Znt. J. Cancer: 49,381-386 (1991) 0 1991 Wiley-Liss, Inc.
Publication of the InternationalUnion Against Cancer Publication de I’Union InternationaleContre le Cancer
EFFECT OF CIGARETTE SMOKING AND ALCOHOL CONSUMPTION IN THE ETIOLOGY OF CANCERS OF THE DIGESTIVE TRACT So0 Yong CHOI’and Hiroaki WYO*
‘Laboratoryof Epidemiology, Korea Cancer Center Hospital, 215-4 Gongneung-dong,Nowon-ku, Seoul, Korea; and 2Departmentof Human Ecology, School of Medicine, University of Occupational and Environmental Health, 1-1Zseigaoka, Yuhatanishi-ku, Kitukyushu 807, Japan. This study presents the comparative patterns of risk of selected digestive tract cancers (esophagus, stomach, colon, rectum and liver) for males in relation to cigarette smoking and alcohol drinking, based on the data from case-control studies conducted in the Korea Cancer Center Hospital (KCCH). There was strong positive association between cigarette smoking and esophageal cancer, but none of the other sites was significantly related to cigarette smoking. In esophageal cancer, a dosedependent effect for cigarette smoking was observed, with the odds ratio rangingfrom I .29 for ever smoking up to I pack daily to 3.17 for smokers of more than 2 packs per day. The risk declined markedly following cessation of smoking. Cancers of the esophagus, rectum and liver were strongly related to alcohol consumption. Compared with non-drinkers, the OR for heavy drinkers was 9.14 in esophageal cancer, 4.75 in rectal cancer and 2.46 in liver cancer. In cancer of the stomach and colon, however, there was no association with alcohol drinking.
Since the early 1970s, accompanying social and economic development, cancer has become one of the major health problems in Korea because of its high mortality. In 1988, cancer of the digestive tract, especially of the stomach and liver, was the most common fatal cancer among Koreans (Korea Economic Planning Board, 1989). There are a number of epidemiological studies on cancer of the digestive tract in many countries, whereas analytical studies on cancer risk factors peculiar to Korean living environments are very scarce. Tobacco and alcohol are regarded as risk factors for various cancers. It is generally believed that cigarette smoking is positively associated with upper digestive tract cancer and that alcohol drinking increases the risk of cancer of the upper digestive tract and liver (Doll and Peto, 1981; IARC, 1986, 1988). For other cancers of the digestive tract, however, the evidence for a possible relationship with the 2 factors is still conflicting. This study presents the comparative patterns of risk of various cancers in relation to tobacco and alcohol on the basis of the data from a series of case-control studies conducted in the Korea Cancer Center Hospital of Seoul. Selected digestive tract sites were studied, i.e. esophagus, stomach, colon, rectum and liver. The objectives of the study were to evaluate the impact of cigarette smoking and alcohol drinking and to induce modifications in life-style for primary prevention of cancer. PATIENTS AND METHODS
Epidemiological information about smoking and drinking habits was collected in the KCCH (Annual Report, 1989). The KCCH functions as a cancer-specializing organization as well as a general hospital and performs both basic and clinical research on cancer. In particular, this hospital diagnoses and/or treats about 5,000 patients with cancer annually, approximately 10% of whom are new patients. The sites studied were the following (according to the 9th Revision of the International Classification of Diseases for Oncology; WHO, 1976): esophagus (ICD-0 150), stomach (151), colon (153), rectum (154), and liver (155). All the cases were confirmed by clinical, cytological and/or histopathological examination as primary cases admitted between February 1986 and March 1990.
The controls were selected from a pool of patients diagnosed as having non-cancerous diseases at the hospital. Each case was matched with 3 controls based on the year of birth (within 5 years), sex, and admission date (within 3 months). The disease sites in male control patients were stomach (45.4%), thyroid (17.2%), intestine (12.1%), kidney (8.5%), skin (5.8%) and others (ll.O%), and for females they were uterine cervix (37.9%), breast (20.2%), thyroid (18.3%), ovary (9.2%), stomach (7.0%) and others (7.4%). Cases and controls were identified through the admission records and were interviewed in the hospital. They were personally interviewed by 3 trained interviewers. The interviewers were unaware of the case-control status of the study subjects. Each study subject was interviewed according to a standard questionnaire. All questionnaires were checked for consistency and verified for accuracy of coding. When information in a questionnaire was incomplete or inconsistent, the questionnaire was sent back for correction. The questionnaire included information on socio-demographic characteristics, life-long occupational history, frequency of consumption per week of dietary items and history of disease. As regards diet, salted fish intake was categorized into 2 groups: less than once a week and more than once a week in the case of gastric cancer. In the case of cancer of the colon and rectum, meat consumption was classified into 2 groups: less than once a week and more than once a week. Patients with liver cancer and their controls were tested for serum HBsAg by radioimmunoassay. To obtain detailed information about smoking and drinking habits, we asked them to specify their age at initial exposure and their exposure period, daily consumption, etc. As for smoking habits, smokers were defined as those who had smoked at least 1 cigarette per day for at least 1 year. A patient who had stopped smoking for at least 1 year was classified as an ex-smoker. The amount of cigarettes smoked was recorded in terms of average daily consumption. Time-related variables were age at initial exposure, duration of exposure, and time since cessation. The lifetime history of alcohol drinking (usual amount and frequency) was also obtained. Non-drinkers were defined as patients who had “never or almost never” drank in the past. Drinkers were asked about specific consumption level by alcohol type, e.g. soju, beer, wine and hard liquor (whisky, gin, brandy, etc.). The favorite alcohol type was “soju” which is a commercially produced, distilled alcoholic beverage made from barley or potatoes. Its constituents are 25% alcohol, as well as citric acid, glucose, sugar, aspartame and water. Collected alcohol consumption level by type was converted into conventional units of “Hop” of soju (1 “Hop” = 90 ml). Amount of absolute alcohol consumed per year was categorized into 4 levels: (1) light ( < 8,100 ml, soju:less than 1 “Hop” a day); (2) moderate (8,100-16,200 ml:l-2 “Hop”/day), (3) medium-heavy (16,200-32,400 mk2-4 “Hop”/day), and (4) heavy ( > 32,400 m1:more than 4 “Hop”/day). For information on frequency of alcohol drinking, the drinkers were classified into “never or almost never”, “infrequent” (once a month or
Received: April 24,1991 and in revised form May 21,1991.
382
CHOI AND KAHYO
less), “occasional” (1-3 days a week) and “regular” (more than 4 days a week). The odds ratios (ORs) and their 95% confidence intervals (CIS) were computed for the smoking and alcohol drinking variables. These estimates were obtained by multiple logistic regression to control confounding factors such as age, sex and other important variables, e.g. smoking and drinking habits, and diet, using the E G R E T statistical package (1985). RESULTS
The distribution of selected digestive tract cancers and of controls according to demographic and social characteristics is shown in Table I. The average age at diagnosis for the case groups of males and females was 57.2 and 60.8 years for esophageal cancer, 50.8 and 49.2 for gastric cancer, 53.9 and 54.4 for colon cancer, 52.6 and 50.2 for rectal cancer and 49.7 and 50.9 for liver cancer, respectively. The age distribution among cases and controls was similar for 5 different sites. The distribution of marital status in the case groups was similar to that of controls for all sites except in males with esophageal cancer. Education levels of case groups were statistically different from those of controls in the case of males with esophageal, gastric and liver cancer, and of females with colon cancer. Female cases had had fewer years of schooling than male cases, and a higher proportion were widowed. In Korea, females rarely indulge in smoking and/or drinking. In this study, out of the 313 female cancer cases, there were no more than 30 smokers and 23 drinkers, while among the 939 corresponding controls there were 113 smokers and 78 drinkers. These numbers were too small to permit any meaningful analyses to be made, and the results presented here will be limited to males. The ORs for selected digestive tract cancers according to smoking habits are given in Tables 11-IV. There was a strong positive association between cigarette smoking and esophageal cancer, but none of the other sites was significantly related to cigarettes. The point estimates for cigarette smoking were somewhat above unity for cancer of the stomach and liver, and below unity for cancer of the colon and rectum, but no consistent trend was observed. The ORs of developing cancer of the esophagus were 1.11for ex-smokers and 1.93 for current smokers compared with non-smokers. There was an increase in risk both with rising duration of smoking exposure and average number of cigarette smoked per day. The OR ranged from 1.29 for those who had smoked for less than 20 years to 1.97 for those who had smoked for more than 40 years, compared with non-smokers. Based on the number of cigarettes smoked daily, the OR ranged from 1.29 for ever smoking up to a pack daily to 3.17 among smokers of more than 2 packs. The risk of esophageal cancer dropped quickly after stopping smoking. The ORs for 5 digestive tract cancers by alcohol drinking are shown in Table V-VI. The risks showed a positive trend with increasing level of alcohol use for cancer of the esophagus, rectum and Iiver. Compared with non-drinkers, the OR for heavy drinkers was 9.14 in esophageal cancer, 4.75 in rectal cancer and 2.46 in liver cancer. The risks for cancer of the esophagus, rectum and liver rose with increasing frequency of alcohol intake. The OR for regular drinkers was 4.49 in esophageal cancer, 2.10 in rectal cancer and 3.60 in liver cancer. In cancer of the stomach and colon, however, there was no association with alcohol drinking. DISCUSSION
This study presents the comparative pattern of risk of selected digestive tract cancers in relation to cigarette smoking
TABLE I - DISTRIBUTION OF DEMOGRAPHIC AND SOCIAL CHARACTERISTICSOF STUDY SUBJECTS
Site
Variable
Esophagus hiumber of subjects Age (years) -49 50-59 60 + Mean age (years) Marital status Married Widowed Others Years of education None
Male Cases
139
417
%
%
16.5 42.5 41.0 57.2
Liver
%
15.8 44.3 39.9 57.6
92.8 3.6 3.6
91.3 1.7 1.o
83.3 16.7
61.1 38.9
-
-
19.4 46.8 7-1 2 25.9 7.9 13+ 238 Number of subjects Age (years) % -49 40.5 47.4 50-59 60 12.1 Mean age (years) 50.8 Marital status 94.2 Married 1.3 Widowed 4.5 Others Years of education 9.6 None 40.4 -6 43.4 7-12 13+ 6.6 Number of subjects 63 Age (years) % -49 23.8 50-59 46.0 60 30.2 Mean age (years) 53.9 Marital status 90.5 Married 1.6 Widowed Others 7.9 Years of education 12.7 None 38.1 -6 34.9 7-12 14.3 13+ 67 Number of subjects Age (years) % -49 34.3 35.8 50-59 29.9 60 + Mean age (years) 52.6 Marital status 92.5 Married Widowed 1.5 6.0 Others Years of education 14.9 None -6 32.8 7-12 43.3 9.0 13+ Number of subjects 216 Age (years) % -49 49.1 50-59 37.5 60 13.4 Mean age (years) 49.7 Marital status 96.7 Married Widowed 1.0 2.3 Others Years of education None 5.1
15.6 36.8 36.7 10.9 714
66.7 33.7 146
33.3 55.5 5.6 5.6 438
+
Rectum
18
33.3 66.7 60.8
+
Colon
6 %
Controls
33.3 66.7 60.8
-6
Stomach
Female
Controls Cases
-6
n -71 . ._
7-12
50.0
l?+
79
%
%
%
44.9 43.0 12.1 49.7
45.2 35.6 19.2 49.2
45.2 35.7 19.1 49.1
95.0 1.8 3.2
78.1 19.9 2.0
79.2 16.2 4.6
8.1 28.4 48.8 14.7 189
26.0 45.2 28.8
21.9 38.8 35.6 3.7 153
-
22.8 47.1 30.1 53.8
51 % 31.3 31.4 37.3 54.4
28.8 35.3 35.9 54.7
86.8 1.6 11.6
78.4 17.6 4.0
74.5 20.3 5.2
11.6 30.7 38.1 19.6 201
21.6 51.0 27.4
34.8 37.3 27.9 52.4
66 % 43.9 30.3 25.8 50.2
41.2 34.6 20.3 3.9 198 % 43.4 30.8 25.8 50.3
91.0 2.5 6.5
71.2 19.7 9.1
80.8 14.1 5.1
11.9 32.8 42.3 13.0 648
25.8 48.5 22.7 3.0 44 % 38.6 56.8 4.6 50.9
22.2 39.4 24.4 4.0 132
97.2 1.2 1.6
75.0 25.0
17.3 19.3 3.4
6.3 29.9 49.5 14.3
34.1 47.7 18.2
30.7 51.1 15.9 2.3
%
%
%
56.5 32.6 10.9 48.5
-
-
-
%
%
34.1 58.0 7.9 51.0
383
SMOKING, ALCOHOL AND DIGESTIVE CANCERS IN KOREA
TABLE I1 - ODDS RATIOS FOR CANCER OF THE ESOPHAGUSAND STOMACH ACCORDING TO SMOKING STATUS (MALES) Smoking habits
Non-smoker Smoker Ex-smoker Current smoker Years of cigarette smoking 1-19 20-39 40 + Number of cigarettes uer dav " 1-20 21-40 41 + Age at start of smoking 25 + 18-24 - 17 Years since cessation Current smoker 1-4
5-9 in+
Esophagus Cases
Control
Stomach
OR'
95% CI
Cases
Controls
OR2
95% CI
15
73
1.00
Referent
40
128
1.00
Referent
15 109
57 287
1.11 1.93
0.49-2.53 1.12-2.84
24 174
93 493
0.89 1.34
0.48-1.65 0.88-2.03
6 71 47
25 215 104
1.29 1.33 1.97
0.43-3.90 0.69-2.55 1.15-3.53
39 141 18
135 393 59
1.04 1.32 1.03
0.62-1.75 0.86-2.00 0.51-2.08
86 31 7
262 72 10
1.29 1.89 3.17
0.69-2.41 0.894.01 1.06-10.24
150 43 5
478 94 14
1.05 1.57 1.25
0.70-1.59 0.93-2.65 0.40-3.94
20 82 22
68 214 62
1.43 1.52 1.23
0.66-3.12 0.81-2.86 0.54-2.82
39 121 38
104 397 85
1.29 1.04 1.60
0.77-2.17 0.68-1.58 0.92-2.77
109 10 3 2
286 24 16 18
1.00 1.07 0.78 0.32
Referent 0.49-2.37 0.20-2.99 0.08-1.31
174 8 4 12
493 40 30 23
1.oo 0.57 0.37 1.40
Referent 0.27-1.22 0.13-1.03 0.70-2.81
'Adjusted for age, marital status, education and alcohol consumption.-'Adjusted
for age, marital status, education, diet and alcohol consumption
TABLE 111- ODDS RATIOS FOR CANCER OF THE COLON AND RECTUM ACCORDING TO SMOKING STATUS (MALES) Smoking habits
Non-smoker Smoker Ex-smoker Current smoker Years of cigarette smoking 1-19 20-39 40 + Number of cigarettes uer dav 1-20 21-40 40 + Age at start of smoking 25 + 18-24 - 17 Years since cessation Current smoker 1-4 5-9 in+
Colon Cases
Controls
Rectum OR'
95% CI
Cases
Coutrols
OR'
95% CI
17
36
1.00
Referent
15
40
1.00
Referent
7 39
27 126
0.60 0.83
0.21-1.70 0.41-1.63
13 29
29 132
1.35 0.71
0.53-3.28 0.35-1.45
9 25 12
27 83 43
1.06 0.72 0.63
0.37-3.03 0.33-1.55 0.25-1.57
14 27 11
30 98 33
1.21 0.66 1.01
0.50-2.92 0.31-1.41 0.37-2.78
37 9
0.67 1.35
0.33-1.34 0.46-3.95
-
134 16 3
-
36 15 1
126 28 7
0.70 1.28 0.41
0.34-1.44 0.52-3.14 0.05-3.78
12 27 7
33 89 31
1.02 0.76 0.64
0.42-2.47 0.35-1.63 0.24-1.74
7 27 8
21 116 24
1.62 0.60 1.20
0.67-3.89 0.28-1.26 0.41-3.54
39 2
126 6 10 11
1.00 1.10 1.61
Referent 0.21-5.86
39 5 4 4
132 7 10 12
1.00 2.80 1.31 1.63
Referent 0.85-9.18 0.33-5.26 0.47-5.68
-
5
-
-
0.52-4.94
'Adjusted for age, marital status, education, diet and alcohol consumption.
and alcohol drinking, based on data from case-control studies conducted at the KCCH. The results of these studies were in agreement with other epidemiological data on cancer of the digestive tract. In this study, the association between smoking and cancer of digestive tract sites was negative except in the case of esophageal cancer. For esophageal cancer, many studies showed an effect of cigarette smoking and dose-response relationship (Tuyns et al., 1982; Vassallo et al., 1985; Ferraroni et al., 1989). The results of this study showed that there was an increase in risks with both rising duration of smoking exposure and number of cigarettes smoked per day. In particular, the risk after quitting smoking dropped quickly.
However, there was no association between smoking and the other digestive tract cancers. Stomach cancer is not generally thought of as a smoking-induced cancer. Studies of stomach cancer have not yielded such consistent results as others. Most studies showed negative associations between smoking and stomach cancer (Wynder et al., 1963; Stocks, 1970; Tuyns et al., 1982; Jedrychowski et al., 1986; Ferraroni et al., 1989), whereas in several studies the risk of stomach cancer increased with smoking (Hoey et al., 1981; Ames, 1983; Hoshino et al., 1985; Tajima and Tominaga, 1985; Hu et al., 1988; You et al., 1988). At present, it is not possible to conclude that the observed association is causal. Most reports found no substantial associations between smoking and colorectal cancer (Breslow and
384
CHOI AND KAHYO
TABLE N - ODDS RATIOS FOR CANCER OF THE LIVER ACCORDING TO SMOKING STATUS (MALES)
Smoking habits
ACCORDING TO ALCOHOL DRINKING STATUS (MALES)
Cases Controls OR' ~
Nonsmoker Smoker Ex-smoker Current Smoker Years of cigarette smoking 1-19 20-39 40 + Number of cigarettes per day 1-20 21-40 41 + Age at start of smoking 25 + 18-24 - 17 Years since cessation Current smoker 1-4 5-9 10+
TABLE VI - ODDS RATIOS FOR CANCER OF THE RECTUM AND LIVER
95% CI
Alcohol drinking habits
Cases
Controls
OR'
95% CI
~
39
120
1.00 Referent
23 154
104 424
0.65 0.35-1.19 1.01 0.65-1.57
31 128 18
121 346 61
0.71 0.40-1.28 1.00 0.64-1.58 1.85 0.41-1.76
157 18 2
420 96 12
1.18 0.75-1.84 0.62 0.32-1.22 0.51 0.10-2.59
34 121 22
86 367 75
0.84 0.37-1.93 1.35 0.67-2.71 1.28 0.59-2.81
154 14 4 5
424 46 30 28
1.00 0.76 0.43 0.44
Referent 0.31-1.89 0.15-1.26 0.11-1.82
'Adjusted for age, marital status, education, HBsAg, and alcohol consumption.
Rectum Alcohol consumption Non-drinker Light Moderate Medium-heavy Heavy Frequency of drinking No drinking InfrequentOccasional Regular Liver Alcohol consumption Non-drinker Light Moderate Medium-heavy Heavy Frequency of drinking No drinking Infrequent Occasional Regular
11 22 16 14 4
60 45 50 41 5
1.00 2.24 1.99 2.47 4.75
Referent 1.02-7.55 0.80-4.93 1.09-5.63 1.35-2.79
11 9 17 30
59 25 30 87
1.oo 1.85 2.92 2.10
Referent 0.91-6.92 1.29-6.62 1.08-4.79
34 60 72 34 16
175 223 148 69 33
1.00 1.38 2.51 2.51 2.46
Referent 0.84-2.26 1.55-4.10 1.38-4.58 1.16-5.22
34 32 62 88
175 141 213 119
1.00 1.14 1.46 3.60
Referent 0.65-2.00 0.90-2.38
'Adjusted for age, marital status, education, diet and cigarette smoking (rectum). Adjusted for age, marital status, education, HBsAg and cigarette smoking (liver).
TABLE V - ODDS RATIOS FOR CANCER OF THE ESOPHAGUS, STOMACH AND COLON ACCORDING TO ALCOHOL DRINKING STATUS (MALES) Alcohol drinking habits
Esophagus Alcohol consumption Non-drinker Light Moderate Medium-heaw Heavy Frequency of drinking No drinking Infrequent Occasional Regular Stomach Alcohol consumption Non-drinker Light Moderate Medium-heavy Heavy Frequency of drinking No drinking Infrequent Occasional Regular Colon Alcohol consumption Non-drinker Light Moderate Medium-heavy Heavy Frequency of drinking No drinking Infrequent Occasional Regular "
Cases
Controls
OR'
95% CI
14 18 55 33 19
108 107 122 56 24
1.00 1.34 4.18 5.86 9.14
Referent 0.61- 2.94 2.09- 8.38 2.78-12.35 3.79-22.07
14 7 22 96
108 44 68 197
1.00 1.58 3.61 4.49
Referent 0.56-0.50 1.63-8.02 2.37-8.50
59 51 73 31 24
160 171 210 114 56
1.00 0.82 0.90 0.75 1.19
Referent 0.53-1.26 0.59-1.37 0.45-1.25 0.67-2.13
59 27 46 106
160 100 136 318
1.00 0.72 0.86 0.91
Referent 0.42-1.21 0.54-1.37 0.62-1.33
19 14 18 10 2
45 58 50 59 7
1.00 0.63 1.09 0.99 0.75
Referent 0.29-1.38 0.46-2.55 0.43-2.30 0.15-3.65
19 4 17 23
45 31 38 75.
1.oo 0.40 1.19 0.79
Referent 0.13-1.25 0.53-2.65 0.38-1.64
'Adjusted for age, marital status, education and cigarette smoking (esophagus). Adjusted for age, marital status, education, diet and cigarette smoking (stomach and colon).
Enstrom, 1974; Wu et a/., 1987; Ferraroni et a/., 1989). It appears that nicotine may act as an indirect protective factor against colon cancer, because it stimulates bowel movements and shortens the transit time of stools, thus tending to reduce the time of exposure to carcinogenic or promoting agents in the stools (Tajima and Tominaga, 1985). However, the present study showed no significant association between smoking and cancer of colon and rectum. Moderate excesses of liver cancer have been observed in some studies (Hammond, 1966; Yu et a/., 1983; Oshima et af, 1984). Recent case-control studies have reported that liver cancer negative for serum hepatitis B virus surface antigen (HBsAg) was significantly associated with cigarette smoking even after adjustment for alcohol consumption, while such an association was not observed for patients positive for HBsAg (Lam et al., 1982; Trichopoulos et a/., 1987; Tanaka et a/., 1988). In this study, the risk did not increase liver cancer, especially among smokers who were negative for serum HBsAg. Alcohol consumption is a well-documented risk factor for esophageal cancer. In this study the risk rose with increasing level of alcohol use and frequency of alcohol exposure. It has been reported that esophageal cancer is more strongly related to consumption of distilled beverages than to wine or beer (Kon and Ikeda, 1979; Hinds et al., 1980; Tuyns et aL, 1982). It is suggested that alcohol irritates the mucosa on direct contact, which enhances the susceptibility of the tissues to carcinogenic agents. The present study showed a positive association between alcohol and liver cancer. Heavy drinkers showed an approx. 3-fold increase in risk of liver cancer as compared with non-drinkers. Most studies suggested a significant association of alcohol with liver cancer (Kon et al., 1979; Yu et a/., 1983, 1988; Hardell et a/., 1984; Oshima et al., 1984; Austin et al., 1986; Tanaka et a/., 1988) while others reported an insignificant effect of alcohol on liver cancer (Lam et al., 1982; Trichopoulos et al., 1987). Most studies generally support a positive relationship between drinking and cancer of the esophagus and liver. The other studied cancers of digestive tract sites showed negative results. Data on association between stomach cancer
SMOKING, ALCOHOL AND DIGESTIVE CANCERS IN KOREA
and consumption of alcohol are somewhat controversial. Most reports found no substantial differences in alcohol consumption (Wynder et al., 1963; Higginson, 1966; Tuyns et al., 1982; Pollack et al., 1984; You et al., 1988; Ferraroni et al., 1989). This study did not reveal any effect even after considering diet and cigarette smoking. However, some reports indicated that an elevated risk of stomach cancer was associated with consumption of alcohol, especially beer or wine (Haenszel et al., 1972; Williams et at., 1975; Hoey et al., 1981; Hu et a l , 1988). The habit of drinking on an empty stomach seems to increase the risk of developing gastric cancer (Jedrychowski et al., 1986; Hu et al., 1988), because it may lead to damage of the gastric mucosa, enhance penetration of gastric carcinogens and alter their metabolism. In rectal cancer, a statistically significant dose-response relationship was observed according to alcohol consumption. The risk of colon cancer was elevated, but was not statistically significant. Evidence for a role of alcohol in cancer of the colon and rectum is still conflicting and inconsistent. The possible role of alcohol has been noteworthy in some studies in that beer drinking has been related to colorectal cancer, particularly rectal cancer (Wynder and Shigematsu, 1967; Breslow et al., 1974; Pollack et al., 1984; Kabat et al., 1986; Klatsky et al., 1988). However, no mechanism has been suggested for the carcinogenic action of beer in the causation of colorectal cancer. Moderate alcohol intake decreases cholesterol saturation of bile by increasing bile acid concentration, which may play a role in the formation and metabolism of fecal carcinogens (Thorton et a[., 1983). Beer might interact with the diet either to influence the fecal flora of the gut, or the steroid concentration in the gut, or alter the gut transit time (Zaridze, 1983; Kabat et al., 1986). Soju, made of
385
distilled barley and potatoes, is the most common alcoholic drink in Korea. Most of the subjects studied drank beer infrequently. This study did not consider beer consumption. However, it is difficult to dismiss the possibility of a relation between ethyl alcohol and colorectal cancer, especially rectal cancer. One could hypothesize that the risk may be associated with the type of alcohol to which humans are exposed. The various components of whiskey, beer, wine and gin may work in conjunction with alcohol to produce cancer. In summary, esophageal cancer was found to be significantly related to smoking and alcohol drinking. None of the other digestive tract cancers was associated with smoking. There was an elevated risk of cancer of the liver and rectum among alcohol consumers. The present findings could have important public health implications. Although the results of epidemiological studies of smoking and alcohol, and cancer of the stomach, liver, colon and rectum especially remain conflicting and inconsistent, in defining policies for prevention, it cannot be overlooked that cigarette smoking and alcohol consumption do appear to be risk factors for digestive tract cancers. It is suggested that a more widely and systematically conducted, comparative casecontrol study could be effective in identifying common, inverse or independent risk factors for the studied cancer. ACKNOWLEDGEMENTS
We thank Dr. Y.H. Lee, Seoul National University, for helpful comments and Mr. H. Won and Mr. K.H. Kim, KCCH, for their help in this work.
REFERENCES H., HIRAYAMA, T., ARIMOTO, H., MARUYAMA, K., KITAOKA, AMES,R.G., Gastric cancer and coal mine dust exposure: a case- HOSHINO, H., YAMADA, T., HIROTA,T., WATANABE, S., TANAKA, M., SUZUKI,S. control study. Cancer, 52,1346-1350 (1983). and AIHARA,K., Gastric cancer risk factors: a case-control study based Annual Report of Korea Cancer Center Hospital. KCCH, Seoul (1989). on medical records.Jap. J. Cancer Res., 76,846850 (1985). AUSTIN,H., DELZELL,E., GRUFFERMAN, S., LEVINE,R., MORRISON, A.S., STOLLEY, P.D. and COLE,P., A case-control study of hepatocellu- Hu, J., ZHANG,S., JIA, E., WANG,Q., LIU, S., LIU, Y., Wu, Y . and lar carcinoma and the hepatitis B virus, cigarette smoking and alcohol CHENG,Y . , Diet and cancer of the stomach: a case-control study in China. Ini. J. Cancer, 41,331-335 (1988). consumption. Cancer Res., 46,962-966 (1986). BRESLOW, N.E. and ENSTROM, J.E., Geographic correlations between MRCMonographs on the evaluation of the carcinogenic risk of chemicals cancer mortality rates and alcohol-tobacco consumption in the United to humans: tobacco smoking, Vol. 38, IARC, Lyon (1986). States. J. nut. CancerInst., 53,631-639 (1974). M R C Monographs on the Evaluation of Carcinogenic Risks to Humans: DOLL,R. and PETO,R., The causes of cancer: quantitative estimates of Alcohol drinking, Vol. 44, IARC, Lyon (1988). avoidable risks of cancer in the United States today. J. nut. Cancerlnst., JEDRYCHOWSKI, W., WAHRENDORF, J., POPIELA,T. and RACHTAM, J., 6,1193-1308 (1981). A case-control study of dietary factors and stomach cancer risk in Poland. Int. J. Cancer, 37,837-842 (1986). EGRET STATISTICAL PACKAGE, Statistics and Epidemiology Research Corp., Seattle, WA (1985). KABAT,G.C., HOWSON,C.P. and WYNDER,E.L., Beer consumption FERRARONI,M., NEGRI, E., VECCHIA,C.L., D’AVANZO,B. and and rectal cancer. Int. J. Epidemiol., 15,494-501 (1986). S., Socioeconomic indicators, tobacco and alcohol in the KLATSKY, FRANCESCHI, A.L., ARMSTRONG, M.A. and FRIEDMAN, G.D., The relationaetiology of digestive tract neoplasms. Int. J. Epidemiol., 18, 556-562 ship of alcoholic beverage use to colon and rectal cancer. Amer. J. (1989). Epidemiol., 128,1007-1015 (1988). HAENSZEL, W., KURIHARA, M., SEGI,M. and LEE, R.K.C., Stomach KON, S. and IKEDA,M., Correlation between cancer mortality and cancer among Japanese in Hawaii. J. nat. Cancer Insr., 49, 969-988 alcoholic beverage in Japan. Brit. J. Currcer, 40,449-455 (1979). (1972). KOREA ECONOMIC PLANNING BOARD.Annual report on the causes of HAMMOND, E.C., Smoking in relation to the death rates of one million death. Statistics, 1988. Korea Economic Planning Board, Seoul (1989). men and women. Nut. CancerInst. Monogr., 19,127-204 (1966). B.E., Hepatitis HARDELL,L., BENGTSSON, N.O., JONSSON,U., ERIKSSON,S. and LAM,K.C., Yu, M.C., LEUNG,J.W.C. and HENDERSON, LARSSON,L.G., Aetiological aspects on primary liver cancer with B virus and cigarette smoking: risk factors for hepatocellular carcinoma in Hong Kong. Cancer Res., 42,5246-5248 (1982). special regard to alcohol, organic solvents and acute intermittent porphyria; an epidemiological investigation. Brit. J. Cancer, 50, 389OSHIMA,A., TSUKUMA, H., HIYAMA, T., FUJIMOTO, I., YAMANO, H. and 397 (1984). TANAKA,M., Follow-up study of HBsAg-positive blood donors with special reference to effect of drinking and smoking on development of HIGGINSON, J., Etiological factors in gastrointestinal cancer in man. J. liver cancer. Int. J. Canceq 34,775-779 (1984). nat. Cancer Inst., 37,527-545 (1966). E.S., NOMURA,A.M.Y., HEILBRUM, L.K., STEMMERMANN, HINDS,M.W., KOLONEL, L.N., LEE,J. and HIROHATA, T., Associations POLLACK, between cancer incidence and alcoholicigarette consumption among G.N. and GREEN,S.B., Prospective study of alcohol consumption and cancer. N. Engl. J. Med., 310,617-621 (1984). five ethnic groups in Hawaii. Brit. J. Cancer, 41,929-940 (1980). HOEY,J., MONTVERNAY, C. and LAMBERT, R., Wine and tobacco: risk STOCKS,P., Cancer mortality in relation to national consumption of cigarettes, soil and fuel, tea and coffee. Brit. J. Cancer, 24, 215-225 factors for gastric cancer in France. Amer. J. Epidemiol., 113,668-674 (1970). (1981).
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TAJIMA,K. and TOMINAGA, S., Dietary habits and gastro-intestinal cancers: a comparative case-control study of stomach and large intestinal cancer in Nagoya, Japan. Jap. J. Cancer Res., 76, 705-716 (1985). TANAKA, K., HIROHATA, T. and TAKESHITA, S., Blood transfusion, alcohol consumption, and cigarette smoking in causation of hepatocellular carcinoma: a case-control study in Fukuoka, Japan. Jap. J. Cancer Res., 79,1075-1082 (1988). THORTON,J., SYMES,C. and HEATON,K., Moderate alcohol intake reduces bile cholesterol saturation and raises HDL cholesterol. Lancet, 11,819 (1983). TRICHOPOULOS, D., DAY,N.E., KAKLAMANI, E., TZONOU, A., Mufioz, N., ZAVITSANOS, X., KOUMANTAKI, Y. and TRICHOPOULOU, A., Hepatitis B virus, tobacco smoking and ethanol consumption in the etiology of hepatocellular carcinoma. Int. J. Cancer, 39,45-49 (1987). TUYNS, A.T., P~QUIGNOT, G., GIGNOUX, M. and VALLA,A., Cancers of the digestive tract, alcohol and tobacco. Int. J. Cancer, 30,9-11 (1982). VASSALLO, A,, CORREA, P., STEFANI, E.D., CENDAN, M., ZAVALA, D., CHEN,V., CARZOGLIO, J. and DENEO-PELLEGRINI, H., Esophageal cancer in Uruguay: a case-control study. J. nat. Cancer Inst., 75, 1005-1009 (1985). WILLIAMS, R.H.P., SMITH,J., COLE,T.J. and CRAVEN, J.L., Dietary and smoking habits in gastric cancer: a detailed study of 64 cases and controls. Gut, 16,843 (1975).
WORLDHEALTHORGANIZATION. International Class@cation of Diseases for Oncology. WHO, Geneva (1976). Wu, A.H., PAGANINI-HILL, A. and Ross, R.K., Alcohol, physical activity and other risk factors for colorectal cancer; a prospective study. Brit. J. Cancer, 55,687-694 (1987). WYNDER,E.L., KMET,J., DUNGAL, N. and SEGI,M., An epidemiological investigation of gastric cancer. Cancer, 16, 1461-1496 (1963). WYNDER, E.L. and SHIGEMATSU, T., Environmental factors of cancer of the colon and rectum. Cancer, 20,1520-1561 (1967). You, W.C.,BLOT,W.T., CHANG,Y.S.,ERSHOW,A.G.,YANG, Z.T.,AN, Q., Xu, G.W., FRAUMENI, J.F. and WANG,T.G., Diet and high risk of stomach cancer in Shandong, China. Cancer Res., 48, 3518-3523 (1988). Yu, H., HARRIS,R.E., KABAT,G.C. and WYNDER,E.L. Cigarette smoking, alcohol consumption and primary liver cancer: a case-control study in the USA. Int. J. Cancer, 42,325-328 (1988). Yu, M.C., MACK,T., HANISCH, R., PETERS,R.L., HENDERSON, B.E. and PIKE, M.C., Hepatitis, alcohol consumption, cigarette smoking and hepatocellular carcinoma in Los Angeles. Cancer Res., 43, 60776079 (1983). ZARIDZE, D.G., Environmental etiology of large-bowl cancer. (Editorial). J. nat. Cancer Inst., 70,389-400 (1983).
Publication of the InternationalUnion Against Cancer Publication de I’Union InternationaleContre le Cancer
EFFECT OF CIGARETTE SMOKING AND ALCOHOL CONSUMPTION IN THE ETIOLOGY OF CANCERS OF THE DIGESTIVE TRACT So0 Yong CHOI’and Hiroaki WYO*
‘Laboratoryof Epidemiology, Korea Cancer Center Hospital, 215-4 Gongneung-dong,Nowon-ku, Seoul, Korea; and 2Departmentof Human Ecology, School of Medicine, University of Occupational and Environmental Health, 1-1Zseigaoka, Yuhatanishi-ku, Kitukyushu 807, Japan. This study presents the comparative patterns of risk of selected digestive tract cancers (esophagus, stomach, colon, rectum and liver) for males in relation to cigarette smoking and alcohol drinking, based on the data from case-control studies conducted in the Korea Cancer Center Hospital (KCCH). There was strong positive association between cigarette smoking and esophageal cancer, but none of the other sites was significantly related to cigarette smoking. In esophageal cancer, a dosedependent effect for cigarette smoking was observed, with the odds ratio rangingfrom I .29 for ever smoking up to I pack daily to 3.17 for smokers of more than 2 packs per day. The risk declined markedly following cessation of smoking. Cancers of the esophagus, rectum and liver were strongly related to alcohol consumption. Compared with non-drinkers, the OR for heavy drinkers was 9.14 in esophageal cancer, 4.75 in rectal cancer and 2.46 in liver cancer. In cancer of the stomach and colon, however, there was no association with alcohol drinking.
Since the early 1970s, accompanying social and economic development, cancer has become one of the major health problems in Korea because of its high mortality. In 1988, cancer of the digestive tract, especially of the stomach and liver, was the most common fatal cancer among Koreans (Korea Economic Planning Board, 1989). There are a number of epidemiological studies on cancer of the digestive tract in many countries, whereas analytical studies on cancer risk factors peculiar to Korean living environments are very scarce. Tobacco and alcohol are regarded as risk factors for various cancers. It is generally believed that cigarette smoking is positively associated with upper digestive tract cancer and that alcohol drinking increases the risk of cancer of the upper digestive tract and liver (Doll and Peto, 1981; IARC, 1986, 1988). For other cancers of the digestive tract, however, the evidence for a possible relationship with the 2 factors is still conflicting. This study presents the comparative patterns of risk of various cancers in relation to tobacco and alcohol on the basis of the data from a series of case-control studies conducted in the Korea Cancer Center Hospital of Seoul. Selected digestive tract sites were studied, i.e. esophagus, stomach, colon, rectum and liver. The objectives of the study were to evaluate the impact of cigarette smoking and alcohol drinking and to induce modifications in life-style for primary prevention of cancer. PATIENTS AND METHODS
Epidemiological information about smoking and drinking habits was collected in the KCCH (Annual Report, 1989). The KCCH functions as a cancer-specializing organization as well as a general hospital and performs both basic and clinical research on cancer. In particular, this hospital diagnoses and/or treats about 5,000 patients with cancer annually, approximately 10% of whom are new patients. The sites studied were the following (according to the 9th Revision of the International Classification of Diseases for Oncology; WHO, 1976): esophagus (ICD-0 150), stomach (151), colon (153), rectum (154), and liver (155). All the cases were confirmed by clinical, cytological and/or histopathological examination as primary cases admitted between February 1986 and March 1990.
The controls were selected from a pool of patients diagnosed as having non-cancerous diseases at the hospital. Each case was matched with 3 controls based on the year of birth (within 5 years), sex, and admission date (within 3 months). The disease sites in male control patients were stomach (45.4%), thyroid (17.2%), intestine (12.1%), kidney (8.5%), skin (5.8%) and others (ll.O%), and for females they were uterine cervix (37.9%), breast (20.2%), thyroid (18.3%), ovary (9.2%), stomach (7.0%) and others (7.4%). Cases and controls were identified through the admission records and were interviewed in the hospital. They were personally interviewed by 3 trained interviewers. The interviewers were unaware of the case-control status of the study subjects. Each study subject was interviewed according to a standard questionnaire. All questionnaires were checked for consistency and verified for accuracy of coding. When information in a questionnaire was incomplete or inconsistent, the questionnaire was sent back for correction. The questionnaire included information on socio-demographic characteristics, life-long occupational history, frequency of consumption per week of dietary items and history of disease. As regards diet, salted fish intake was categorized into 2 groups: less than once a week and more than once a week in the case of gastric cancer. In the case of cancer of the colon and rectum, meat consumption was classified into 2 groups: less than once a week and more than once a week. Patients with liver cancer and their controls were tested for serum HBsAg by radioimmunoassay. To obtain detailed information about smoking and drinking habits, we asked them to specify their age at initial exposure and their exposure period, daily consumption, etc. As for smoking habits, smokers were defined as those who had smoked at least 1 cigarette per day for at least 1 year. A patient who had stopped smoking for at least 1 year was classified as an ex-smoker. The amount of cigarettes smoked was recorded in terms of average daily consumption. Time-related variables were age at initial exposure, duration of exposure, and time since cessation. The lifetime history of alcohol drinking (usual amount and frequency) was also obtained. Non-drinkers were defined as patients who had “never or almost never” drank in the past. Drinkers were asked about specific consumption level by alcohol type, e.g. soju, beer, wine and hard liquor (whisky, gin, brandy, etc.). The favorite alcohol type was “soju” which is a commercially produced, distilled alcoholic beverage made from barley or potatoes. Its constituents are 25% alcohol, as well as citric acid, glucose, sugar, aspartame and water. Collected alcohol consumption level by type was converted into conventional units of “Hop” of soju (1 “Hop” = 90 ml). Amount of absolute alcohol consumed per year was categorized into 4 levels: (1) light ( < 8,100 ml, soju:less than 1 “Hop” a day); (2) moderate (8,100-16,200 ml:l-2 “Hop”/day), (3) medium-heavy (16,200-32,400 mk2-4 “Hop”/day), and (4) heavy ( > 32,400 m1:more than 4 “Hop”/day). For information on frequency of alcohol drinking, the drinkers were classified into “never or almost never”, “infrequent” (once a month or
Received: April 24,1991 and in revised form May 21,1991.
382
CHOI AND KAHYO
less), “occasional” (1-3 days a week) and “regular” (more than 4 days a week). The odds ratios (ORs) and their 95% confidence intervals (CIS) were computed for the smoking and alcohol drinking variables. These estimates were obtained by multiple logistic regression to control confounding factors such as age, sex and other important variables, e.g. smoking and drinking habits, and diet, using the E G R E T statistical package (1985). RESULTS
The distribution of selected digestive tract cancers and of controls according to demographic and social characteristics is shown in Table I. The average age at diagnosis for the case groups of males and females was 57.2 and 60.8 years for esophageal cancer, 50.8 and 49.2 for gastric cancer, 53.9 and 54.4 for colon cancer, 52.6 and 50.2 for rectal cancer and 49.7 and 50.9 for liver cancer, respectively. The age distribution among cases and controls was similar for 5 different sites. The distribution of marital status in the case groups was similar to that of controls for all sites except in males with esophageal cancer. Education levels of case groups were statistically different from those of controls in the case of males with esophageal, gastric and liver cancer, and of females with colon cancer. Female cases had had fewer years of schooling than male cases, and a higher proportion were widowed. In Korea, females rarely indulge in smoking and/or drinking. In this study, out of the 313 female cancer cases, there were no more than 30 smokers and 23 drinkers, while among the 939 corresponding controls there were 113 smokers and 78 drinkers. These numbers were too small to permit any meaningful analyses to be made, and the results presented here will be limited to males. The ORs for selected digestive tract cancers according to smoking habits are given in Tables 11-IV. There was a strong positive association between cigarette smoking and esophageal cancer, but none of the other sites was significantly related to cigarettes. The point estimates for cigarette smoking were somewhat above unity for cancer of the stomach and liver, and below unity for cancer of the colon and rectum, but no consistent trend was observed. The ORs of developing cancer of the esophagus were 1.11for ex-smokers and 1.93 for current smokers compared with non-smokers. There was an increase in risk both with rising duration of smoking exposure and average number of cigarette smoked per day. The OR ranged from 1.29 for those who had smoked for less than 20 years to 1.97 for those who had smoked for more than 40 years, compared with non-smokers. Based on the number of cigarettes smoked daily, the OR ranged from 1.29 for ever smoking up to a pack daily to 3.17 among smokers of more than 2 packs. The risk of esophageal cancer dropped quickly after stopping smoking. The ORs for 5 digestive tract cancers by alcohol drinking are shown in Table V-VI. The risks showed a positive trend with increasing level of alcohol use for cancer of the esophagus, rectum and Iiver. Compared with non-drinkers, the OR for heavy drinkers was 9.14 in esophageal cancer, 4.75 in rectal cancer and 2.46 in liver cancer. The risks for cancer of the esophagus, rectum and liver rose with increasing frequency of alcohol intake. The OR for regular drinkers was 4.49 in esophageal cancer, 2.10 in rectal cancer and 3.60 in liver cancer. In cancer of the stomach and colon, however, there was no association with alcohol drinking. DISCUSSION
This study presents the comparative pattern of risk of selected digestive tract cancers in relation to cigarette smoking
TABLE I - DISTRIBUTION OF DEMOGRAPHIC AND SOCIAL CHARACTERISTICSOF STUDY SUBJECTS
Site
Variable
Esophagus hiumber of subjects Age (years) -49 50-59 60 + Mean age (years) Marital status Married Widowed Others Years of education None
Male Cases
139
417
%
%
16.5 42.5 41.0 57.2
Liver
%
15.8 44.3 39.9 57.6
92.8 3.6 3.6
91.3 1.7 1.o
83.3 16.7
61.1 38.9
-
-
19.4 46.8 7-1 2 25.9 7.9 13+ 238 Number of subjects Age (years) % -49 40.5 47.4 50-59 60 12.1 Mean age (years) 50.8 Marital status 94.2 Married 1.3 Widowed 4.5 Others Years of education 9.6 None 40.4 -6 43.4 7-12 13+ 6.6 Number of subjects 63 Age (years) % -49 23.8 50-59 46.0 60 30.2 Mean age (years) 53.9 Marital status 90.5 Married 1.6 Widowed Others 7.9 Years of education 12.7 None 38.1 -6 34.9 7-12 14.3 13+ 67 Number of subjects Age (years) % -49 34.3 35.8 50-59 29.9 60 + Mean age (years) 52.6 Marital status 92.5 Married Widowed 1.5 6.0 Others Years of education 14.9 None -6 32.8 7-12 43.3 9.0 13+ Number of subjects 216 Age (years) % -49 49.1 50-59 37.5 60 13.4 Mean age (years) 49.7 Marital status 96.7 Married Widowed 1.0 2.3 Others Years of education None 5.1
15.6 36.8 36.7 10.9 714
66.7 33.7 146
33.3 55.5 5.6 5.6 438
+
Rectum
18
33.3 66.7 60.8
+
Colon
6 %
Controls
33.3 66.7 60.8
-6
Stomach
Female
Controls Cases
-6
n -71 . ._
7-12
50.0
l?+
79
%
%
%
44.9 43.0 12.1 49.7
45.2 35.6 19.2 49.2
45.2 35.7 19.1 49.1
95.0 1.8 3.2
78.1 19.9 2.0
79.2 16.2 4.6
8.1 28.4 48.8 14.7 189
26.0 45.2 28.8
21.9 38.8 35.6 3.7 153
-
22.8 47.1 30.1 53.8
51 % 31.3 31.4 37.3 54.4
28.8 35.3 35.9 54.7
86.8 1.6 11.6
78.4 17.6 4.0
74.5 20.3 5.2
11.6 30.7 38.1 19.6 201
21.6 51.0 27.4
34.8 37.3 27.9 52.4
66 % 43.9 30.3 25.8 50.2
41.2 34.6 20.3 3.9 198 % 43.4 30.8 25.8 50.3
91.0 2.5 6.5
71.2 19.7 9.1
80.8 14.1 5.1
11.9 32.8 42.3 13.0 648
25.8 48.5 22.7 3.0 44 % 38.6 56.8 4.6 50.9
22.2 39.4 24.4 4.0 132
97.2 1.2 1.6
75.0 25.0
17.3 19.3 3.4
6.3 29.9 49.5 14.3
34.1 47.7 18.2
30.7 51.1 15.9 2.3
%
%
%
56.5 32.6 10.9 48.5
-
-
-
%
%
34.1 58.0 7.9 51.0
383
SMOKING, ALCOHOL AND DIGESTIVE CANCERS IN KOREA
TABLE I1 - ODDS RATIOS FOR CANCER OF THE ESOPHAGUSAND STOMACH ACCORDING TO SMOKING STATUS (MALES) Smoking habits
Non-smoker Smoker Ex-smoker Current smoker Years of cigarette smoking 1-19 20-39 40 + Number of cigarettes uer dav " 1-20 21-40 41 + Age at start of smoking 25 + 18-24 - 17 Years since cessation Current smoker 1-4
5-9 in+
Esophagus Cases
Control
Stomach
OR'
95% CI
Cases
Controls
OR2
95% CI
15
73
1.00
Referent
40
128
1.00
Referent
15 109
57 287
1.11 1.93
0.49-2.53 1.12-2.84
24 174
93 493
0.89 1.34
0.48-1.65 0.88-2.03
6 71 47
25 215 104
1.29 1.33 1.97
0.43-3.90 0.69-2.55 1.15-3.53
39 141 18
135 393 59
1.04 1.32 1.03
0.62-1.75 0.86-2.00 0.51-2.08
86 31 7
262 72 10
1.29 1.89 3.17
0.69-2.41 0.894.01 1.06-10.24
150 43 5
478 94 14
1.05 1.57 1.25
0.70-1.59 0.93-2.65 0.40-3.94
20 82 22
68 214 62
1.43 1.52 1.23
0.66-3.12 0.81-2.86 0.54-2.82
39 121 38
104 397 85
1.29 1.04 1.60
0.77-2.17 0.68-1.58 0.92-2.77
109 10 3 2
286 24 16 18
1.00 1.07 0.78 0.32
Referent 0.49-2.37 0.20-2.99 0.08-1.31
174 8 4 12
493 40 30 23
1.oo 0.57 0.37 1.40
Referent 0.27-1.22 0.13-1.03 0.70-2.81
'Adjusted for age, marital status, education and alcohol consumption.-'Adjusted
for age, marital status, education, diet and alcohol consumption
TABLE 111- ODDS RATIOS FOR CANCER OF THE COLON AND RECTUM ACCORDING TO SMOKING STATUS (MALES) Smoking habits
Non-smoker Smoker Ex-smoker Current smoker Years of cigarette smoking 1-19 20-39 40 + Number of cigarettes uer dav 1-20 21-40 40 + Age at start of smoking 25 + 18-24 - 17 Years since cessation Current smoker 1-4 5-9 in+
Colon Cases
Controls
Rectum OR'
95% CI
Cases
Coutrols
OR'
95% CI
17
36
1.00
Referent
15
40
1.00
Referent
7 39
27 126
0.60 0.83
0.21-1.70 0.41-1.63
13 29
29 132
1.35 0.71
0.53-3.28 0.35-1.45
9 25 12
27 83 43
1.06 0.72 0.63
0.37-3.03 0.33-1.55 0.25-1.57
14 27 11
30 98 33
1.21 0.66 1.01
0.50-2.92 0.31-1.41 0.37-2.78
37 9
0.67 1.35
0.33-1.34 0.46-3.95
-
134 16 3
-
36 15 1
126 28 7
0.70 1.28 0.41
0.34-1.44 0.52-3.14 0.05-3.78
12 27 7
33 89 31
1.02 0.76 0.64
0.42-2.47 0.35-1.63 0.24-1.74
7 27 8
21 116 24
1.62 0.60 1.20
0.67-3.89 0.28-1.26 0.41-3.54
39 2
126 6 10 11
1.00 1.10 1.61
Referent 0.21-5.86
39 5 4 4
132 7 10 12
1.00 2.80 1.31 1.63
Referent 0.85-9.18 0.33-5.26 0.47-5.68
-
5
-
-
0.52-4.94
'Adjusted for age, marital status, education, diet and alcohol consumption.
and alcohol drinking, based on data from case-control studies conducted at the KCCH. The results of these studies were in agreement with other epidemiological data on cancer of the digestive tract. In this study, the association between smoking and cancer of digestive tract sites was negative except in the case of esophageal cancer. For esophageal cancer, many studies showed an effect of cigarette smoking and dose-response relationship (Tuyns et al., 1982; Vassallo et al., 1985; Ferraroni et al., 1989). The results of this study showed that there was an increase in risks with both rising duration of smoking exposure and number of cigarettes smoked per day. In particular, the risk after quitting smoking dropped quickly.
However, there was no association between smoking and the other digestive tract cancers. Stomach cancer is not generally thought of as a smoking-induced cancer. Studies of stomach cancer have not yielded such consistent results as others. Most studies showed negative associations between smoking and stomach cancer (Wynder et al., 1963; Stocks, 1970; Tuyns et al., 1982; Jedrychowski et al., 1986; Ferraroni et al., 1989), whereas in several studies the risk of stomach cancer increased with smoking (Hoey et al., 1981; Ames, 1983; Hoshino et al., 1985; Tajima and Tominaga, 1985; Hu et al., 1988; You et al., 1988). At present, it is not possible to conclude that the observed association is causal. Most reports found no substantial associations between smoking and colorectal cancer (Breslow and
384
CHOI AND KAHYO
TABLE N - ODDS RATIOS FOR CANCER OF THE LIVER ACCORDING TO SMOKING STATUS (MALES)
Smoking habits
ACCORDING TO ALCOHOL DRINKING STATUS (MALES)
Cases Controls OR' ~
Nonsmoker Smoker Ex-smoker Current Smoker Years of cigarette smoking 1-19 20-39 40 + Number of cigarettes per day 1-20 21-40 41 + Age at start of smoking 25 + 18-24 - 17 Years since cessation Current smoker 1-4 5-9 10+
TABLE VI - ODDS RATIOS FOR CANCER OF THE RECTUM AND LIVER
95% CI
Alcohol drinking habits
Cases
Controls
OR'
95% CI
~
39
120
1.00 Referent
23 154
104 424
0.65 0.35-1.19 1.01 0.65-1.57
31 128 18
121 346 61
0.71 0.40-1.28 1.00 0.64-1.58 1.85 0.41-1.76
157 18 2
420 96 12
1.18 0.75-1.84 0.62 0.32-1.22 0.51 0.10-2.59
34 121 22
86 367 75
0.84 0.37-1.93 1.35 0.67-2.71 1.28 0.59-2.81
154 14 4 5
424 46 30 28
1.00 0.76 0.43 0.44
Referent 0.31-1.89 0.15-1.26 0.11-1.82
'Adjusted for age, marital status, education, HBsAg, and alcohol consumption.
Rectum Alcohol consumption Non-drinker Light Moderate Medium-heavy Heavy Frequency of drinking No drinking InfrequentOccasional Regular Liver Alcohol consumption Non-drinker Light Moderate Medium-heavy Heavy Frequency of drinking No drinking Infrequent Occasional Regular
11 22 16 14 4
60 45 50 41 5
1.00 2.24 1.99 2.47 4.75
Referent 1.02-7.55 0.80-4.93 1.09-5.63 1.35-2.79
11 9 17 30
59 25 30 87
1.oo 1.85 2.92 2.10
Referent 0.91-6.92 1.29-6.62 1.08-4.79
34 60 72 34 16
175 223 148 69 33
1.00 1.38 2.51 2.51 2.46
Referent 0.84-2.26 1.55-4.10 1.38-4.58 1.16-5.22
34 32 62 88
175 141 213 119
1.00 1.14 1.46 3.60
Referent 0.65-2.00 0.90-2.38
'Adjusted for age, marital status, education, diet and cigarette smoking (rectum). Adjusted for age, marital status, education, HBsAg and cigarette smoking (liver).
TABLE V - ODDS RATIOS FOR CANCER OF THE ESOPHAGUS, STOMACH AND COLON ACCORDING TO ALCOHOL DRINKING STATUS (MALES) Alcohol drinking habits
Esophagus Alcohol consumption Non-drinker Light Moderate Medium-heaw Heavy Frequency of drinking No drinking Infrequent Occasional Regular Stomach Alcohol consumption Non-drinker Light Moderate Medium-heavy Heavy Frequency of drinking No drinking Infrequent Occasional Regular Colon Alcohol consumption Non-drinker Light Moderate Medium-heavy Heavy Frequency of drinking No drinking Infrequent Occasional Regular "
Cases
Controls
OR'
95% CI
14 18 55 33 19
108 107 122 56 24
1.00 1.34 4.18 5.86 9.14
Referent 0.61- 2.94 2.09- 8.38 2.78-12.35 3.79-22.07
14 7 22 96
108 44 68 197
1.00 1.58 3.61 4.49
Referent 0.56-0.50 1.63-8.02 2.37-8.50
59 51 73 31 24
160 171 210 114 56
1.00 0.82 0.90 0.75 1.19
Referent 0.53-1.26 0.59-1.37 0.45-1.25 0.67-2.13
59 27 46 106
160 100 136 318
1.00 0.72 0.86 0.91
Referent 0.42-1.21 0.54-1.37 0.62-1.33
19 14 18 10 2
45 58 50 59 7
1.00 0.63 1.09 0.99 0.75
Referent 0.29-1.38 0.46-2.55 0.43-2.30 0.15-3.65
19 4 17 23
45 31 38 75.
1.oo 0.40 1.19 0.79
Referent 0.13-1.25 0.53-2.65 0.38-1.64
'Adjusted for age, marital status, education and cigarette smoking (esophagus). Adjusted for age, marital status, education, diet and cigarette smoking (stomach and colon).
Enstrom, 1974; Wu et a/., 1987; Ferraroni et a/., 1989). It appears that nicotine may act as an indirect protective factor against colon cancer, because it stimulates bowel movements and shortens the transit time of stools, thus tending to reduce the time of exposure to carcinogenic or promoting agents in the stools (Tajima and Tominaga, 1985). However, the present study showed no significant association between smoking and cancer of colon and rectum. Moderate excesses of liver cancer have been observed in some studies (Hammond, 1966; Yu et a/., 1983; Oshima et af, 1984). Recent case-control studies have reported that liver cancer negative for serum hepatitis B virus surface antigen (HBsAg) was significantly associated with cigarette smoking even after adjustment for alcohol consumption, while such an association was not observed for patients positive for HBsAg (Lam et al., 1982; Trichopoulos et a/., 1987; Tanaka et a/., 1988). In this study, the risk did not increase liver cancer, especially among smokers who were negative for serum HBsAg. Alcohol consumption is a well-documented risk factor for esophageal cancer. In this study the risk rose with increasing level of alcohol use and frequency of alcohol exposure. It has been reported that esophageal cancer is more strongly related to consumption of distilled beverages than to wine or beer (Kon and Ikeda, 1979; Hinds et al., 1980; Tuyns et aL, 1982). It is suggested that alcohol irritates the mucosa on direct contact, which enhances the susceptibility of the tissues to carcinogenic agents. The present study showed a positive association between alcohol and liver cancer. Heavy drinkers showed an approx. 3-fold increase in risk of liver cancer as compared with non-drinkers. Most studies suggested a significant association of alcohol with liver cancer (Kon et al., 1979; Yu et a/., 1983, 1988; Hardell et a/., 1984; Oshima et al., 1984; Austin et al., 1986; Tanaka et a/., 1988) while others reported an insignificant effect of alcohol on liver cancer (Lam et al., 1982; Trichopoulos et al., 1987). Most studies generally support a positive relationship between drinking and cancer of the esophagus and liver. The other studied cancers of digestive tract sites showed negative results. Data on association between stomach cancer
SMOKING, ALCOHOL AND DIGESTIVE CANCERS IN KOREA
and consumption of alcohol are somewhat controversial. Most reports found no substantial differences in alcohol consumption (Wynder et al., 1963; Higginson, 1966; Tuyns et al., 1982; Pollack et al., 1984; You et al., 1988; Ferraroni et al., 1989). This study did not reveal any effect even after considering diet and cigarette smoking. However, some reports indicated that an elevated risk of stomach cancer was associated with consumption of alcohol, especially beer or wine (Haenszel et al., 1972; Williams et at., 1975; Hoey et al., 1981; Hu et a l , 1988). The habit of drinking on an empty stomach seems to increase the risk of developing gastric cancer (Jedrychowski et al., 1986; Hu et al., 1988), because it may lead to damage of the gastric mucosa, enhance penetration of gastric carcinogens and alter their metabolism. In rectal cancer, a statistically significant dose-response relationship was observed according to alcohol consumption. The risk of colon cancer was elevated, but was not statistically significant. Evidence for a role of alcohol in cancer of the colon and rectum is still conflicting and inconsistent. The possible role of alcohol has been noteworthy in some studies in that beer drinking has been related to colorectal cancer, particularly rectal cancer (Wynder and Shigematsu, 1967; Breslow et al., 1974; Pollack et al., 1984; Kabat et al., 1986; Klatsky et al., 1988). However, no mechanism has been suggested for the carcinogenic action of beer in the causation of colorectal cancer. Moderate alcohol intake decreases cholesterol saturation of bile by increasing bile acid concentration, which may play a role in the formation and metabolism of fecal carcinogens (Thorton et a[., 1983). Beer might interact with the diet either to influence the fecal flora of the gut, or the steroid concentration in the gut, or alter the gut transit time (Zaridze, 1983; Kabat et al., 1986). Soju, made of
385
distilled barley and potatoes, is the most common alcoholic drink in Korea. Most of the subjects studied drank beer infrequently. This study did not consider beer consumption. However, it is difficult to dismiss the possibility of a relation between ethyl alcohol and colorectal cancer, especially rectal cancer. One could hypothesize that the risk may be associated with the type of alcohol to which humans are exposed. The various components of whiskey, beer, wine and gin may work in conjunction with alcohol to produce cancer. In summary, esophageal cancer was found to be significantly related to smoking and alcohol drinking. None of the other digestive tract cancers was associated with smoking. There was an elevated risk of cancer of the liver and rectum among alcohol consumers. The present findings could have important public health implications. Although the results of epidemiological studies of smoking and alcohol, and cancer of the stomach, liver, colon and rectum especially remain conflicting and inconsistent, in defining policies for prevention, it cannot be overlooked that cigarette smoking and alcohol consumption do appear to be risk factors for digestive tract cancers. It is suggested that a more widely and systematically conducted, comparative casecontrol study could be effective in identifying common, inverse or independent risk factors for the studied cancer. ACKNOWLEDGEMENTS
We thank Dr. Y.H. Lee, Seoul National University, for helpful comments and Mr. H. Won and Mr. K.H. Kim, KCCH, for their help in this work.
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