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[CANCER RESEARCH 50, 426-431, January 15, 1990]
Mate Drinking, Alcohol, Tobacco, Diet, and Esophageal Cancer in Uruguay
Eduardo De Stefani, Nubia Muñoz,1Jacques Estève,Alberto Vasallo, Cesar G. Victora, and Sibylle Teuchmann
Department of Epidemiology, Oncology Institute, Avenida Brasil 308 dep 402, Montevideo, Uruguay [E. D. SJ; International Agency for Research on Cancer, ISO, Cours
Albert Thomas, F-69372 Lyon cedex 08, France [N. A/., /. £., S. T.J; National Cancer Registry, Eduardo Acevedo No 1530, Montevideo, Uruguay [A. Y.J; and
Departamento de Medicina Social, Faculdade de Medicina, Universidade Federal de Pelotas, Caixa Postale 464, 96100 Pelotas, RS Brazil [C. G. V.J
ABSTRACT
A case-control study was conducted in Uruguay to investigate the role
of mate drinking, alcohol, tobacco, and certain dietary factors in the
etiology of esophageal cancer. The study included 261 patients with
squamous cell carcinoma of the esophagus and 522 hospital controls
matched by sex and age. A strong association with a clear dose-response
relationship was observed with the amount of mate drunk daily and
duration of the habit. The relative risk for those drinking over 2.5 liters
of mate per day was 12.2 (95% confidence interval, 3.8-39.6) after
adjusting for the effects of age, area of residence, alcohol, and tobacco.
Strong associations were also observed with tobacco smoking and alcohol
drinking which appear to act in a multiplicative way. The relative risk
for those who smoke and drink heavily compared to that of light smokers
and drinkers was 22.6. The risk associated with black tobacco was about
three times higher than that associated with blond tobacco. A clear
protective effect was found for the consumption of fruits and vegetables
but a dose-response relationship was present only for fruits. Finally, an
increased risk was also found for those eating barbecued meat daily.
INTRODUCTION
Esophageal cancer is characterized by worldwide geographi
cal variation in incidence and mortality rates, even within small
areas (1). In South America, the highest rates have been re
ported in Uruguay, a small country which shows large variation
in the rates of esophageal cancer. The mortality rates for males
range from 40 per IO5 in the northeast region, which borders
Brazil, to 10 per 10s in the capital city of Montevideo (2). The
High risk areas in South America (southern region of Brazil,
Uruguay, and Argentina) offer a unique opportunity to study
this problem. This is due to the fact that their populations share
the habit of drinking large quantities of a local tea, known by
the folk name of mate. This beverage, an infusion of the herb
Ilex paraguayensis, is drunk very hot through a metal straw.
Despite the fact that the prevalence rate of exposure is over
80%, there remains a well-defined nonexposed group. A pre
vious case-control study in Uruguay, in which routinely col
lected information on mate drinking was extracted from the
clinical records of patients with esophageal cancer and other
cancers, showed a strong association with mate drinking (RR
= 4.7, 95% CI = 1.9-12.1), after adjusting for the effects of age
and alcohol and tobacco consumption (2).
Although a subsequent case-control study in southern Brazil
did not show a strong association between mate drinking and
esophageal cancer, the moderate increase in risk and the high
prevalence of mate drinking in this population could account
for a considerable proportion of esophageal cancers occurring
(4).
This case-control study was designed to obtain further infor
mation on the hypothesis that mate ingestion is associated with
the risk of developing esophageal cancer.
SUBJECTS
death rates are lower for females, with a male/female ratio of
3.8 for the whole country.
Cancer of the esophagus can be divided into those cancers
essentially due to alcohol and tobacco and those in which these
two factors do not appear to play an important part. The joint
effect of tobacco and alcohol exposures accounts for about 80%
of the etiology of the disease in North America (3), South
America (2, 4), Europe (5), South Africa (6), and some Asian
countries (7).
On the other hand, in areas with extremely high incidence
such as Iran and China, alcohol and tobacco appear to play a
minor role (8, 9) and the main risk factors remain to be
identified. There is evidence suggesting that opium tar may be
the major cause in Iran (10), and yV-nitroso compounds have
been proposed as possible etiological candidates but convincing
evidence is still lacking in China (11).
Factors producing chronic injury to the esophagus, such as
rough foods, hot beverages, and certain vitamin deficiencies,
may increase susceptibility to carcinogens.
Esophageal thermal injury resulting from drinking hot bev
erages is a very difficult issue to study epidemiologically because
of the widespread consumption of these drinks and the unreli
ability of data on temperature obtained through interviews.
Received 6/14/89; revised 9/29/89; accepted 10/16/89.
The costs of publication of this article were defrayed in part by the payment
of page charges. This article must therefore be hereby marked advertisement in
accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1To whom requests for reprints should be addressed, at International Agency
for Research on Cancer, 150 Cours Albert-Thomas, 69372 Lyon, Cedex 08,
France.
AND METHODS
The basic protocol utilized in the Brazilian study (4) was used in this
study. The Brazilian questionnaire was adapted to the local situation
of Uruguay, especially in relation to type of tobacco and diet.
In the study period from July 1985 to September 1988, 283 cases
with clinical and/or radiological diagnosis of esophageal cancer were
admitted to the four main hospitals in Montevideo. These centers have
a catchment area which covers 45% of the population of Montevideo
and about 55% of the rest of the country. Patients treated in these
hospitals are covered by Social Security medical care and have rather
low incomes. Conditions for eligibility were: (a) to have histológica!
diagnosis of squamous cell carcinoma; (b) to have been diagnosed
within the previous 4 months; (c) to have lived in the country for at
least 5 years; (</) to be in sufficiently good physical and mental health
to give reliable answers to the questionnaire. Proxy interviews were not
accepted. Cases were ascertained shortly after clinical diagnosis through
the hospital cancer registries operating in the participating centers.
None of the patients refused to be interviewed and 15 patients were
excluded, 12 because no histológica! confirmation was available and
three because of a diagnosis of adenocarcinoma. Of the remaining 268
patients, seven could not be interviewed due to terminal illness. The
remaining 261 patients were included in the study. For each case, two
controls matched by age (±5years) and sex were interviewed. Condi
tions for eligibility were: (a) to be admitted to the same hospitals; (¿>)
not to have a diagnosis of tobacco and/or alcohol-related diseases; (c)
to have lived in the country for at least 5 years. The main diagnostic
categories among the controls are listed in Table 1.
The questionnaires were completed by four trained social workers.
Information was collected on socioeconomic status (education, income,
and occupation); on the lifetime habits of drinking mate, coffee, and
tea (quantity, duration, and temperature); alcohol drinking (dose, ex
pressed in milliliters of alcohol, duration, and type of alcoholic bever
age); and tobacco smoking (type of tobacco, duration, intensity, and
cessation periods). Dietary habits were assessed in two time periods:
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ESOPHAGEAL CANCER [N URUGUAY
Table 2 Distribution afeases and controls according to main risk factors
Table 1 Diagnostic categories among control patients
ICD-9550-553360-379574-575153-154600540-542174172-173454185200-208186-187730-731|690-698122240-541581-594210-229281-289DiagnosisInguinal
MaleNumberAge<5455-6465-7475+ResidenceMontevideoNorthSouthUrbanRuralYears
herniasDiseases
and abdominal
eyeGallbladder
of the
disordersColorectal
cancerProstatic
hypertrophyAppendicitisBreast
cancerSkin
cancerVaricose
veinsProstatic
cancerLymphoma-leukemiaCancer
tumorsOsteomuscular
of the testis and other genital
diseasesOther
tumorsSkin
malignant
disordersHydatid
cystDisorders
study0-23-45-67+Income
of
glandUrinary
of the thyroid
diseasesBenign
tract
tumorsBlood
disordersNo.76735846363328262424161313121288754522%14.614.011.18.86.96.35.45.04.64.63.12.52.52.32.31.51.51.31.00.7100.0
" 142, 156. 171, 193.
pesos)<5.9996,000-11,99912,000-23,99924,000-47.999248,000Smoking
(in
the period just before the onset of symptoms and 10 years before
admsission to the hospital. A food frequency questionnaire was used to
assess the consumption of the various food items. The same 10 food
groups used in the Brazilian questionnaire were included, i.e., fresh
meat, processed meat, barbecued meat, eggs, cereals, potatoes and sweet
potatoes, vegetables, fresh fruits, fats, and dairy products.
The statistical analysis was done by linear logistic modelling (12)
using the unconditional method with the GLIM software (13). An
unconditional analysis was done because it is generally accepted that in
a matched study, this analysis can be performed if appropriate adjust
ment is made for the matching variables that in this study were sex,
age, and hospital. Moreover, the results obtained with the conditional
analysis were practically identical to those obtained with the uncondi
tional one. Relative risk estimates were approximated by odds ratios
and were calculated after adjustment either for age and residence or for
age, sex, and residence when a common relative risk for male and
female was estimated. Adjustment for residence was made because it is
known that the rates for esophageal cancer are higher in rural than
urban areas in Uruguay. Trend tests were performed by adjusting a
linear model using the numbers of the categories as covariate and
adjusting simultaneously for all relevant categorized cofactors. The
control group was subdivided into controls with other cancers and
controls without cancer. The statistical analysis for the main risk factors
yielded similar results for both subgroups and in addition the \ ' tests
statusNonsmokerSmokerExsmokerType
tobaccoBlackBlondMixedDrinking
of
habitNondrinkerCurrent
drinkerOccasional
drinkerExdrinkerType
alcoholWine
of
drinkerSpirit
drinkerBeer
drinkerMate
18.168.523.4
statusNondrinkerCurrent
drinkerExdrinkerCase19911.6-31.137.719.620.127.152.854.845.234.730.728.16.518.624.627.120
" This value and subsequent values in this column represent percentages.
for heterogeneity were nonsignificant. Thus both subgroups were com
bined in the final analysis.
tion. The risk increases significantly after an average consump
tion of 50 ml of pure alcohol per day in males and earlier in
females. Among the latter, however, the estimates are unstable
due to the small number of drinkers. The trend tests for testing
the effect of alcohol and tobacco are nevertheless highly signif
icant (x2 with one degree of freedom are respectively, 4.9 and
5.5), and the interaction between tobacco, alcohol, and sex was
not significant but the CIs were very wide. As only two female
cases and one control smoke more than seven cigarettes and
drink more than 50 ml of alcohol a day, the combined effect of
alcohol and tobacco could be evaluated only in males. In Table
4 the number of nonsmokers and nondrinkers were put together
with those of light smokers and drinkers because the number
of the former was too small (one case and 32 controls). Table
4 shows that a multiplicative model gives a good description of
the data, but no formal test of this model could be done with
the limited number of cases available. The joint effect of dura
tion of tobacco smoking and alcohol consumption yielded sim
ilar results with a less good Tit.
The risk for esophageal cancer decreased significantly among
RESULTS
A total of 261 cases (199 males, 62 females) and 522 controls
were included in the study. Their distribution by age, sex,
residence, education (years of schooling), income, and some
risk factors is given in Table 2. Cases, especially males, are
more often rural and have lower socioeconomic status than
controls. The association of these variables with esophageal
cancer was evaluated as follows.
Effects of Alcohol and Cigarette Consumption. Tobacco smok
ers and alcohol drinkers were defined as those who smoked or
drank alcoholic beverages, for at least 1 year, independently of
the amount. Cases and controls were classified according to the
lifetime consumption of cigarettes and alcoholic beverages,
duration and daily consumption.
The distribution of alcohol and cigarette consumption being
very different in males and females, the evaluation of these risk
factors has been done separately for each sex. Table 3 shows
the relative risks and their CIs2 for various levels of consump2 The abbreviations used are: CI, confidence interval; RR, relative risk.
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ESOPHAGEAL CANCER IN URUGUAY
Table 3 Relative risk for cigarette and alcohol consumption
adjusted for each other and for age and residence (confidence
interval in parentheses)
MalesCigarettes
cases7142862
controls565475101 RR11.93(0.7-5.4)2.66(1.1-6.8)4.26(1.7-10.4)
cases4111•381212FemalesNo.
controls105118882412Adjusted
RR]2.27
day)01-78-1415-24
(per
(0.9-6.0)3.22(1.11-9.3)1.04(0.4-2.4)1.89(
25+Alcohol
4.62(1.9-11.1)10.85(0.4-1.8)0.71
88261612504649No.11210061511173831Adjusted
day)01-2425-4950-149150-249250+No.
(ml per
(0.3-1.6)1.37(0.8-2.4)3.57(1.9-6.7)5.27(2.7-10.2)No.
Table 4 Age and residence-adjusted relative risks for the joint effect of alcohol
and tobacco consumption
number of cigarettes per day (data not shown).
As shown in Table 2, most of the male smokers in Uruguay
day0-71(7)2.7(7)3.9(3)10.4(1)22.7(3)1(21)8-143.0(12)2.4(5)8.2(4)16.1(2)18.1(5)1.8(28)15-243.3(16)6.1(17)21.4(17)13.5(7)22.5(5)2.9(62)25+4.5(19)6.5(21)15.1(
per
smoked
either black or blond tobacco. Black tobacco was used
Alcohol
(RR for
by 69% of male smoker cases against 47% among controls. In
day)0-4950-149150-249250-349350+Total
(ml per
alcohol)1(54)1.6(50)4.1(46)5.1(16)6.7(33)(199)
addition, 64% of cases and 40% of controls smoked black
tobacco only. This difference was highly significant after con
trolling for daily dose of alcohol and tobacco. The risk for those
who have smoked mainly black tobacco compared to that of
those who smoked mainly blond tobacco was 2.6 (95% CI, 1.73.9). For mixed smokers, mainly black tobacco smokers were
those who have smoked more black tobacco than blond tobacco
over their life-span. Moreover, the effect of type of tobacco
(RR for cigarette)Cigarettes
combines multiplicatively with duration of smoking (Table 5).
Among male smoker patients, 19% used filter cigarettes
against
28% among controls. This apparent protective effect of
male exdrinkers (P = 0.01) and there was a significant trend
filters was however no longer significant after adjustment for
with years since quitting: the RR values adjusted for age, alcohol, cigarette consumption, and type of tobacco: the use of
residence, and amount of cigarettes per day, with the regular
filter cigarettes was in fact similar in cases and controls after
drinkers as reference category, were as follows: 1-9 years since
stratification by type of tobacco.
quitting 0.78 (95% CI, 0.48-1.26), >10 years 0.46 (0.23-0.92),
No cases or controls used pipes or cigars.
nondrinkers and occasional drinkers 0.48 (0.29-0.81) (P =
Dietary Factors. In the following analyses, all risk evaluations
0.001).
were made after adjustment for age, sex, region, alcohol, dura
Influence of the Type of Alcoholic Beverage. The distribution
tion of cigarette smoking, and type of tobacco smoked. The
of type of alcohol consumed by the study subjects changes with current and past frequencies of consumption of the 10 food
their total consumption of alcohol; as a consequence, this groups were compared between cases and controls and no
distribution differs between cases and controls. Light drinkers
significant differences were found. Therefore the current con
tend to drink more beer and wine and less spirits than heavy sumption was used in the analysis. The 10 food groups were
drinkers. On the other hand, heavy drinkers tend to drink more
fresh meat, preserved meat, barbecued meat, fat, dairy products,
spirits than light drinkers. Since total alcohol consumption is eggs, cereals, potatoes, vegetables, and fresh fruits. Table 6
given by the sum of the three types of alcoholic beverages, the reports the results for those food groups which have been
average linear increase for each of them separately was calcu
suspected of influencing the risk of esophageal cancer. A clear
lated adjusting for the others and considering each beverage as protective effect and a significant dose-response relationship
a continuous variable. There was a significant difference of was found with the consumption of fresh fruits. A reduction in
effect between beverages. Beer did not contribute to the risk, risk was also observed with the consumption of vegetables but
whereas wine and hard liquor increased the risk by the same without significant dose response. A significant increase in risk
amount for each milliliter of pure alcohol added. Therefore, in
Table 5 Age, residence, and alcohol adjusted relative risks (95% Cl)°for
this population, the sum of liquor and wine consumption is a
duration of smoking and type of tobacco (males only)
better indicator of the risk associated with alcohol consumption
tobaccoMainly
of
(years)
than total alcohol.
adjusted for
Duration of
cigarette smoking
type of
Influence of Other Smoking Variables (Male Smokers Only).
tobacco*1
blond1
black3.2
(years)1-2425-44
When adding to the multiplicative model including age, resi
dence, and average cigarette and alcohol consumption, age at
2.5(1.1-5.7)
2.5
8.1
3.3(1.5-7.3)
start (four categories), number of years since quitting (five 45+Type
4.4Mainly 9.0Duration
1
2.6(1.7-3.9)
categories), and duration (five categories), no effect of age at Type of tobacco adjusted
for duration
start was found, but years since quitting smoking and duration
" The estimation was carried out within the set of male smoker cases and
were found to modify significantly the risk. The assessment of controls.
"The x1 for interaction between the two factors is 1.15 with 2 df.
tobacco exposure by duration gives a better fit than the average
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ESOPHAGEAL CANCER IN URUGUAY
Table 6 Adjusted relative risks for the current consumption of certain food stuffs
DISCUSSION
limes/
once
times/
Food0Fresh
a week111111-3
week0.30(0.1-0.8)1.03(0.7-1.6)0.49(0.3-0.7)0.86(0.6-1.2)0.60(0.4-0.9)>3
week0.38(0.2-1.0)2.07(1.2-3.5)0.48(0.3-0.8)1.04(0.6-1.9)0.48(0.3-0.8)Daily0.61(0.2-1.5)1.44(1.0-2.2)0.56(0.3-1.0)2.66(1.3-5.5)0.33(0.2-0.5)Tren
It is estimated that about 40% of all esophageal cancer cases
occurring in Uruguay during the study period were included in
our study. However, the degree of representativeness of the
study cases cannot be evaluated. With this limitation in mind
we can say that our results indicate that 90% of the cases of
esophageal cancer occurred over the age of 55 and that cases
meatFruits<
tended to live in rural areas and to have a lower socioeconomic
status than the controls, which is in agreement with observa
tions in other populations (4, 6). With regard to etiology, this
" Adjusted for age, residence, smoking duration, type of tobacco, and alcohol
study revealed that, as in similar studies carried out earlier in
consumption.
Uruguay (2) and in Brazil (4), alcohol and tobacco are the main
risk
factors for this cancer and that these two factors appear to
Table 7 Adjusted relative risks for mate drinking0
act in a multiplicative way. The relative risk for those who both
of
of
RR
drink and smoke heavily (over 250 ml of alcohol/day and over
controls48443179518623410423092Adjusted
cases51113378347115810184Number
Cl)12.52(0.8-8.4)3.60(1.3-9.9)6.07(2.1-17.3)12.21(3.8-39.6)13.67(1.1-11.8)4.44(1.7-11.4)2.65(1.1-6.5)6.40(2.5-16.4)
(95%
25 cigarettes/day) was about 20, which was less than that
Daily
liters/day00.01-0.490.50-1.491.50-2.492.50+Duration
amount
reported from France (5). As regards tobacco, this population
offers a special opportunity to compare the effects of the two
types of tobacco, as approximately half smoke blond, flue-cured
tobacco and the other half smoke black, air-cured tobacco. The
risk for smokers of black tobacco cigarettes was increased
almost threefold compared to that of smokers of blond tobacco
cigarettes and it increased even more with duration than with
the number of cigarettes smoked. These findings are in agree
(years)0-1415-2930-4445-5960+Number
ment with results from case-control studies on bladder cancer
in Italy (14), Argentina (15), on laryngeal cancer in southern
Europe (16) and previous studies on cancers of larynx and
oropharynx in Uruguay (17, 18), suggesting that black tobacco
is more carcinogenic than blond tobacco. Moreover, these ob
servations are reinforced by laboratory results showing that the
smoke of black tobacco cigarettes contained more aromatic
" Adjusted for sex, age, residence, alcohol, smoking duration, and type of
amines and tobacco-specific nitrosamines than that from blond
tobacco.
tobacco cigarettes (19) and that the urine of smokers of black
tobacco contained about twice as much mutagenic activity as
for those who eat barbecued meat daily was observed but did the urine of blond cigarette smokers (20).
In relation to alcohol, the risk increases more with the
without a significant dose-response relationship. However, the
amount of alcohol consumed than with the number of cigarettes
increase in risk for those who eat barbecued meat daily persisted
after adjusting for meat consumption. No clear effect for fresh smoked, which is in agreement with the observations made in
meat and fat and no significant associations with the other food the high risk areas for esophageal cancer in France (5). As in
the French studies, the correlation is essentially with the
groups were observed.
amount of alcohol consumed and not with the type of alcoholic
Mate Drinking. Mate drinking is very common in Uruguay.
beverage. In Uruguay, the magnitude of the increase in risk
Only 9% of controls and 2% of cases were nondrinkers. There
associated with the consumption of spirits in males was similar
was a clear dose-effect relationship between amount of mate
drunk each day and the risk of esophageal cancer (Table 7). to that associated with wine drinking, which is not surprising
There was also a less convincing but significant relation with considering that about 80% of the male drinkers are wine
duration of use. The slope of the dose-effect relationship was drinkers and 60% are drinkers of spirits. However, no increased
risk associated with the consumption of beer could be detected
the same for both sexes in each alcohol consumption category
because there are very few beer drinkers among the male drink
and in all smoking categories. There was, however, a significant
absence of effect among blond tobacco smokers (x2 = 8.3 on 2 ers (20%). In contrast with the epidemiological studies which
show that alcohol clearly increases the risk for esophageal
df). There was no significant interaction with any other available
factor. The slope of the dose-effect plot was larger among the cancer even among nonsmokers (21), the laboratory studies
have yielded negative results (22). It has long been suggested
rural population, but not significantly so.
that alcohol may act as a solvent facilitating the transport of
Interaction terms for tobacco smoking, alcohol and mate
carcinogens through the esophageal mucosa (23), but it may
drinking, and socioeconomic status were calculated and found
also act as a chronic irritant, raising the susceptibility to carcin
nonsignificant as expected from the size of the study.
ogens by accelerating cell turnover and thus favoring contact
Influence of Temperature of Hot Beverages. The reported
between the carcinogens and the dividing target cells (1).
temperature of beverages other than mate was not associated
Concerning dietary factors, a clear protective effect and a
with the risk of esophageal cancer. The temperature of mate
had a nonconsistent significant effect: the slope of the dose- dose-response relationship was observed for the consumption
effect relationship was lower among people who reported hot of fruits, which is in agreement with observations made in other
populations (3, 4, 8, 24, 25). Although a protective effect of
mate drinking, and higher and identical among those who report
vegetables was also detected, no dose-response relationship was
warm or very hot. The effect of dose of mate was nevertheless
significant in the three categories of drinkers.
observed. Unfortunately, no distinction was made between raw
meatFatVegetablesBarbecued
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ESOPHAGEAL CANCER IN URUGUAY
and cooked vegetables. No clear effect of fresh meat was found.
A protective effect was found in France (26), but an increased
risk has been associated with fresh meat in Brazil (4). A clear
increase in risk was observed for those eating barbecued food
daily compared to those eating them less frequently, even after
adjusting for meat consumption. This observation is contrary
to the findings of a similar case-control study carried out in a
neighboring area (4), but it is consistent with laboratory inves
tigations showing the presence of animal carcinogens and mutagens in barbecued foods formed by the pyrolysis of proteins
(27).
The present study was designed to study further the associa
tion with mate drinking. A strong association with a clear doseresponse relationship was observed with the amount of mate
drunk daily. The RR for those drinking over 2.5 liters per day
was 12.2 (95% CI, 3.8-39.6), after adjusting for age, tobacco,
and alcohol. A less strong and less clear dose-response relation
ship was observed with duration of the habit. The fact that the
mate effect was present among nonsmokers and light smokers,
and among smokers of black tobacco but not smokers of blond
tobacco, is puzzling. The possibility that blond tobacco smokers
were from a higher socioeconomic level and had a higher intake
of fruit and vegetables was considered, especially in view of a
greater effect of mate drinking among the rural population, but
it was not confirmed. The finding of a significant but not
consistent effect of the temperature at which mate is drunk is
not surprising considering the subjectivity in the perception of
temperature. To evaluate the degree of misclassification in the
reported temperature at which mate is drunk, a validation study
is being carried out in Southern Brazil and in Montevideo.
There are two possible mechanisms through which mate
drinking could increase the risk of esophageal cancer. First, the
plant extract may contain carcinogenic or promoting sub
stances. This possibility was raised in a previous study carried
out in Uruguay (2), but laboratory studies have so far not
demonstrated any promoting or mutagenic activity.3
Secondly, hot mate drinking may increase the susceptibility
of the esophagus to carcinogens. Several epidemiological stud
ies point towards a possible effect of hot drinks on esophageal
cancer incidence. Ecological studies from Japan (28), the Soviet
Union (29), and northern Iran (30) have suggested that inhab
itants of high risk areas drink larger quantities of hot tea than
those of low risk areas. Also in Iran, Singapore, and Puerto
Rico case-control studies indicated similar differences (8, 31,
32). A prospective study carried out in Japan (25) also showed
a higher risk among those drinking hot green tea.
A possible effect of mate drinking on precancerous lesions of
the esophagus has been demonstrated in an endoscopie survey
carried out in Rio Grande do Sul (33). In addition, in a recent
study on chronic esophagitis among young subjects in a high
risk population for esophageal cancer in China, the strongest
risk factor found for esophagitis was the consumption of bev
erages at burning hot temperatures.4
Experimental animal data suggest that hot drinks may poten
tiate the effect of esophageal carcinogens (34). The above ob
servations, and in particular the finding that mate drinking
increases the risks of esophagitis, suggest that mate itself may
not contain specific carcinogens but that its effect may be due
to chronic thermal injury of the esophagus increasing the sus* H. Yamasaki and H. Bartsch, personal communication.
4J. Chang-Claude. J. Wahrendorf, S. L. Qui, G. R. Young, N. Muñoz.M.
Crespi, R. Raedsch, D. Thurnham, and P. Correa. An epidemiologie study of
chronic oesophagitis among young persons in Huixian county, Henan Province,
a high-risk area for oesphageal cancer in China, submitted for publication.
ceptibility of the esophagus to carcinogens such as those con
tained in tobacco tar. Results from the previous studies in
Uruguay and Brazil and the present one support this possibility.
A direct test of whether mate exerts its effect through direct
carcinogens or through chronic thermal injury is being carried
out in Paraguay, where the habit of drinking mate is also
widespread. There it is mainly drunk cold and the esophageal
cancer rates are lower than in Southern Brazil, Uruguay, and
northeastern Argentina.
Finally, since this study was hospital based, the possibility of
selection bias should be considered. The possibility of this bias
among cases cannot be evaluated but it was attempted among
controls. The inclusion of patients with other cancers in the
control group did not appear to affect the associations detected.
ACKNOWLEDGMENTS
We are grateful to S. Macadar and L. Torres for their assistance.
REFERENCES
1. Day, N. E., and Muñoz,N. Esophagus. In: D. Schottenfeld, and J. F.
Fraumeni (eds.). Cancer Epidemiology and Prevention, pp. 526-623. Phila
delphia: Saunders, 1982.
2. Vassallo, A., Correa, P., De Stefani. E., Cendan, M., Zavala, D., Chen, V.,
Carzoglio, J., and Deneo-Pelligrini, H. Esophageal cancer in Uruguay. A
case-control study. J. Nati. Cancer Inst., 75: 1005-1009, 1985.
3. Yu, M. C, Garabrant, D. H., Peters, J. M., and Mack, T. M. Tobacco,
alcohol, diet, occupation and carcinoma of the oesophagus. Cancer Res., 48:
3843-3848, 1988.
4. Victora, C. G., Muñoz,N., Day, N. E., Barcelos. L. B., Peccin, D. A., and
Braga, N. Hot beverages and oesophageal cancer in Southern Brazil. A casecontrol study. Int. J. Cancer, 39: 710-716, 1987.
5. Tuyns, A. J., Pequinot, G., and Jensen, O. M. Le cancer de l'oesophage en
Ule et Vilaine en fonction des niveaux de consommation d'alcohol et de
tabac. Des risques qui se multiplient. Bull. Cancer (Paris), 64: 45-60, 1977.
6. Segal, I., Reinach, S. G., and De Beer, M. Factors associated with oesopha
geal cancer in Soweto, South Africa. Br. J. Cancer, 5«:681-686, 1988.
7. Jussawalla. D. J. Oesophageal cancer in India. J. Cancer Res. Clin. Oncol.,
99:29-33, 1981.
8. Cook-Mozaffari, P. J., Azordegan, F., Day. N. E., Ressicaud, A., Sabai, C.,
and Aramesh, B. Oesophageal cancer studies in the Caspian littoral of Iran:
results of a case-control study. Br. J. Cancer, 39: 293-309, 1979.
9. Li, J. Y., Ershow, A. G., Chen, Z. J., Wacholder, S., Li, G. Y., Guo, W., Li,
B., and Blot, W. J. A case-control study of eosophageal and gastric cardia in
Linxian. Int. J. Cancer, 43: 755-761, 1989.
10. Ghadirian, P., Stein, G., Gorodetzky, D., Roberfroid, M., Mahon, G. A. T.,
Bartsch, H., and Day, N. E. Oesophageal cancer studies in the Caspian
littoral of Iran: some residual results, including opium use as a risk factor.
Int. J. Cancer, 35: 593-597, 1985.
11. Lu, S. H., Montesano, R., Zhang, M. S., Feng, L., Luo, F. J., Chui, S. X.,
Umbenhauer, D., Saffhill, R., and Rajewsky, M. I. Relevance of A'-nitrosamines to oesophageal cancer in China. J. Cell. Physiol., 4: 51-58, 1986.
12. Breslow, N. E., and Day, N. E. Statistical Methods in Cancer Research. Vol.
I. The Analysis of Case-Control Studies (IARC Scientific Publications, No.
32), p. 237. Lyon: International Agency for Research on Cancer, 1980.
13. Baker, R. J., and Neider, J. A. The GLIM System, Release 3. Generalized
Linear Interactive Modelling. Oxford: Numerical Algorithms Group, 1978.
14. Vineis, P., Esteve, J., and Terracini, B. Bladder cancer and smoking in males:
types of cigarettes, age at start, effect of stopping and interaction with
occupation. Int. J. Cancer, 34: 165-170, 1984.
15. Iscovich, J., Castelletto, R., Esteve, J., Muñoz,N., Colanzi, R., Coronel, A.,
Deamezola, I., Tassi, V., and Arslan, A. Tobacco smoking, occupational
exposure and bladder cancer in Argentina. Int. J. Cancer, 40: 734-740, 1988.
16. Tuyns, A. J., Esteve, J., Raymond, L., Berrino, F., Benhamou, E., Blanchet,
F., Boffetta, P., Crosignani, P., del Moral, A., Lehmann, W., Merletti, F.,
Pequignot, G., Riboli, E., Sancho-Garnier, H., Terracini, B., Zubiri, A., and
Zubiri, L. Cancer of the larynx/hypopharynx, tobacco and alcohol: IARC
international case-control study in Turin and Várese(Italy), Zaragoza and
Navarra (Spain), Geneva (Switzerland) and Calvados (France). Int. J. Cancer,
41:483-491, 1988.
17. De Stefani, E., Correa, P.. Greggia, F., Leiva, J., Rivero, S., Fernandez, G.,
Deneo-Pellegrini, H., Zavala, D., and Fontham, E. Risk factors for laryngeal
cancer. Cancer (Phila.), 60: 3087-3091, 1987.
18. De Stefani, E., Correa, P., Greggia, F., Deneo-Pellegrini, H., Fernandez, G.,
Zavala, D., Carzoglio, J., Leiva, J., Fontham. E., and Rivero, S. Black
tobacco, wine and mate in oropharyngeal cancer. A case-control study from
Uruguay. Revue d'Epidemiologie et de SantéPublique, 36: 389-394, 1988.
19. Patrianakos, C., and Hoffmann. D. Chemical studies of tobacco smoke.
430
Downloaded from cancerres.aacrjournals.org on June 12, 2017. © 1990 American Association for Cancer Research.
ESOPHAGEAL CANCER IN URUGUAY
20.
21.
22.
23.
24.
25.
26.
27.
LXIV: on the analysis of aromatic amines in cigarette smoke. J. Anal. Chem.,
3: 150-154, 1979.
Malaveille, C, Vineis, P., Esteve, J., Oshima, H., Brun, G., Hautefeuille, A.,
Gallet, P., Ronco, G., Terracini, B., and Bartsch, H. Levels of mutagens in
the urine of smokers of black and blond tobacco correlate with their risk of
bladder cancer. Carcinogenesis (Lond.), 10: 577-589, 1989.
Tuyns, A. J. Oesophageal cancer in non-smoking drinkers and in nondrinking smokers. Int. J. Cancer, 32: 443-444, 1983.
Mandard, A. M., Marnay, J., Helie, H., Tuyns, A. J., and Le Talaer, J. Y.
Absence of effect of ethanol and apple brandy on the upper digestive tract
and esophagus of the Wister rat. Bull. Cancer (Paris), 6«:49-58, 1981.
Horie, A., Kohehi, S., and Kunatsune, M. Carcinogenesis in the oesophagus.
II: Experimental production of oesophageal cancer by administration of
ethanolic solution of carcinogen. Gann, 56:429-441, 1965.
Wynder, E. L., and Bross, I. J. A study of etiological factors in cancers of
the esophagus. Cancer (Phila.). 14: 389-413. 1961.
Hirayama. T. Diet and cancer. Nutrition and Cancer, /: 67-81, 1971.
Tuyns, A. J., Riboli, E.. Doornbos. G., and Pequignot, G. Diet and esophageal
cancer in Calvados (France). Nutrition and Cancer, 9: 81-92, 1987.
Sugimura, T., Sato, S., and Takayama, S. New mutagenic heterocyclic amines
found in amino acid and protein pyrolysates and in cooked food. In: E. L.
Wynder, G. A. Leveille, J. H. Weisburger, and G. E. Livingston (eds.).
28.
29.
30.
31.
32.
33.
34.
Environmental Aspects of Cancer: The Role of Macro and Micro Compo
nents of Foods, pp. 167-186, Westport, CT: Food and Nutrition Press, 1983.
Segi, M. Tea-gruel as a possible factor for cancer of the esophagus. Gann,
00:199-202, 1975.
Kolycheva, N. I. Epidemiology of esophageal cancer in the USSR. In: D.
Levin (ed.). Cancer Epidemiology in the USA and USSR. Joint USA/USSR
Monograph, pp. 191-197. Washington, D.C.: NIH Publication No. 80-2044.
1980.
lARC/Iran Study Group. Esophageal cancer studies in the Caspian littoral
of Iran: results of population studies. A prodrome. J. Nati. Cancer Iusi.. 59:
1127-1138, 1977.
De Jong, U. W., Breslow, N., Goh Ewe Hong, J., Sridharan, M., and
Shanmugaratnam, K. Aetiological factors in oesophageal cancer in Singapore
Chinese. Int. J. Cancer, 13:291-303, 1974.
Martinez, I. Factors associated with cancer of the esophagus, mouth and
pharynx in Puerto Rico. J. Nati. Cancer Inst., 42: 1069-1094, 1969.
Muñoz,N., Victora, C. G., Crespi, M., Saul, C., Braga, N. M., and Correa,
P. Hot mate drinking and precancerous lesions of the oesophagus: an
endoscopie survey in southern Brazil. Int. J. Cancer. 39: 708-709, 1987.
Yioris, N., Ivankovic, S., and Lehnen, T. Effect of thermal injury and oral
administration of /V-methyl-iV'-nitro-A'-nitrosoguanidine on the development
of esophageal tumors in Wistar rats. Oncology (Basel), 41: 36-38, 1984.
431
Downloaded from cancerres.aacrjournals.org on June 12, 2017. © 1990 American Association for Cancer Research.
Mate Drinking, Alcohol, Tobacco, Diet, and Esophageal Cancer
in Uruguay
Eduardo De Stefani, Nubia Muñoz, Jacques Estève, et al.
Cancer Res 1990;50:426-431.
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