Hot and Cold Mate Drinking and Esophageal Cancer in Paraguay

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
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
Received 2/9/95; revised 5/12/95; accepted 5/15/95.
I To
whons
requests
for reprints
should
he addressed.
Esophageal
Epidemiology,
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
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 October 30, 2016. © 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 October 30, 2016. © 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
0.88
(38.1)
33
(61.9)
25
(52.4)
(7.9)
(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 October 30, 2016. © 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:
<0.00001,
for the effect
of duration,
and
0.0002,
for the effect
of amount).
Downloaded from cebp.aacrjournals.org on October 30, 2016. © 1995 American Association for Cancer Research.
Cancer
Table
3
Effect
of selected
s moking-
related
Cases
variables
OR1”
Pt
I cancer
Biomarkers
risk
(%)
(95%
CI)
OR,”
18
(13.7)
184
(48.3)
1.0
Past
35
(26.7)
80
(21.0)
5.5
(2.8-10.9)
3.6
Current
78
(59.5)
117
(30.7)
8.5
(4.6-15.7)
4.5
1.0
no.
(2.2-9.1)
0(85)06
of cigarettes
18
(13.7)
184
(48.3)
1.0
1-14
56
(42.7)
148
(38.8)
5.1
(2.7-9.7)
3.2
(1.6-6.5)
15-39
46
(35.1)
40
(10.5)
16.7
(8.0-34.7)
8.4
(3.6-19.3)
40
11
(8.4)
(2.4)
16.5
(5.6-48.2)
6.1
P for trend
Lifetime
(smokers
9
1.0
only)
(1.8-20.8)
0.01
no. of cigarettes
0
18
(13.7)
(48.3)
1.0
I
15
(11.4)
73
(19.2)
2.7
(1.2-5.9)
1.8
(0.7-4.2)
50,()00
16
(12.2)
53
(13.9)
5.2
(2.3-12.1)
3.4
(1.4-8.5)
l(X),()00
48
(36.6)
51
(13.4)
15.7
(7.4-33.2)
9.1
(4.0-21.0)
300,00()
34
(26.0)
20
(5.2)
28.5
(12.3-66.1)
10.0
P for trend
(smokers
184
1.0
only)
(3.9-25.8)
<0(888)1
of smoking
(1
18
(13.7)
184
(48.3)
1.0
1-29
15
(11.4)
64
(16.8)
2.4
(1.1-5.4)
1.5
(0.6-3.7)
3(5-39
4))
31
67
(23.7)
(51.1)
51
(13.4)
7.4
(3.6-15.2)
4.4
(1.9-10.0)
82
(21.5)
15.6
(7.6-32.1)
7.3
P for trend
Years
since
(smokers
stopped
1.0
only)
(3.3-16.3)
0.00(8)1
smoking
Nonsmoker
18
(13.7)
(48.3)
1.0
20+
4
(3.1)
16
(4.2)
3.0
(0.9-10.5)
2.0
(0.5-7.9)
8-19
6
(4.6)
27
(7.1)
2.9
(1.0-8.5)
2.0
(0.6-6.7)
1-7
25
(19.1)
37
(9.7)
8.2
(3.8-17.5)
5.2
(2.2-12.4)
Current
78
(59.5)
117
(30.7)
8.5
(4.6-15.7)
4.5
P for trend
Type
(quitters
of tobacco
smoker
184
1.0
only)
(smokers
(2.2-9.2)
0.06
only)
Mainly
black
87
(77.0)
140
(71.1)
1.0
Mainly
blond
14
(12.4)
39
(19.8)
0.5
(0.2-1.0)
0.5
(0.2-1.1)
1.4
(0.5-4.0)
1.0
(0.3-3.4)
Black
and
Blond
Unknown
OR1.
OR2,
(1.6-7.9)
0
Yrs
CI)
status
Never
Daily
I’
(95%
(%)
n
P for trend
“
& Prevention
Controls
Variables
Smoking
on esophagea
Epidemiology,
adjusted
adjusted
for design
for design
variables
variables
age group,
and lifetime
8
(7.1)
8
(4.1)
4
(3.5)
10
(5.1)
sex, and
ethanol
hospital
group.
consumption.
For
type
Alcohol.
Alcohol
drinking
was found to be the strongest
risk
factor for esophageal
cancer
risk in this population
(Table
4).
Even moderate
ethanol
drinkers
had a large excess
in risk as
compared
to nondrinkers.
Although
amount
and, to a lesser
extent,
quitting
showed
a dose-response
relationship
with risk,
no trend with years of alcohol
consumption
was found.
Thus,
shortand long-term
drinkers
had a similar
excess
in risk.
When
adjusting
average
daily amount
and duration
simultaneously,
only
the effect
of amount
remained
statistically
significant
(P value
for
the
likelihood
ratio
statistic,
<0.00001;
corresponding
P value
for duration,
0.6). Quitting alcohol
drinking
was clearly
beneficial,
and the risk
ratio of long-term
to short-term
quitting
was about
3. Nevertheless,
alcohol
had a persistent
long-term
effect and even
quitting
alcohol
drinking
for >15
years was still associated
with a 4-fold
excess
in risk. Beer and wine,
less frequently
consumed
in this population,
were
not associated
with an
increased
risk.
Joint Effect
bined
effects
multivariate
of Alcohol
and Tobacco.
We assessed
the comof tobacco
and alcohol
amounts
by fitting
a
model,
which
included
the design
variables,
the
of tobacco,
adjusted
in addition
1.0
for lifetime
number
of cigarettes
smoked.
main effect terms for alcohol
and tobacco,
and an interaction
term between
the two. Although
the interaction
was not statistically significant
suggesting
no departure
from the usual multiplicative
model
(P = 0.15),
increasing
exposure
to both
factors
was associated
with higher
risks. Thus, as compared
to
subjects
never
exposed
to tobacco
and alcohol,
nonsmokers
who drank > 150 ml/day of ethanol
had an OR of 83.2 (95% CI
=
I 1.1-624.9);
if, in addition
to drinking
this
amount,
they
smoked
an average
of 15-40
cigarettes/day
the OR increased
to
284.0 (95% CI - 62.5-1291.0).
Diet. Table 5 summarizes
the main dietary
findings
of current
consumption
using two different
multivariate
models.
First, the
effect of each separate
food group was assessed
adjusting
for
the design variables
and ethanol
and tobacco
consumption.
By
using this model
(Table
5,
OR1) strong positive
associations
were found with increasing
consumption
of fats and red meats
(both, all red meats, and beef alone) and, to a lesser extent, with
fish and milk. In an attempt
to control
for other dietary
confounders
a second
model
was fitted (Table
5, OR,),
which
additionally
included
these
four significant
food groups
as
covariates.
As shown
in Table 5, although
the strong
effects
of
Downloaded from cebp.aacrjournals.org on October 30, 2016. © 1995 American Association for Cancer Research.
599
6(X)
Male
Drinking
and
Esophageal
Cancer
in Paraguay
Table
4
Effect
of selected
alcohol-related
variables
OR1”
‘I
cancer
risk
Controls
Cases
Variables
Alcohol
on esophageal
(%)
C
(95%
CI)
OR’
16
(12.2)
202
(53.0)
1.0
Past
35
(26.7)
45
(11.8)
16.1
(7.3-35.4)
10.3
(4.4-23.9)
<I/week
12
(9.2)
27
(7.1)
9.5
(3.7-24.7)
5.9
(2.1-16.8)
I/week
68
(51.9)
(28.1)
13.))
(6.3-26.9)
8.0
Spirit
107
1.0
status
Never
30
(22.9)
275
(72.2)
1.0
Ever
101
(77.1)
103
(27.0)
14.0
Ethanol
amount
9.6
(5.2-17.8)
(0.8)
(mI/day)
16
(12.2)
202
(53.0)
1.0
I
35
(26.7)
107
(28.1)
6.7
(3.1-14.5)
4.5
(2.0-10.1)
25
15
(1 1.5)
28
(7.3)
12.3
(4.8-31.1)
7.7
(2.8-20.9)
SO
23
(1 1.6)
28
(7.3)
18.8
(7.8-45.4)
1 1.7
(4.6-30.0)
l50
42
(32.1)
13
(3.4)
77.1
(30.0-198)
37.2
(13.7-101)
3
(0.8)
Ethanol
(1
(drinkers
amount
1.0
<0.00001
only)
(lifetime
liters)
Nondrinkers
16
(12.2)
202
(53.0)
1.0
I
12
(9.2)
51
(13.4)
4.4
(1.8-11.1)
3.7
(1.4-9.7)
SO
7
(9.2)
27
(7.1)
6.2
(2.0-18.6)
3.9
(1.2-12.2)
104)
17
(13.0)
34
(8.9)
10.6
(4.3-26.6)
5.5
(2.1-14.6)
30))
22
(16.8)
38
(10.0)
12.8
(5.4-30.3)
7.8
(3.1-19.9)
I00()
57
(43.5)
26
(6.8)
50.3
(21.7-116)
27.2
3
(0.8)
0
Unknown
P for trend
Alcohol
(drinkers
duration
1.0
only)
(11.2-65.9)
<0.00001
(yrs)
Nondrinkers
16
(12.2)
202
(53.0)
1.0
I
23
(17.6)
46
(12.1)
10.1
(4.3-23.7)
8.0
(3.1-20.5)
25
48
(36.6)
60
(15.7)
15.5
(7.3-33.0)
9.1
(4.0-20.4)
40
44
(33.6)
70
(18.4)
14.0
(6.3-31.0)
8.1
(3.5-18.8)
Unknown
since
3
(4
P for trend
(drinkers
stopped
1.0
(0.8)
only)
0.78
alcohol
Nondrinkers
16
(12.2)
(53.0)
1.0
15+
3
(2.3)
11
(2.9)
5.6
(1.3-23.8)
4.3
(0.9-20.4)
6-14
4
(3.1)
9
(2.4)
8.9
(2.3-34.8)
7.0
(1.6-30.7)
1-S
28
(21.4)
25
(6.6)
23.4
(9.9-54.9)
13.5
(5.4-33.7)
Current
80
(61.1)
134
(35.2)
12.4
(6.1-25.4)
7.7
P for trend
adjusted
adjusted
(quitters
202
only)
for design
for design
variables
variables
consumption
of
lemons
1.0
(3.6-16.5)
(1.14
age group,
and lifetime
sex, and
cigarette
hospital
group.
consumption.
red meats and fats remained
with statistical
significance,
those
for fish and milk were closer
to the null value and were not
significant.
On the other
hand, high consumption
of cheese,
cereals,
and cereal
products
were all associated
with a moderately decreased
risk. High consumption
of vegetables
and citrus
fruits,
assessed
as food groups,
were both associated
with a
slight but nonsignificant
decrease
in risk. Of the citrus fruits,
daily
1.0
(7.9-24.8)
Nondrinker
P for trend
OR1.
OR,,
3
0
Unknown
F,
(3.7-17.3)
0.00002
Unknown
,‘
CI)
status
Never
P for trend
Yrs
(95%
(%)
showed
a statistically
significant
protective
effect
(OR
0.3; 95% CI
0.2-0.8),
and daily
consumption
of oranges
was associated
with a nonsignificant
protective
effect (OR = 0.6; 95%
CI = 0.2-1.4).
Nonsignificant moderately
increased
risks were detected
for high consumption
of barbecued
meat (churrasco
or asado,
OR
1.4
and 95% CI = 0.7-2.8)
and for always
adding salt to foods (OR
=
1.4; 95% CI
0.5-3.3).
No association
was found for the
kind of material
used for broiling
and roasting
(wood,
coal, or
other).
Analyses
of past consumption
of the same food groups
yielded
virtually
the same results
(data not shown).
Discussion
Hot and Cold Mate.
To our knowledge
this is the first study
in which the association
between
cold mate drinking
and esophageal cancer
is explored.
Although
hot mate drinking
has been
classified
as probably
carcinogenic
to humans
it is unknown
whether
the potential
carcinogenic
effect is due to the composition of the beverage,
to the temperature
at which
it is consumed,
or to both (10). Our study
in Paraguay
offered
an
unusual
opportunity
for assessing
further
the role of mate
drinking
because
mate is drunk
both cold and hot. However,
because
practically
all mate drinkers
were exposed
to both hot
and cold mate it was not possible
to entirely
disentangle
their
effects.
After adjusting
for the strong
effects
of tobacco
and
alcohol,
no association
was found between
the amount
or duration
of the habit of drinking
either
hot or cold mate and
esophageal
cancer
risk. However,
a significant
association
was
found with the temperature
at which
mate was drunk.
Those
Downloaded from cebp.aacrjournals.org on October 30, 2016. © 1995 American Association for Cancer Research.
Cancer
Table
5
Adjusted
effects
Cases
of dietary
food
groups
on esophageal
cancer
Epidemiology,
Biomarkers
& Prevention
risk
Controls
Variables
OR,”
(95%
CI)
OR2”
(95%
n
(%)
Lowest
14
(10.7)
1 10
(29.0)
1.0
Low
33
(25.2)
92
(24.3)
3.8
(1.6-9.3)
3.1
(1.2-7.8)
High
41
(31.3)
91
(24.0)
4.3
(1.8-10.3)
3.0
(1.2-7.5)
Highest
43
(32.8)
86
(22.7)
5.7
(2.3-13.8)
3.8
(1.3-11.0)
Red
meats
n
CI)
(%)
(all)
P for trend
1.0
0.0002
0.02
Beef
Lowest
14
(10.7)
81
(21.4)
1.0
Low
20
(15.3)
1 12
(29.6)
1.4
(0.6-3.6)
1.8
(0.6-5.0)
High
97
(74.0)
185
(48.9)
4.6
(2.1-10.3)
4.7
(2.0-11.5)
P for trend
1.0
<0.0001
0.0001
Fats
Lowest
33
(25.2)
97
(25.6)
1.0
Low
28
(21.4)
88
(23.2)
1,2
(0.6-2.6)
1.0
(0.4-2.2)
High
15
(11.5)
124
(32.7)
0.5
(0.2-1.2)
0.5
(0.2-1.3)
Highest
55
(42.0)
70
(18,5)
3.0
(1.5-6.0)
2.4
(1.1-4.9)
P for trend
1.0
0.005
0.03
Fish
Lowest
35
(27.1)
151
(40.2)
1.0
Low
31
(24.0)
74
(19.7)
2.5
(1.2-5.3)
2.0
(0.9-4.4)
High
35
(27.1)
95
(25.3)
2.6
(1.3-5.4)
2.0
(0.9-4.3)
Highest
28
(21.7)
56
(14.9)
2.7
(1.2-5.9)
1.5
(0.6-4.0)
P for trend
1.0
0.005
0.15
Milk
Lowest
32
(24.4)
101
(27.2)
1.0
Low
19
(14.5)
83
(22.3)
1.1
(0.5-2.5)
0.8
(0.3-1.9)
High
80
(61.1)
188
(50.5)
1.9
(1.0-3.5)
1.2
(0.6-2.4)
P for trend
1.0
0.03
0.51
Cheese
Lowest
45
(34.4)
89
(23.5)
1.0
Low
30
(22.9)
98
(25.9)
0.7
(0.3-1.4)
0.5
(0.2-1.2)
High
19
(14.5)
98
(25.9)
0.4
(02-0.9)
0.3
(0.1-0.6)
Highest
37
(28.2)
94
(24.8)
0.8
(0.4-1.7)
0.3
(0.1-0.7)
P for trend
1.0
0.50
0.002
Cereals
Lowest
40
(30.5)
82
(21.6)
1.0
Low
24
(18.3)
106
(28.0)
0.7
(0.3-IS)
0.7
(0.3-1.7)
High
32
(24.4)
75
(19.8)
1.1
(0.5-2.2)
1.0
(0.4-2.4)
Highest
35
(26.7)
116
(30.6)
0.6
(0.3-1.2)
0.3
(0.1-0.7)
P for trend
Cereal
1.0
0.33
0.02
products
Lowest
31
(23.7)
122
(32.0)
1.0
Low
28
(21.4)
76
(19.9)
1.8
(0.8-3.9)
1.8
(0.8-4.3)
High
40
(30.5)
74
(19.4)
1.2
(0.6-2.5)
1.0
(0.5-2.3)
Highest
32
(24.4)
109
(28.6)
0.9
(0.4-1.8)
0.4
(0.2-0.9)
P for trend
1.0
0.59
0.04
Vegetables
Lowest
30
(22.9)
86
(22.7)
1.0
Low
34
(26.0)
102
(26.9)
0.8
(0.4-1.7)
0.7
(0.3-1.6)
High
29
(22.1)
99
(26.1)
1.2
(0.5-2.4)
0.9
(0.4-2.0)
Highest
38
(29.0)
92
(24.3)
1.5
(0.7-3.1)
0.8
(0.3-1.8)
P for trend
Citrus
1.0
0.20
0.71
fruits
Lowest
39
(29.8)
96
(25.3)
1.0
Low
20
(15.3)
90
(23.7)
0.7
(0.3-1.6)
1.0
(0.4-2.4)
High
37
(28.2)
99
(26.1)
0.9
(0.4-1.8)
0.6
(0.3-1.4)
Highest
35
(26.7)
94
(24.8)
1.0
(0.5-1.9)
0.8
(0.4-1.7)
P for
trend
1.0
0.98
0.43
Downloaded from cebp.aacrjournals.org on October 30, 2016. © 1995 American Association for Cancer Research.
601
602
Male
Drinking
and
Esophageal
Cancer
in Paraguay
Table
OR1”
--
n
Noncitrus
Continued
Controls
Cases
Variables
5
(%)
n
(95%
I,
OF2,
(95%
OR,1’
1.0
33
(25.2)
93
(24.5)
1.0
Low
25
(19.1)
104
(27.4)
0.8
(0.3-1.7)
0.9
(0.4-2.1)
High
37
(28.2)
92
(24.3)
1.4
(0.7-3.0)
1.3
(0.6-2.9)
Highest
36
(27.5)
90
(23.7)
1.4
(0.7-2.9)
0.9
(0.4-2.1)
adjusted
adjusted
CI)
fruits
Lowest
0.98
0.17
P for trend
,, OR1
CI)
(%)
for lifetime
consumption
for the same variables
of alcohol.
cigarette
smoking,
and the design
variables
age group,
as for OR1 plus consumption
of red meats,
fats, fish, and milk. For
who reported
drinking
mate
at very hot temperatures
had a
2-fold increase
in risk as compared
to those drinking
it warm or
hot. This association
was particularly
strong for those drinking
mate
e’ocido
very hot with a 6-fold increase
in risk as compared
to those drinking
it warm or hot.
Our findings
are in agreement
with earlier
experimental
work
in human
volunteers
showing
that after ingesting
hot
liquids,
the intra-esophageal
temperature
depends
more on
the volume
swallowed
at each sip than on the temperature
of
the liquid (I 1). It is likely
that those drinking
hot mate
from
a cup or jar had a tendency
to swallow
greater
volumes
than
did those
drinking
hot mate
from a gourd
through
a metal
straw.
The results
from
this study
support
the evidence
that
chronic
thermal
injury
plays
a role in esophageal
carcinogenesis.
In South
America,
the Brazilian
study
found
no
association
with mate
temperature,
although
it did detect
a
nonsignificant
association
with frequency
of mate
drinking
( 4); in Uruguay,
a large
dose-response
relationship
was
found
with amount
and, to a lesser
extent,
with duration
of
hot mate
drinking,
although
the effect
of temperature
was
inconsistent
(5); in Argentina,
a small and marginal
effect of
hot mate
temperature
consumption
was found
(OR = 1.7;
95%
CI = 1.0-2.9;
Ref. 7). Table
6 summarizes
the effects
of these
and other
selected
variables
on esophageal
cancer
risk in the four case-control
studies
coordinated
by IARC
in
South
America.
Studies
in other
populations
have also found
a significant effect
of hot drinking
on esophageal
cancer
and its
precancerous
lesions.
A study
among
young
adults
in a
high-risk
area of China
revealed
that the habit of drinking
“burning
hot” beverages
was the strongest
risk factor
for
esophagitis
(12).
In a case-control
study
in Hong
Kong,
preference
for consuming
drinks
or soups
at high temperatures was associated
with esophageal
cancer
risk accounting
for 14% of this cancer
in this population
(13). In a recent
case-control
study in Northeast
China,
scalding
temperature
of meals
and drinks
was identified
as the strongest
dietary
risk factor
for esophageal
cancer
(14). Ingestion
of drinks
at
high temperature
has also been shown
to increase
the risk of
this cancer
in earlier
studies
in Puerto
Rico (15), Singapore
(16), and Iran (17).
The measurement
of the temperature
at which drinks were
consumed
was subject
to misclassification
in this study because
it was self- reported
and, therefore,
subjective.
However,
as the
association
between
hot temperature
and esophageal
cancer risk
was practically
unknown
in the study population,
there is no
reason
to think that misclassification
was differential
with regard to case-control
status,
which
is the type of misclassification that could spuriously
overestimate
an association.
If mis-
sex,
beef,
and hospital
group.
the model
was not adjusted
for red
meat.
classification
existed
it is likely that it was nondifferential
(that
is, cases and controls
were equally
likely to misclassify
temperature
status and in the same direction),
and the reported
risk
estimates
might
be, in fact, an underestimation
of the real
underlying
effect of temperature.
A substantial
underestimation
of the temperature
effect
has in fact been suggested
by a
validation
study conducted
in Brazil and Uruguay.3
Further,
as
shown
in a study conducted
in Iran, when tea temperature
is
actually
measured,
avoiding
thus the bias potentially
introduced
by self-reporting
measurements,
a convincing
association
between measured
tea temperature
and population
risk of esophageal cancer
is also found (18).
Concerning
amount
and duration
of hot mate
drinking,
our observations
are at variance
with the results
from similar
studies
in Uruguay
in which
strong
dose-response
relationships
have
been
reported
between
daily
amount
of mate
consumed
and cancers
of the esophagus
(3, 5, 6), oropharynx
(19), and larynx
(20). In this context,
it is interesting
to note
that the mean daily
amount
of hot mate
drunk
among
controls in Paraguay
(872.2
ml) is similar
to the mean
amount
consumed
in Uruguay
(950.5
ml). On the other
hand,
the
results
of the Paraguay
study
are in line with those reported
in Brazil
on esophageal(4)
and oral cancer
(21) and with the
results
of studies
in Argentina
on esophageal
(7) and bladder
cancer
(22) (Table
6).
The unexpected
finding
of a statistically
significant
inverse
trend with years,of
consumption
of hot mate drinking
is puzzling
and difficult
to explain
as it even persisted
after
adjusting
for amount
and temperature
of hot mate consumption. One could speculate,
however,
that duration
of a widespread
habit,
as mate
drinking
is in this population,
may be
subject
to differential
misclassification
of the exposure
and
perhaps
to recall
bias. This possibility
could
not be further
assessed
with the data collected.
Alternatively,
the protective
effect observed
with duration
might be partially
explained
by
the possibility
that early
symptoms
of esophageal
disease
might
have encouraged
cases
more frequently
than controls
to stop the habit.
This would
be consistent
with the observation
that current
hot mate drinkers
were
at a lower
risk
than past hot mate
drinkers,
although
the latter were only a
few (Table
2).
As shown
in Table 6, the effect of duration
of hot mate
drinking
was not significant
in Brazil
and Argentina
but, contrary to the observed
in this study, it was positively
associated
with risk in Uruguay.
3
C. G. Victora,
personal
communication.
Downloaded from cebp.aacrjournals.org on October 30, 2016. © 1995 American Association for Cancer Research.
Cancer
Table
6
Effects
o f selected
variables
on esophage
Uruguay
(5)
al cancer
risk
in four
Brazil
(4)
e ase-control
studies
Epidemiology,
from
South
Biomarkers
& Prevention
America
Study
Variables
Study period
No.
of cases/No.
Male
Argentina
(7)
Paraguay
1985-1988
1985-1986
1986-1989
1988-1991
261/522
171/342
131/262
131/381
of controls
drinking
Amount
ns
ns
Duration
+
ns
ns
Temperature
+
ns
+
+
Cigarette
+“
ns
ns
+
+
smoking
Amount
++
Duration
+
+
+
+
+
+
+
+
+
n/a
+
+
+
Type
of tobacco
++
++
(black)
Alcohol
(black)
(black)
++
++
drinking
Amount
++
Duration
Type
++
++
+
of alcohol
wine
++
and spirit
+
+
wine
cacha#{231}a5
aquardienle5
Diet
Meat
ns’
Barbecue
++
Fats
+
ns
Vegetables
Fruits
ns, not significant;
--
n/a, data
not available;
effect.
I, Cae/ta#{231}a and
aguardieFile
are distilled
( Consumption
of any fresh meat.
(I Consumption
of beef.
,. Consumption
of beef or any red meat.
I No distinction
was made between
raw
C For
daily consumption
of lemons.
+ ,
significant
harmful
+
+(#{149}
n/a
ns
ns
ns
“
+
+ .
strongly
significant
+
harmful
effect;
-, significant
+
ns
ns
--
effect;
+
ns
++
-
protective
effect;
-
- , strongly
significant
protective
sugar
and
cane
cooked
spirits.
vegetables.
Cigarette
Smoking
and Type of Tobacco.
In agreement
with
most
published
case-control
studies,
we found
a strong,
dose-effect
association
with amount
and duration
of smoking, and, inversely,
with time since stopping
the habit. Blond
tobacco
smoking
is associated
with a 50% reduction
in risk
as compared
to black
tobacco
smoking.
The fact that the
adjusted
and crude risk estimates
for blond tobacco
smoking
were of the same magnitude
suggests
a real effect
of type of
tobacco
and that the study
probably
did not have sufficient
statistical
power
to detect
such
effect
in the multivariate
analysis.
Further,
the analysis
of the average
number
of
blond cigarettes
smoked/day
did not show a significant
positive effect
(for those smoking
>20 blond
cigarettes/day
as
compared
to nonsmokers:
OR = 1.3 and 95% CI
0.5-3.4).
These
findings
are reinforced
by those
from
other
casecontrol
studies
on esophageal
cancer
in Uruguay
(5)
and
Argentina
(7) (Table
6), on oropharyngeal
cancer
in Uruguay
(19), on bladder
cancer
in Italy (23) and Argentina
(22), as
well as by laboratory
studies
showing
that black
tobacco
is
more carcinogenic
than blond
tobacco
in terms
of tobaccospecific
nitrosamines
and aromatic
amines
(24) and mutagenie
activity
(25).
Alcohol
Consumption
and Type of Beverage.
As expected
and consistent
with the other South America
studies
(Table
6),
alcohol
drinking
was the strongest
risk factor
for esophageal
cancer
in this population.
All measures
of alcohol
exposure
were strongly
associated
with esophageal
cancer
risk with a
strong dose-response
relationship
with daily and lifetime
average amounts
of pure ethanol
consumed
and, marginally,
with
the time elapsed
since stopping
the habit. Although
there was a
strong association
with duration,
the trend was not evident.
This
lack of a dose-response
relationship
between
duration
and risk
has also been reported
in the studies
from Uruguay
(5)
and
Argentina
(7). It is worth
noting
that the increased
risk found
with alcohol
drinking
was mainly
related
to the consumption
of
spirits
or aguardiente,
the most prevalent
type of alcoholic
beverage
in this population
(77% in cases and 27% in controls).
No significant
associations
were detected
with beer (jrevalence: 21% in cases and 15% in controls)
or with wine (preyalence:
24% in cases and 12% in controls).
These
prevalences
are in contrast
to those
from
Uruguay
in which
the most
prevalent
alcohol’ beverage
was wine, followed
by spirits
and
beer (5).
Although
there is no doubt that alcohol
and smoking
are
strongly
associated
with esophageal
cancer
risk, we should
be
aware that the magnitude
of these effects
might be somewhat
overestimated
in this study because
by design
patients
with
smoking
or alcohol-related
diagnoses
were excluded
from the
control
population.
Dietary
Food
Groups.
The positive
effect
of red meats
found
in this study is in line with that found
in the Brazilian
study but not with that of the Argentinean
study in which
a
significant
protective
effect
was found,
nor with
that of
Uruguay
in which
the protective
effect was not evident
after
adjustment
was made for the consumption
of barbecued
meat
(Table
6). Recently,
a study
using ecological
data from 59
countries,
also found
a highly
significant
association
between
high meat animal
product
consumption
and esophageal cancer
mortality
rates (26).
Meat intake
has also been
found
to be positively
associated
with stomach
cancer
(27)
and other cancers
of the upper
digestive
tract (28). In contrast,
a large
case-control
study
conducted
in Calvados,
France,
found a protective
effect
for fresh meat consumption
(29).
Downloaded from cebp.aacrjournals.org on October 30, 2016. © 1995 American Association for Cancer Research.
603
604
Male
Drinking
and
Esophageal
Cancer
in Paraguay
As with the Argentinean
study,
the protective
associalions
found
for consumption
of fruits and vegetables
when
assessed
as food groups
were very weak and statistically
not
significant.
This finding
is unusual
because
clear protective
associations
with high consumption
of fruits and vegetables
have been identified
in the studies
of Brazil
and Uruguay
(Table
6), as well as in most
other
studies
of esophageal
cancer
in Western
countries
and among
Chinese
(14,
16,
29-32).
Only
another
case-control
study
of cancer
of the
esophagus
and gastric
cardia
conducted
in Linxian,
China,
failed
to find a lower
risk among
persons
consuming
more
fresh vegetables
and fruits (33, 34). However,
our data is not
that inconsistent
because
when
assessing
the effect
of specific fruit items, we did find a significant
protective
effect of
daily consumption
of lemons
and a nonsignificant
protective
effect
of daily consumption
of oranges.
The protective
effect
of cereals,
cereal
products,
and
cheese
observed
in this study may reflect
a better
nutritional
status that has been related
to a decreased
risk for esophageal
cancer
in other
studies
(31).
Another
study
of oral
and
pharyngeal
cancer
reports
also an inverse
association
with
increasing
bread
and cereal
consumption,
which
was independent
of the effect
of other
food groups
including
fruits
and vegetables
(28).
In interpreting
these
dietary
findings,
we should
be aware
of the limitations
existing
in epidemiological
studies
investigating
the effect of food consumption
on cancer
through
dietary
questionnaires.
Moreover,
the
dietary
results
of this study are based on a rather simple
food
frequency
questionnaire
that was answered
by ill subjects
who
often
had limited
education
or a history
of heavy
drinking.
Thus,
the dietary
associations
identified
in this
study should
be interpreted
cautiously.
Possible
additional
limitations
of the present
study
are
selection
and recall bias. Concerning
cases,
selection
bias is
unlikely
to be of importance
because
it is estimated
that
about 80% of the cases occurring
and fulfilling
the inclusion
criteria
in AsunciOn
were
recruited
for the study.
For
controls
we tried to reduce
the selection
bias by selecting
them from several
diagnostic
categories,
and only 12 control
subjects
(3.1%)
refused
to participate.
Recall
bias is unlikely
to have
generated
differences
between
cases
and controls
concerning
alcohol,
tobacco,
and reported
temperature
at
which
mate
is drunk
because
their
associations
with
esophageal
cancer
are mostly
unknown
to the general
population.
In conclusion,
the findings
from this study suggest
that
the temperature
at which
mate
is drunk,
but not the amount
or the duration,
is an important
risk factor
for esophageal
cancer
in this population
and that cold mate
drinking
does
not increase
esophageal
cancer
risk. Consistent
with other
studies
in South America
and elsewhere,
this study identifies
alcohol
drinking
and tobacco
smoking
as the main
risk
factors
for esophageal
cancer
in Paraguay.
High consumption of red meats
and fats are the main dietary
risk factors
identified
in this population.
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