Mate Drinking, Alcohol, Tobacco, Diet, and Esophageal Cancer in … · such as Iran and China,...

[CANCER RESEARCH 50, 426-431, January 15, 1990]

Mate Drinking, Alcohol, Tobacco, Diet, and Esophageal Cancer in UruguayEduardo De Stefani, Nubia MuÃ±oz,1Jacques EstÃ¨ve,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, CoursAlbert Thomas, F-69372 Lyon cedex 08, France [N. A/., /. Â£., S. T.J; National Cancer Registry, Eduardo Acevedo No 1530, Montevideo, Uruguay [A. Y.J; andDepartamento 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 roleof mate drinking, alcohol, tobacco, and certain dietary factors in theetiology of esophageal cancer. The study included 261 patients withsquamous cell carcinoma of the esophagus and 522 hospital controlsmatched by sex and age. A strong association with a clear dose-responserelationship was observed with the amount of mate drunk daily andduration of the habit. The relative risk for those drinking over 2.5 litersof mate per day was 12.2 (95% confidence interval, 3.8-39.6) afteradjusting for the effects of age, area of residence, alcohol, and tobacco.Strong associations were also observed with tobacco smoking and alcoholdrinking which appear to act in a multiplicative way. The relative riskfor those who smoke and drink heavily compared to that of light smokersand drinkers was 22.6. The risk associated with black tobacco was aboutthree times higher than that associated with blond tobacco. A clearprotective effect was found for the consumption of fruits and vegetablesbut a dose-response relationship was present only for fruits. Finally, anincreased risk was also found for those eating barbecued meat daily.

INTRODUCTION

Esophageal cancer is characterized by worldwide geographical variation in incidence and mortality rates, even within smallareas (1). In South America, the highest rates have been reported in Uruguay, a small country which shows large variationin the rates of esophageal cancer. The mortality rates for malesrange from 40 per IO5 in the northeast region, which bordersBrazil, to 10 per 10s in the capital city of Montevideo (2). The

death rates are lower for females, with a male/female ratio of3.8 for the whole country.

Cancer of the esophagus can be divided into those cancersessentially due to alcohol and tobacco and those in which thesetwo factors do not appear to play an important part. The jointeffect of tobacco and alcohol exposures accounts for about 80%of the etiology of the disease in North America (3), SouthAmerica (2, 4), Europe (5), South Africa (6), and some Asiancountries (7).

On the other hand, in areas with extremely high incidencesuch as Iran and China, alcohol and tobacco appear to play aminor role (8, 9) and the main risk factors remain to beidentified. There is evidence suggesting that opium tar may bethe major cause in Iran (10), and yV-nitroso compounds havebeen proposed as possible etiological candidates but convincingevidence is still lacking in China (11).

Factors producing chronic injury to the esophagus, such asrough foods, hot beverages, and certain vitamin deficiencies,may increase susceptibility to carcinogens.

Esophageal thermal injury resulting from drinking hot beverages is a very difficult issue to study epidemiologically becauseof the widespread consumption of these drinks and the unreliability 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 inaccordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1To whom requests for reprints should be addressed, at International Agencyfor Research on Cancer, 150 Cours Albert-Thomas, 69372 Lyon, Cedex 08,France.

High risk areas in South America (southern region of Brazil,Uruguay, and Argentina) offer a unique opportunity to studythis problem. This is due to the fact that their populations sharethe habit of drinking large quantities of a local tea, known bythe folk name of mate. This beverage, an infusion of the herbIlex paraguayensis, is drunk very hot through a metal straw.Despite the fact that the prevalence rate of exposure is over80%, there remains a well-defined nonexposed group. A previous case-control study in Uruguay, in which routinely collected information on mate drinking was extracted from theclinical records of patients with esophageal cancer and othercancers, showed a strong association with mate drinking (RR= 4.7, 95% CI = 1.9-12.1), after adjusting for the effects of ageand alcohol and tobacco consumption (2).

Although a subsequent case-control study in southern Brazildid not show a strong association between mate drinking andesophageal cancer, the moderate increase in risk and the highprevalence of mate drinking in this population could accountfor a considerable proportion of esophageal cancers occurring(4).

This case-control study was designed to obtain further information on the hypothesis that mate ingestion is associated withthe risk of developing esophageal cancer.

SUBJECTS AND METHODS

The basic protocol utilized in the Brazilian study (4) was used in thisstudy. The Brazilian questionnaire was adapted to the local situationof Uruguay, especially in relation to type of tobacco and diet.

In the study period from July 1985 to September 1988, 283 caseswith clinical and/or radiological diagnosis of esophageal cancer wereadmitted to the four main hospitals in Montevideo. These centers havea catchment area which covers 45% of the population of Montevideoand about 55% of the rest of the country. Patients treated in thesehospitals are covered by Social Security medical care and have ratherlow incomes. Conditions for eligibility were: (a) to have histolÃ³gica!diagnosis of squamous cell carcinoma; (b) to have been diagnosedwithin the previous 4 months; (c) to have lived in the country for atleast 5 years; (</) to be in sufficiently good physical and mental healthto give reliable answers to the questionnaire. Proxy interviews were notaccepted. Cases were ascertained shortly after clinical diagnosis throughthe hospital cancer registries operating in the participating centers.

None of the patients refused to be interviewed and 15 patients wereexcluded, 12 because no histolÃ³gica! confirmation was available andthree because of a diagnosis of adenocarcinoma. Of the remaining 268patients, seven could not be interviewed due to terminal illness. Theremaining 261 patients were included in the study. For each case, twocontrols matched by age (Â±5years) and sex were interviewed. Conditions for eligibility were: (a) to be admitted to the same hospitals; (Â¿>)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 diagnosticcategories 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, andtea (quantity, duration, and temperature); alcohol drinking (dose, expressed in milliliters of alcohol, duration, and type of alcoholic beverage); and tobacco smoking (type of tobacco, duration, intensity, andcessation periods). Dietary habits were assessed in two time periods:

426

Research. on December 8, 2020. © 1990 American Association for Cancercancerres.aacrjournals.org Downloaded from

http://cancerres.aacrjournals.org/

ESOPHAGEAL CANCER [N URUGUAY

Table 1 Diagnostic categories among control patients Table 2 Distribution afeases and controls according to main risk factors

ICD-9550-553360-379574-575153-154600540-542174172-173454185200-208186-187730-731|690-698122240-541581-594210-229281-289DiagnosisInguinal

and abdominalherniasDiseasesof theeyeGallbladder

disordersColorectalcancerProstatichypertrophyAppendicitisBreast

cancerSkincancerVaricoseveinsProstaticcancerLymphoma-leukemiaCancer

of the testis and other genitaltumorsOsteomusculardiseasesOther

malignanttumorsSkindisordersHydatidcystDisorders

of the thyroidglandUrinarytractdiseasesBenign

tumorsBlooddisordersNo.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.

the period just before the onset of symptoms and 10 years beforeadmsission to the hospital. A food frequency questionnaire was used toassess the consumption of the various food items. The same 10 foodgroups used in the Brazilian questionnaire were included, i.e., freshmeat, processed meat, barbecued meat, eggs, cereals, potatoes and sweetpotatoes, 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). Anunconditional analysis was done because it is generally accepted that ina matched study, this analysis can be performed if appropriate adjustment is made for the matching variables that in this study were sex,age, and hospital. Moreover, the results obtained with the conditionalanalysis were practically identical to those obtained with the unconditional one. Relative risk estimates were approximated by odds ratiosand were calculated after adjustment either for age and residence or forage, sex, and residence when a common relative risk for male andfemale was estimated. Adjustment for residence was made because it isknown that the rates for esophageal cancer are higher in rural thanurban areas in Uruguay. Trend tests were performed by adjusting alinear model using the numbers of the categories as covariate andadjusting simultaneously for all relevant categorized cofactors. Thecontrol group was subdivided into controls with other cancers andcontrols without cancer. The statistical analysis for the main risk factorsyielded similar results for both subgroups and in addition the \ ' tests

for heterogeneity were nonsignificant. Thus both subgroups were combined in the final analysis.

RESULTS

A total of 261 cases (199 males, 62 females) and 522 controlswere included in the study. Their distribution by age, sex,residence, education (years of schooling), income, and somerisk factors is given in Table 2. Cases, especially males, aremore often rural and have lower socioeconomic status thancontrols. The association of these variables with esophagealcancer was evaluated as follows.

Effects of Alcohol and Cigarette Consumption. Tobacco smokers and alcohol drinkers were defined as those who smoked ordrank alcoholic beverages, for at least 1 year, independently ofthe amount. Cases and controls were classified according to thelifetime consumption of cigarettes and alcoholic beverages,duration and daily consumption.

The distribution of alcohol and cigarette consumption beingvery different in males and females, the evaluation of these riskfactors has been done separately for each sex. Table 3 showsthe relative risks and their CIs2 for various levels of consump-

MaleNumberAge<5455-6465-7475+ResidenceMontevideoNorthSouthUrbanRuralYears

ofstudy0-23-45-67+Income

(inpesos)<5.9996,000-11,99912,000-23,99924,000-47.999248,000Smoking

statusNonsmokerSmokerExsmokerType

oftobaccoBlackBlondMixedDrinking

habitNondrinkerCurrent

drinkerOccasionaldrinkerExdrinkerType

ofalcoholWinedrinkerSpiritdrinkerBeer

drinkerMate

statusNondrinkerCurrent

drinkerExdrinkerCase19911.6-31.137.719.620.127.152.854.845.234.730.728.16.518.624.627.120.69.13.556.839.763.822.613.69.162.83.524.681.571.713.92.080.417.6Control39814.6-31.939.215.629.420.450.368.931.127.932.431.28.513.820.125.426.414.314.140.245.738.932.728.420.647.53.828.183.659.721.89.575.415.1FemaleCase628.1'19.338.733.917.741.940.374.225.841.935.521.01.625.833.919.416.14.866.121.012.914.517.767.856.525.84.812.991.28.312.51.680.717.7Control1245.6-23.443.627.424.225.850.068.631.432.330.629.87.317.725.025.024.28.184.78.17.30.813.785.566.116.95.711.391.711.1II.

18.168.523.4

2The abbreviations used are: CI, confidence interval; RR, relative risk.

" This value and subsequent values in this column represent percentages.

tion. The risk increases significantly after an average consumption of 50 ml of pure alcohol per day in males and earlier infemales. Among the latter, however, the estimates are unstabledue to the small number of drinkers. The trend tests for testingthe effect of alcohol and tobacco are nevertheless highly significant (x2 with one degree of freedom are respectively, 4.9 and

5.5), and the interaction between tobacco, alcohol, and sex wasnot significant but the CIs were very wide. As only two femalecases and one control smoke more than seven cigarettes anddrink more than 50 ml of alcohol a day, the combined effect ofalcohol and tobacco could be evaluated only in males. In Table4 the number of nonsmokers and nondrinkers were put togetherwith those of light smokers and drinkers because the numberof the former was too small (one case and 32 controls). Table4 shows that a multiplicative model gives a good description ofthe data, but no formal test of this model could be done withthe limited number of cases available. The joint effect of duration of tobacco smoking and alcohol consumption yielded similar results with a less good Tit.

The risk for esophageal cancer decreased significantly among427



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

(perday)01-78-1415-24

25+Alcohol

(ml perday)01-2425-4950-149150-249250+No.

cases7142862

88261612504649No.

controls565475101

11210061511173831Adjusted

RR11.93(0.7-5.4)2.66(1.1-6.8)4.26(1.7-10.4)

4.62(1.9-11.1)10.85(0.4-1.8)0.71

(0.3-1.6)1.37(0.8-2.4)3.57(1.9-6.7)5.27(2.7-10.2)No.

cases4111â€¢381212FemalesNo. controls105118882412AdjustedRR]2.27

(0.9-6.0)3.22(1.11-9.3)1.04(0.4-2.4)1.89(0.7-4.9)

Table 4 Age and residence-adjusted relative risks for the joint effect of alcoholand tobacco consumption

Alcohol(ml perday)0-4950-149150-249250-349350+Total

(RR for cigarette)Cigarettes

perday0-71(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(22)30.0(6)22.6(20)3.1(88)Total(RR foralcohol)1(54)1.6(50)4.1(46)5.1(16)6.7(33)(199)

male exdrinkers (P = 0.01) and there was a significant trendwith years since quitting: the RR values adjusted for age,residence, and amount of cigarettes per day, with the regulardrinkers as reference category, were as follows: 1-9 years sincequitting 0.78 (95% CI, 0.48-1.26), >10 years 0.46 (0.23-0.92),nondrinkers and occasional drinkers 0.48 (0.29-0.81) (P =

0.001).Influence of the Type of Alcoholic Beverage. The distribution

of type of alcohol consumed by the study subjects changes withtheir total consumption of alcohol; as a consequence, thisdistribution differs between cases and controls. Light drinkerstend to drink more beer and wine and less spirits than heavydrinkers. On the other hand, heavy drinkers tend to drink morespirits than light drinkers. Since total alcohol consumption isgiven by the sum of the three types of alcoholic beverages, theaverage linear increase for each of them separately was calculated adjusting for the others and considering each beverage asa continuous variable. There was a significant difference ofeffect between beverages. Beer did not contribute to the risk,whereas wine and hard liquor increased the risk by the sameamount for each milliliter of pure alcohol added. Therefore, inthis population, the sum of liquor and wine consumption is abetter indicator of the risk associated with alcohol consumptionthan total alcohol.

Influence of Other Smoking Variables (Male Smokers Only).When adding to the multiplicative model including age, residence, and average cigarette and alcohol consumption, age atstart (four categories), number of years since quitting (fivecategories), and duration (five categories), no effect of age atstart was found, but years since quitting smoking and durationwere found to modify significantly the risk. The assessment oftobacco exposure by duration gives a better fit than the average

number of cigarettes per day (data not shown).As shown in Table 2, most of the male smokers in Uruguay

smoked either black or blond tobacco. Black tobacco was usedby 69% of male smoker cases against 47% among controls. Inaddition, 64% of cases and 40% of controls smoked blacktobacco only. This difference was highly significant after controlling for daily dose of alcohol and tobacco. The risk for thosewho have smoked mainly black tobacco compared to that ofthose who smoked mainly blond tobacco was 2.6 (95% CI, 1.7-3.9). For mixed smokers, mainly black tobacco smokers werethose who have smoked more black tobacco than blond tobaccoover their life-span. Moreover, the effect of type of tobaccocombines multiplicatively with duration of smoking (Table 5).

Among male smoker patients, 19% used filter cigarettesagainst 28% among controls. This apparent protective effect offilters was however no longer significant after adjustment foralcohol, cigarette consumption, and type of tobacco: the use offilter cigarettes was in fact similar in cases and controls afterstratification by type of tobacco.

No cases or controls used pipes or cigars.Dietary Factors. In the following analyses, all risk evaluations

were made after adjustment for age, sex, region, alcohol, duration of cigarette smoking, and type of tobacco smoked. Thecurrent and past frequencies of consumption of the 10 foodgroups were compared between cases and controls and nosignificant differences were found. Therefore the current consumption was used in the analysis. The 10 food groups werefresh meat, preserved meat, barbecued meat, fat, dairy products,eggs, cereals, potatoes, vegetables, and fresh fruits. Table 6reports the results for those food groups which have beensuspected of influencing the risk of esophageal cancer. A clearprotective effect and a significant dose-response relationshipwas found with the consumption of fresh fruits. A reduction inrisk was also observed with the consumption of vegetables butwithout significant dose response. A significant increase in risk

Table 5 Age, residence, and alcohol adjusted relative risks (95% Cl)Â°for

duration of smoking and type of tobacco (males only)

Duration ofcigarette smoking

(years)1-2425-44

45+Type

oftobaccoMainly

blond1

2.54.4Mainly

black3.2

8.19.0Duration

(years)adjusted for

type oftobacco*1

2.5(1.1-5.7)3.3(1.5-7.3)

Type of tobacco adjusted 1 2.6(1.7-3.9)for duration" The estimation was carried out within the set of male smoker cases and

controls."The x1 for interaction between the two factors is 1.15 with 2 df.

428




Table 6 Adjusted relative risks for the current consumption of certain food stuffs DISCUSSION

Food0Fresh

meatFatVegetablesBarbecued

meatFruits<

oncea week111111-3

limes/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

times/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)Trend(x)2.112.27-2.451.73-4.58

" Adjusted for age, residence, smoking duration, type of tobacco, and alcohol

consumption.

Table 7 Adjusted relative risks for mate drinking0

Daily amountliters/day00.01-0.490.50-1.491.50-2.492.50+Duration

(years)0-1415-2930-4445-5960+Number

ofcases51113378347115810184Number

ofcontrols48443179518623410423092Adjusted

RR(95%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)

" Adjusted for sex, age, residence, alcohol, smoking duration, and type of

tobacco.

for those who eat barbecued meat daily was observed butwithout a significant dose-response relationship. However, theincrease in risk for those who eat barbecued meat daily persistedafter adjusting for meat consumption. No clear effect for freshmeat and fat and no significant associations with the other foodgroups were observed.

Mate Drinking. Mate drinking is very common in Uruguay.Only 9% of controls and 2% of cases were nondrinkers. Therewas a clear dose-effect relationship between amount of matedrunk each day and the risk of esophageal cancer (Table 7).There was also a less convincing but significant relation withduration of use. The slope of the dose-effect relationship wasthe same for both sexes in each alcohol consumption categoryand in all smoking categories. There was, however, a significantabsence of effect among blond tobacco smokers (x2 = 8.3 on 2

df). There was no significant interaction with any other availablefactor. The slope of the dose-effect plot was larger among therural population, but not significantly so.

Interaction terms for tobacco smoking, alcohol and matedrinking, and socioeconomic status were calculated and foundnonsignificant as expected from the size of the study.

Influence of Temperature of Hot Beverages. The reportedtemperature of beverages other than mate was not associatedwith the risk of esophageal cancer. The temperature of matehad a nonconsistent significant effect: the slope of the dose-effect relationship was lower among people who reported hotmate drinking, and higher and identical among those who reportwarm or very hot. The effect of dose of mate was neverthelesssignificant in the three categories of drinkers.

It is estimated that about 40% of all esophageal cancer casesoccurring in Uruguay during the study period were included inour study. However, the degree of representativeness of thestudy cases cannot be evaluated. With this limitation in mindwe can say that our results indicate that 90% of the cases ofesophageal cancer occurred over the age of 55 and that casestended to live in rural areas and to have a lower socioeconomicstatus than the controls, which is in agreement with observations in other populations (4, 6). With regard to etiology, thisstudy revealed that, as in similar studies carried out earlier inUruguay (2) and in Brazil (4), alcohol and tobacco are the mainrisk factors for this cancer and that these two factors appear toact in a multiplicative way. The relative risk for those who bothdrink and smoke heavily (over 250 ml of alcohol/day and over25 cigarettes/day) was about 20, which was less than thatreported from France (5). As regards tobacco, this populationoffers a special opportunity to compare the effects of the twotypes of tobacco, as approximately half smoke blond, flue-curedtobacco and the other half smoke black, air-cured tobacco. Therisk for smokers of black tobacco cigarettes was increasedalmost threefold compared to that of smokers of blond tobaccocigarettes and it increased even more with duration than withthe number of cigarettes smoked. These findings are in agreement with results from case-control studies on bladder cancerin Italy (14), Argentina (15), on laryngeal cancer in southernEurope (16) and previous studies on cancers of larynx andoropharynx in Uruguay (17, 18), suggesting that black tobaccois more carcinogenic than blond tobacco. Moreover, these observations are reinforced by laboratory results showing that thesmoke of black tobacco cigarettes contained more aromaticamines and tobacco-specific nitrosamines than that from blond

tobacco cigarettes (19) and that the urine of smokers of blacktobacco contained about twice as much mutagenic activity asdid the urine of blond cigarette smokers (20).

In relation to alcohol, the risk increases more with theamount of alcohol consumed than with the number of cigarettessmoked, which is in agreement with the observations made inthe high risk areas for esophageal cancer in France (5). As inthe French studies, the correlation is essentially with theamount of alcohol consumed and not with the type of alcoholicbeverage. In Uruguay, the magnitude of the increase in riskassociated with the consumption of spirits in males was similarto that associated with wine drinking, which is not surprisingconsidering that about 80% of the male drinkers are winedrinkers and 60% are drinkers of spirits. However, no increasedrisk associated with the consumption of beer could be detectedbecause there are very few beer drinkers among the male drinkers (20%). In contrast with the epidemiological studies whichshow that alcohol clearly increases the risk for esophagealcancer even among nonsmokers (21), the laboratory studieshave yielded negative results (22). It has long been suggestedthat alcohol may act as a solvent facilitating the transport ofcarcinogens through the esophageal mucosa (23), but it mayalso act as a chronic irritant, raising the susceptibility to carcinogens by accelerating cell turnover and thus favoring contactbetween the carcinogens and the dividing target cells (1).

Concerning dietary factors, a clear protective effect and adose-response relationship was observed for the consumptionof fruits, which is in agreement with observations made in otherpopulations (3, 4, 8, 24, 25). Although a protective effect ofvegetables was also detected, no dose-response relationship wasobserved. Unfortunately, no distinction was made between raw

429




and cooked vegetables. No clear effect of fresh meat was found.A protective effect was found in France (26), but an increasedrisk has been associated with fresh meat in Brazil (4). A clearincrease in risk was observed for those eating barbecued fooddaily compared to those eating them less frequently, even afteradjusting for meat consumption. This observation is contraryto the findings of a similar case-control study carried out in aneighboring area (4), but it is consistent with laboratory investigations showing the presence of animal carcinogens and mu-tagens in barbecued foods formed by the pyrolysis of proteins(27).

The present study was designed to study further the association with mate drinking. A strong association with a clear dose-response relationship was observed with the amount of matedrunk daily. The RR for those drinking over 2.5 liters per daywas 12.2 (95% CI, 3.8-39.6), after adjusting for age, tobacco,and alcohol. A less strong and less clear dose-response relationship was observed with duration of the habit. The fact that themate effect was present among nonsmokers and light smokers,and among smokers of black tobacco but not smokers of blondtobacco, is puzzling. The possibility that blond tobacco smokerswere from a higher socioeconomic level and had a higher intakeof fruit and vegetables was considered, especially in view of agreater effect of mate drinking among the rural population, butit was not confirmed. The finding of a significant but notconsistent effect of the temperature at which mate is drunk isnot surprising considering the subjectivity in the perception oftemperature. To evaluate the degree of misclassification in thereported temperature at which mate is drunk, a validation studyis being carried out in Southern Brazil and in Montevideo.

There are two possible mechanisms through which matedrinking could increase the risk of esophageal cancer. First, theplant extract may contain carcinogenic or promoting substances. This possibility was raised in a previous study carriedout in Uruguay (2), but laboratory studies have so far notdemonstrated any promoting or mutagenic activity.3

Secondly, hot mate drinking may increase the susceptibilityof the esophagus to carcinogens. Several epidemiological studies point towards a possible effect of hot drinks on esophagealcancer incidence. Ecological studies from Japan (28), the SovietUnion (29), and northern Iran (30) have suggested that inhabitants of high risk areas drink larger quantities of hot tea thanthose of low risk areas. Also in Iran, Singapore, and PuertoRico case-control studies indicated similar differences (8, 31,32). A prospective study carried out in Japan (25) also showeda higher risk among those drinking hot green tea.

A possible effect of mate drinking on precancerous lesions ofthe esophagus has been demonstrated in an endoscopie surveycarried out in Rio Grande do Sul (33). In addition, in a recentstudy on chronic esophagitis among young subjects in a highrisk population for esophageal cancer in China, the strongestrisk factor found for esophagitis was the consumption of beverages at burning hot temperatures.4

Experimental animal data suggest that hot drinks may potentiate the effect of esophageal carcinogens (34). The above observations, and in particular the finding that mate drinkingincreases the risks of esophagitis, suggest that mate itself maynot contain specific carcinogens but that its effect may be dueto 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. MuÃ±oz.M.

Crespi, R. Raedsch, D. Thurnham, and P. Correa. An epidemiologie study ofchronic 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 contained in tobacco tar. Results from the previous studies inUruguay and Brazil and the present one support this possibility.

A direct test of whether mate exerts its effect through directcarcinogens or through chronic thermal injury is being carriedout in Paraguay, where the habit of drinking mate is alsowidespread. There it is mainly drunk cold and the esophagealcancer rates are lower than in Southern Brazil, Uruguay, andnortheastern Argentina.

Finally, since this study was hospital based, the possibility ofselection bias should be considered. The possibility of this biasamong cases cannot be evaluated but it was attempted amongcontrols. The inclusion of patients with other cancers in thecontrol 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 MuÃ±oz,N. Esophagus. In: D. Schottenfeld, and J. F.Fraumeni (eds.). Cancer Epidemiology and Prevention, pp. 526-623. Philadelphia: 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. Acase-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., MuÃ±oz,N., Day, N. E., Barcelos. L. B., Peccin, D. A., andBraga, N. Hot beverages and oesophageal cancer in Southern Brazil. A case-control study. Int. J. Cancer, 39: 710-716, 1987.

5. Tuyns, A. J., Pequinot, G., and Jensen, O. M. Le cancer de l'oesophage enUle et Vilaine en fonction des niveaux de consommation d'alcohol et detabac. 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 oesophageal cancer in Soweto, South Africa. Br. J. Cancer, 5Â«: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 inLinxian. 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 Caspianlittoral 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'-nitrosa-mines 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. GeneralizedLinear 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 withoccupation. Int. J. Cancer, 34: 165-170, 1984.

15. Iscovich, J., Castelletto, R., Esteve, J., MuÃ±oz,N., Colanzi, R., Coronel, A.,Deamezola, I., Tassi, V., and Arslan, A. Tobacco smoking, occupationalexposure 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., andZubiri, L. Cancer of the larynx/hypopharynx, tobacco and alcohol: IARCinternational case-control study in Turin and VÃ¡rese(Italy), Zaragoza andNavarra (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 laryngealcancer. 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. Blacktobacco, wine and mate in oropharyngeal cancer. A case-control study fromUruguay. Revue d'Epidemiologie et de SantÃ©Publique, 36: 389-394, 1988.

19. Patrianakos, C., and Hoffmann. D. Chemical studies of tobacco smoke.

430




LXIV: on the analysis of aromatic amines in cigarette smoke. J. Anal. Chem.,3: 150-154, 1979.

20. Malaveille, C, Vineis, P., Esteve, J., Oshima, H., Brun, G., Hautefeuille, A.,Gallet, P., Ronco, G., Terracini, B., and Bartsch, H. Levels of mutagens inthe urine of smokers of black and blond tobacco correlate with their risk ofbladder cancer. Carcinogenesis (Lond.), 10: 577-589, 1989.

21. Tuyns, A. J. Oesophageal cancer in non-smoking drinkers and in non-drinking smokers. Int. J. Cancer, 32: 443-444, 1983.

22. 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 tractand esophagus of the Wister rat. Bull. Cancer (Paris), 6Â«:49-58, 1981.

23. Horie, A., Kohehi, S., and Kunatsune, M. Carcinogenesis in the oesophagus.II: Experimental production of oesophageal cancer by administration ofethanolic solution of carcinogen. Gann, 56:429-441, 1965.

24. Wynder, E. L., and Bross, I. J. A study of etiological factors in cancers ofthe esophagus. Cancer (Phila.). 14: 389-413. 1961.

25. Hirayama. T. Diet and cancer. Nutrition and Cancer, /: 67-81, 1971.26. Tuyns, A. J., Riboli, E.. Doornbos. G., and Pequignot, G. Diet and esophageal

cancer in Calvados (France). Nutrition and Cancer, 9: 81-92, 1987.27. 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.).

Environmental Aspects of Cancer: The Role of Macro and Micro Components of Foods, pp. 167-186, Westport, CT: Food and Nutrition Press, 1983.

28. Segi, M. Tea-gruel as a possible factor for cancer of the esophagus. Gann,00:199-202, 1975.

29. Kolycheva, N. I. Epidemiology of esophageal cancer in the USSR. In: D.Levin (ed.). Cancer Epidemiology in the USA and USSR. Joint USA/USSRMonograph, pp. 191-197. Washington, D.C.: NIH Publication No. 80-2044.1980.

30. lARC/Iran Study Group. Esophageal cancer studies in the Caspian littoralof Iran: results of population studies. A prodrome. J. Nati. Cancer Iusi.. 59:1127-1138, 1977.

31. De Jong, U. W., Breslow, N., Goh Ewe Hong, J., Sridharan, M., andShanmugaratnam, K. Aetiological factors in oesophageal cancer in SingaporeChinese. Int. J. Cancer, 13:291-303, 1974.

32. Martinez, I. Factors associated with cancer of the esophagus, mouth andpharynx in Puerto Rico. J. Nati. Cancer Inst., 42: 1069-1094, 1969.

33. MuÃ±oz,N., Victora, C. G., Crespi, M., Saul, C., Braga, N. M., and Correa,P. Hot mate drinking and precancerous lesions of the oesophagus: anendoscopie survey in southern Brazil. Int. J. Cancer. 39: 708-709, 1987.

34. Yioris, N., Ivankovic, S., and Lehnen, T. Effect of thermal injury and oraladministration of /V-methyl-iV'-nitro-A'-nitrosoguanidine on the developmentof esophageal tumors in Wistar rats. Oncology (Basel), 41: 36-38, 1984.

431



1990;50:426-431. Cancer Res Eduardo De Stefani, Nubia Muñoz, Jacques Estève, et al. in Uruguay

Drinking, Alcohol, Tobacco, Diet, and Esophageal CancerMate

Updated version

http://cancerres.aacrjournals.org/content/50/2/426

Access the most recent version of this article at:

E-mail alerts related to this article or journal.Sign up to receive free email-alerts

Subscriptions

Reprints and

[email protected] at

To order reprints of this article or to subscribe to the journal, contact the AACR Publications

Permissions

Rightslink site. Click on "Request Permissions" which will take you to the Copyright Clearance Center's (CCC)

.http://cancerres.aacrjournals.org/content/50/2/426To request permission to re-use all or part of this article, use this link



http://cancerres.aacrjournals.org/cgi/alerts

mailto:[email protected]



Mate Drinking, Alcohol, Tobacco, Diet, and Esophageal Cancer in … · such as Iran and China,...

Documents

Transcript of Mate Drinking, Alcohol, Tobacco, Diet, and Esophageal Cancer in … · such as Iran and China,...