumed more tea overall, and green tea consumption was more common in Yangzhong.Women consumed much less tea than men in both areas.

Table 4 .
Comparison of dietary habits and cereal consumption of residents of a high risk area (HRA) and a low risk area (LRA), by sex.
a)P values were calculated by age-adjusted Cochran-Mantel-Haenszel method .

Table 5 .
Comparison of consumption of selected foods by residents of a high risk area (HRA) and a low risk area (LRA), 10 years ago and at present.