Hot and cold mate drinking and esophageal cancer in Paraguay. P A Rolón, X Castellsagué, M Benz, et al. Cancer Epidemiol Biomarkers Prev 1995;4:595-605. Published online September 1, 1995.
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I, ‘j
4, 595-
605,
Hot
1995
Sepienher
and
Cancer
Cold
Mate
Pedro Anibal Rol#{243}n,Xavier and Nubia Muiioz’
Drinking
Castellsagu#{233},
Maja
and
Benz,
Lahoratorio de Anatomia Patoldgica y Citologla. Ygatimi 853. Asuncirin, Paraguay IP. A. RI: Servei d’Epidemiologia i Registre del Cancer. Institut Catal#{224}d’Oncologia. Ciutat Sanit#{224}riai Universit#{224}ria de Bellvitge. Autovia (‘astelldefels K. 2.7, E-08907 Hospitalet de Llobregat. Barcelona. Spain
IX. Cl: Thomas,
and
International
F-69372
Lyon
Agency cedex
08,
for
Research
France
IM.
on Cancer.
150.
Cours
Albert
B., N. M.I
Abstract A hospital-based case-control study, including 131 cases of esophageal cancer and 381 controls, was carried out in Paraguay to investigate the role of hot and cold mate drinking in esophageal cancer risk. Detailed information on mate drinking and on tobacco smoking, alcohol consumption, and dietary habits was obtained by interview. Amount and duration of cold or hot mate drinking were not associated with esophageal cancer risk. However, temperature at which mate was drunk was significantly associated with risk. As compared to drinkers of warm or hot mate, drinkers of very hot mate had an increased risk for esophageal cancer even after adjusting for the strong effects of alcohol and tobacco consumption (adjusted odds ratio = 2.4; 95% confidence interval = 1.3-4.3). This effect seemed to be mainly due to the temperature at which mate cocido (one of the two ways in which hot mate is prepared) was drunk (odds ratio = 6.5; 95% confidence interval = 3.2-13.2). As expected, very strong dose-response associations were found for alcohol consumption and cigarette smoking. After correcting for these and the consumption of other food groups, diets rich in fats and red meats, especially beef, were associated with esophageal cancer risk. In conclusion, the findings from this study suggest that cold mate drinking does not increase the risk of esophageal cancer. This study identifies the very hot temperature at which mate is drunk, and not the amount or the duration, as an important risk factor for esophageal cancer in this population. Alcohol drinking and tobacco smoking remain, nevertheless, the main risk factors for esophageal cancer in Paraguay. Introduction
Esophageal
Received 2/9/95; revised 5/12/95; accepted 5/15/95. I To whons requests for reprints should he addressed.
Cancer
Biomarkers
& Prevention
in Paraguay
cancer are one of the highest in America, in particular, in the northeastern region that borders Brazil in which a mortality rate of 40/100,000 has been reported in males (3). Populations in these high risk areas share the habit of drinking large quantities of mate, a local tea prepared as an infusion of the herb flex paraguavensis and that is usually drunk very hot. Because of this, it has long been hypothesized that mate drinking may play an etiological role in the high incidence of esophageal cancer in these areas. To this end, the IARC has coordinated a series of studies in these countries. Results from the studies in Brazil (4), Uruguay (5, 6), and Argentina (7) have yielded inconsistent results. Although there was a dose-response effect of hot mate amount consumed in Uruguay, a nonsignificant increase in risk among daily drinkers of mate was found in Brazil, and a marginal association with mate temperature was detected in Argentina. In the same Brazilian population, however, daily drinkers of hot mate had a prevalence of histologically confirmed esophagitis that was three times higher than that of nondrinkers (8). One of the challenges in studying the association between mate drinking and esophageal cancer is to assess whether its potential effect is related to the herb itself (due to potential carcinogenic compounds), to the high temperature at which it is usually consumed (which may result in chronic esophageal thermal injury), or to a combination of both. In Paraguay we had the opportunity of trying to disentangle these two effects as mate is drunk both hot and cold. Hot mate is drunk in two ways: ( a) as the mate infusion or “regular” mate, as it is prepared as in Brazil, Argentina, and Uruguay and is usually drunk warm, hot, or very hot from a gourd through a metal straw; and (b) “mate cocido, “ which is prepared by boiling the water and the mate herb mixed together passed through a strainer and drunk hot or very hot from a cup or jar. Cold mate or “terer#{233}” is prepared as mate cocido but it is drunk refrigerated from a cup, glass, or jar. Thus, by estimating the effect of hot mate drinking (combined consumption of regular mate and mate e’oe’ido) and cold mate drinking (consumption of terer#{233})the relationship between mate, its consumption temperature, and esophageal cancer risk can be further studied. To explore these associations taking into account other risk factors for esophageal cancer (socioeconomic indicators, tobacco smoking, alcohol consumption, and dietary food items), a hospital-based case-control study was carried out in Paraguay. Subjects
There is a cluster of high incidence areas of esophageal cancer in South America, which includes Northeastern Argentina, Southern Brazil, Uruguay, and Paraguay. Age-standardized incidence rates in this region range from 1 1/100,()00 in Asunci#{243}n, Paraguay and Partido de La Plata, Argentina to 26/100,000 in Porto Alegre, Brazil (1, 2). In Uruguay, mortality rates for this
Epidemiology,
and
Methods
A protocol and questionnaire similar to those previous studies in Brazil, Uruguay, and Argentina adapting some questions to the local situation.
used in the were used.
Cases. Cases were subjects residents in Paraguay, newly diagnosed of esophageal cancer by cytology, histology, or radiology identified in four hospitals and all private clinics, pathology laboratories, and radiology clinics in Asunci#{243}n between January 1988 and March 1991. Patients older than 75 years of age, those who had not been residents in Paraguay for at least S years, and those who were in poor physical condition or too
Downloaded from cebp.aacrjournals.org on July 18, 2011 Copyright © 1995 American Association for Cancer Research
595
596
Male
Drinking
and
Esophageal
Cancer
in Paraguay
ill to obtain reliable information were excluded. Cases had to be interviewed within 3 months after diagnosis. It is estimated that virtually all cases of esophageal cancer looking for medical care should be identified in one of these medical facilities. Controls. For each case enrolled in the study, three controls who were selected from the same hospitals and admitted during the same period as the cases and matched by sex and age (±5 years), were identified and included in the study. The same exclusion criteria used with the cases were applied to the controls. Patients who had diseases thought to be associated with smoking or alcohol were also excluded. The main diagnostic categories among controls were: malignant tumors (not associated with alcohol or tobacco, such as skin cancer, lymphomas, leukemia, and prostate cancer), 36.7%; benign tumors, 16.1%; urinary tract diseases, 16.2%; inguinal and abdominal hernias, 12.7%; colitis and megacolon, 6.6%; skin disorders, 3.9%; rheumatic and congenital heart diseases, 3.5%; varicose veins, 2.6%; and mycosis, 1.6%. Questionnaire. All eligible cases and controls were interviewed at the hospitals according to a pretested standardized questionnaire by six trained interviewers (social workers and medical students). The questionnaire elicited information on socioeconomic-, tobacco smoking-, and alcohol consumptionrelated variables, ?izate, mate cocido, and terer#{233}drinking and included also a double food frequency questionnaire with 50 dietary items for current and past (10 years before) consumption. Statistical Analyses. For all analyses, exsmokers and exdrinkers of alcohol or iilate were defined as those stopping the habit at least 1 year before the date of the interview. Accordingly, those subjects who left the habit within I year before the date of the interview were considered as current smokers or current drinkers. Because there were only three cases and nine controls who were never exposed to any of the three types of mate, quartiles of amount of consumption were computed among cases and controls, and the lowest quartile was used as the reference category. Food items were grouped into 16 food groups as follows: red meats, processed meats, cheese, soja, cereals, cereal products, roots and tubers, vegetables, citrus fruits, noncitrus fruits, fats, oils, poultry, fish, milk, and eggs. For each food group monthly average amounts of consumption were computed and ranked into quartiles. Because of the matched study design, conditional logistic regression was first used to assess the effects of the major risk factors after adjusting for potential confounders. Although the estimates were very similar in magnitude, they were less precisc than those obtained with unconditional regression. Therefore. all analyses presented were performed by means of unconditional regression, including the design variables of the study, sex, age group (four categories), and hospital group (five categories), in all logistic models. The maximum likelihood method was used to estimate model parameters (9). This procedure provides estimates of model parameters which, appropriately transformed, yield the OR2, a measure of association between a given risk factor and the disease and which can be interpreted as an approximation of the relative risk. Regression models for socioeconomic and demographic variables and mate-related variables and food groups were further adjusted by the lifetime number of cigarettes smoked and the lifetime consumption of pure ethanol. To test for the overall effect of a variable, as well as to assess effect modifi-
2
The
abbreviations
used
are:
OR,
odds
ratio:
Cl.
confidence
interval.
cation (i.e. , statistical interaction between two risk factors) likelihood ratio test statistic was used. Test for trends amount or duration were performed by coding the categories successive integers and by using the likelihood ratio test tistic with one degree of freedom. Statistical significance set at the 0.05 level and, accordingly, 95% CI around the are presented.
the with in stawas OR
Results A total of 132 cases and 393 controls were invited to participate. Of these, 1 case refused to participate and 381 (97%) controls agreed to reply to the questionnaire. The distribution of the main characteristics of cases and controls is presented in Table 1 for males and females. There were no marked differences in socioeconomic status between cases and controls in the male population. Among females, cases were more likely than controls to come from rural areas and to have received less education. Both male and female cases were more likely than controls to be mestizos, drinkers of alcohol and smokers. This is not surprising because control patients with smokingor alcohol-related diagnoses were not enrolled in the study. The most common type of alcohol beverage consumed in this population was aguardiente distilled from sugar cane (Table 1). Mate. Hot mate drinking was virtually ubiquitous in this population. Over 95% of cases and controls were or had been drinkers of hot mate. The prevalence of ever-terer#{233} drinking was 83% in male cases, 83% in male controls, 62% in female cases, and 47% in female controls (Table 1). There were only 1 case and 2 controls who were terer#{233}drinkers and who were nonhot mate drinkers. The mean daily amounts of regular mate, mate cocido, and terer#{233}drunk were 0.75, 0.25, and 1.35 liters, respectively, among controls and 0.92, 0.27 and 1.79 liters, respectively, among cases. As shown in Table 2, amount and duration of hot mate drinking and terer#{233}drinking were not positively associated with esophageal cancer risk after adjusting for the combined effects of tobacco smoking and alcohol consumption. This was also true for regular mate and mate cocido (data not shown). It is worth noting that most of the estimates associated to each quartile of mate consumption, although not significant, were below one suggesting a small protective effect. Moreover, we found an unexpected statistically significant inverse trend with duration of hot mate drinking. The main finding for the mate-related variables was that the self-reported temperature at which hot mate was drunk was positively and significantly associated with esophageal cancer risk with an OR of 2.4 (95% CI = 1.3-4.3) for very hot mate drinking. When the relationship was explored further it was found that the effect was mainly due to the temperature at which mate cocido, but not regular mate, was consumed. Thus, compared to warm/hot drinkers, very hot drinkers of mate cocido had an OR of 6.5 (95% CI 3.2-13.2). In contrast, the corresponding OR for regular mate was 1.7 (95% CI = 0.93. 1). The effect of hot mate temperature persisted after adjusting for hot mate amount (OR = 2.6; 95% CI = 1.4-4.8), for total mate amount (OR = 2.4; 95% CI = 1.3-4.4), or for duration of hot mate drinking (OR = 2.3; 95% CI = 1.3-4.2). This was also true for mate cocido for which the increased risk associated to temperature was even larger after adjusting for the amount of hot mate consumed (OR = 7.1; 95% Cl = 3.3-15.0), for total mate amount (OR 7.1; 95% CI = 3.3-15.0), or for years of hot mate drinking (OR = 6.9; 95% CI = 3.2-14.9). Having found an independent temperature effect, we further
Downloaded from cebp.aacrjournals.org on July 18, 2011 Copyright © 1995 American Association for Cancer Research
Cancer
Table
I
Distributio
n of mai n char acterist
ics of cases
and
control
EpidemioIo,
Total
Controls (%)
110
Age
Females
Cases a
& Prevention
s by sex
Males Variables
Biomarkers
n
Cases (%)
318
n
Controls (%)
21
n
(%)
63
group (5.5)
21
(6.6)
2
(9.5)
4
(6.4)
4(3-55
21
6
(19.2)
53
(16.7)
4
(19.0)
11
(17.5)
56-65
41
(37.3)
119
(37.4)
5
(23.8)
23
(36.5)
42
(38.2)
125
(39.3)
10
(47.6)
25
(39.7)
39
(35.4)
109
(34.3)
6
(28.6)
21
(33.3)
37
(33.6)
138
(43.4)
7
(33.3)
33
(52.4)
(2.8)
2
(9.5)
3
(4.8)
(18.5)
4
(19.0)
6
(9.5)
(0.9)
2
(9.5)
0
4;45
Hospital University Cancer
hospital hospital
Military
hospital
Social
Security
Other Main
8 21
sources
5
9
(7.3) (19.1)
59
(4.5)
3
residence
Urban
55
(50.0)
145
(45.6)
11
(52.4)
38
(641.3)
Rural
54
(49.1)
173
(54.4)
1(1
(47.6)
25
(39.7)
1
Unknown Ever
(0.9)
0
t)
0
schooling
Ever
89
(80.9)
226
(71.1)
9
(42.9)
37
(58.7)
Never
2()
(18.2)
86
(27.0)
12
(57.1)
25
(39.7)
Unknown
I
(0.9)
6
(1.9)
1
0
(1.6)
Race White
65
(59.1)
221
(69.5)
12
Mestiza
44
(40.0)
97
(30.5)
9
Other Smoking
(0.9)
6
(5.4)
0
47
(74.6)
(42.9)
16
(25.4)
0
0
status 136
(42.8)
12
(57.1)
48
Past
32
(29.1)
76
(23.9)
3
(14.3)
4
(6.3)
Current
72
(65.4)
106
(33.3)
6
(28.6)
11
(17.5)
(4.5)
146
(45.9)
11
(52.4)
56
(88.9)
Never
Ethanol
5
Past
32
(29.1)
Current
73
(66.4)
Ever spirits (aquardienk’)
94
(85.5)
Ever wine
28
(25.5)
38
Ever beer
25
(22.7)
56
Type
(76.2)
status
Never
of alcoholic
(13.5)
3
(14.3)
2
(3.2)
129
(40.6)
7
(33.3)
5
(7.9)
102
(32.1)
7
(33.3)
1
(1.6)
(11.9)
4
(19.0)
6
(9.5)
(17.6)
2
(9.5)
0
7
(2.2)
0
43
drink
Ever other Hot
1
(57.1)
0
3
(2.7)
Never
4
(3.6)
10
(3.1)
0
(1.6)
Past
9
(8.2)
10
(3.1)
0
(3.2)
status
mate
(male
and
Current Mean
daily
male
c-oc-ido
combined)
97 amount
(liters)
(88.2)
298
1.03
(93.7)
0.88
21
(1(10.0)
60
(95.2)
0.86
1.29
Terer#{233}status Never
19
(17.3)
53
(16.7)
8
Past
15
(13.6)
26
(8.2)
0
Current
76
(69.1)
239
(75.2)
13
Mean
daily
amount
(liters)
1.92
explored whether the amount of hot mate was important among those drinkers who had the habit of having it very hot. Thus, when restricting the analysis to very hot mate drinkers (90 cases and 220 controls), the amount of hot mate was not associated with an increased risk. Other explored mate-related variables not associated with esophageal cancer included, for each type of mate: the addition of herb, the addition of sugar, the type of water used (well, tank, or running water), and the time elapsed since stopping the habit, which was barely possible to assess because of the small
I .42
(38.1)
33
(61.9)
25
(52.4) (7.9)
0.88
(39.7)
0.7))
number of subjects quitting mate drinking (data not shown). No significant interactions were found between any of the measurements of mate drinking and cigarette smoking or alcohol consumption, although the statistical power to significantly detect such effect modifiers was limited. Smoking. Table 3 summarizes the main findings for smoking-related variables. As expected, all measurements of tobacco smoking were independently and strongly associated with esophageal cancer risk with a clear dose-response re-
Downloaded from cebp.aacrjournals.org on July 18, 2011 Copyright © 1995 American Association for Cancer Research
597
598
Mate
Drinking
and
Esophageal
Cancer
in Paraguay
Table
2
Effect
of selected
variables
mae-reIated
on esophageal
Cases
OR1”
Variables
(%)
a Hot
male
status
and
(male
cancer
male
cocido
risk
Controls (95%
CI)
OR,”
(95%
Cl)
(%)
n
combined)
Never
4
(3.1)
11
(2.9)
1.0
Past
9
(6.9)
12
(3.1)
2.4
(0.6-10.6)
1.0 1.0
(0.1-7.5)
(0.3-3.4)
0.5
(t). 1-2.2)
1 18
(90.1)
358
(94.0)
1.0
Never
27
(20.6)
86
(22.6)
1.0
Past
15
(11.4)
31
(8.1)
1.3
(0.6-2.9)
1.0
(0.3-2.8)
Current
89
(67.9)
264
(69.3)
1.0
(0.6-1.6)
0.9
(0.5-1.8)
Current Terer#{233}status
Hot
mate
amount and ,nale
(mate
(liters/day cocido
1.0
quartiles) combined) 38
(29.0)
90
(23.6)
I .0
Low
(0.51-0.79)
17
(13.0)
93
(24.4)
0.4
(0.2-0.8)
0.4
(0.2-0.8)
High
(0.80-1.10)
37
(28.2)
1 16
(30.4)
0.8
(0.5-1.4)
0.8
(0.4-1.5)
(>1.10)
39
(29.8)
82
(21.5)
1.2
(0.7-2.0)
0.9
Lowest
(0-OS)
Highest
1.0
Terer#{233}amount
(liters/day
quartiles) 35
(26.7)
96
(25.2)
I .0
Low
(0.17-0.80)
32
(24.4)
104
(27.3)
0.7
(0.4-1.3)
0.8
(0.4-1.7)
High
(0.81-1.6)))
24
(18.3)
100
(26.2)
0.6
(0.3-1.2)
0.6
(0.3-1.3)
(>1.60)
40
(30.5)
78
(20.5)
I .3
(0.7-2.3)
1.0
(0.4-2.1)
Lowest
(0-4). 16)
Highest
3
Unknown
I .0
(0.8) 0.75
P for trend Hot
duration combined)
male
cocido
(yrs)
and
(male
male 4
(3.1)
11
(2.9)
I .0
1-29
19
(14.5)
37
(9.7)
I .8
(0.5-6.6)
1.2
(0.2-6.4)
30-39
22
(16.8)
73
(19.2)
0.9
(0.3-3.3)
0.4
(0.1-2.0)
40-49
43
(32.8)
100
(26.2)
1.2
(0.4-4.2)
0.6
(0.1-2.8)
S0
43
(32.8)
160
(42.0)
0.7
(0.2-2.5)
0.3
Nondrinker
P for trend
(drinkers
Terer#{233}duration
(yrs) 27
(20.6)
86
(22.6)
I .0
1-29
17
(13.0)
51
(13.4)
0.9
(0.4-2.0)
0.9
(0.3-2.3)
30-39
33
(25.2)
73
(19.2)
I .4
(0.7-2.6)
1.2
(0.5-2.8)
40-49
38
(29.0)
103
(27.0)
1.1
(0.6-2.0)
1.0
(0.5-2.3)
50
16
(12.2)
66
(17.3)
0.6
(0.3-1.4)
0.6
(0.3-1.6)
Hot male cocido
2 (drinkers temperature combined)
Warm,
(male
hot
mare
37
(28.2)
150
(39.4)
I .0
90
(68.7)
220
(57.7)
2.2
4
cocido
(0.5) 0.92
and
Nondrinker Male
I .0
only)
Very hot
(3.1)
11
I.0 (1.4-3.5)
2.4
(1.3-4.3)
(2.9)
temperature 61
(46.6)
269
(70.6)
1.0
hot
40
(30.5)
29
(7.6)
6.6
(3.7-11.7)
6.5
(3.2-13.2)
Nondrinker
30
(22.9)
82
(21.5)
1.7
(1.0-2.8)
1.9
(1.0-3.6)
Warm, Very
hot
Unknown OR1.
(0.1-1.3) 0.01
Nondrinker
P for trend
h OR,
I .0
only)
Unknown
“
(0.4-1.7) 0.95
P for trend
adjusted adjusted
2 for design for design
variables variables,
age group, sex, and hospital lifetime cigarette consumption,
group. and lifetime
lationship. Stopping cigarette smoking had a beneficial effect on risk, although a 2-fold increased risk persisted after quitting for more than 20 years. As shown in Table 3, there was a modest marginal effect of type of tobacco; as compared to black tobacco smoking, blond tobacco smoking was associated with a 50% reduction in risk. After allowing for the number of cigarettes smoked and the amount of ethanol consumed, the reduced risk associated with blond tobacco persisted, although it was not statistically significant. Other explored smoking-related variables that showed a statisti-
alcohol
I.0
(0.5) consumption.
cally significant effect were rolled cigarette smoking and average numbers of black cigarettes smoked/day. In contrast, no associations were found with tobacco chewing, use of filter in cigarettes, intensity of smoke swallowing, or average amount of blond cigarettes smoked/day (data not shown). When average daily amount and duration of cigarette smoking were adjusted for each other, both variables remained statistically significant (P values for the likelihood ratio statistic:
