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Diet and the risk of vulvar cancer
Diet and the Risk of Vulvar Cancer Susan R. Sturgeon, MPH, Regina G. Ziegler, PhD, Louise A. Brinton, PhD, Philip C. Nasca, PhD, Katherine Mallin, PhD, and Gloria Gridley, MS In this case-control study, 201 cuse patients with wulvar cuncer and 342 community control subjects responded to a 6 I -item food frequency questionnaire. Risk was unrelated to intake of dark green vegetables, citrus fruits, legumes, and vitamins A and C and folate. Risk increased modestly with decreased intake of dark yellow-orange vegetables; the relative risk for the lowest versus the highest quartile was 1.6. Analyses using preliminary determinations of the major carotenoids in common fruits and vegetables suggested that alpha carotene might be the protective constituent in dark yellow-orange vegetables. Intake betacurotene and provitumin A carotenoids was unrelated to risk. Multiwitamm users were at lower risk, compared to nonusers, but no trend wus observed with increasing years of use, suggesting that this association was due to unmeasured differences in lifestyle factors. Risk mcreused irregularly with the number of cups of coffee consumed per week whereas consumption of alcohol was unrelated to risk. Ann Epidemiol 1991; I :427-437.
of
KEY WORDS:
Vulvar cuncer, diet, carotenoids,
alpha carotene
INTRODUCTION Carcinoma
of the vulva
incidence
rate for invasive
vulvar
women/y
(1). Risk factors
associated
for cervical
cancer
of genital
warts,
and include
cervical
cancer
status
multiple
squamous-cell
and vulvar
cancer
have
sexual
the average
(3).
cancer
annual
cigarette
on Papanicolaou
evidence
2/100,000
to those
reported
smoking, smear
associated
frequent
age-adjusted
is less than
are similar
consistently
The
further
States
partners,
tinding
also been
tumors provides
tumor;
in the United
with vulvar
and a prior abnormal
of low socioeconomic predominantly
is a rare gynecologic
(2). Indicators with
simultaneous
for a possible
a history these
two
occurrence
of
common
etiology
(4). Recent might
attention
explain
that persists found
dietary
enoids
(58),
has focused
the association after adjustment intake
of dark green or orange
dysplasia
and vitamin
or neoplasia
than
vegetables C (6,9-l
among
with folic acid has been associated users of oral contraceptives
We evaluated
the relation
between
from a large case-control
the etiology
of cervical
cancer
study,
status
dietary
deficiencies
and cervical
risk factors.
Some
(5, 6), vitamin
cancer studies
A (7), carot-
1) to be lower among
comparison
dysplasia obtained
certain
and other
supplementation among
that
low socioeconomic
for sexual behavior
fruit juices (6,9),
with cervical
on the possibility
between
individuals.
individuals In addition,
with an improvement
in cervical
( 12). diet and vulvar to determine
also influence
cancer if dietary
using interview factors
the risk of vulvar cancer.
implicated In addition,
data in we
428
AEP Vol. 1, No. 5 August 1991: 427-437
Sturgeon et al. DIET AND THE RISK OF VULVAR CANCER
examined the roles of coffee and alcohol and vulvar lated as risk factors for vulvar cancer in a case-control
cancer because these were postustudy by Mabuchi and colleagues
(13).
METHODS Details
on the selection
are presented confirmed
elsewhere vulvar
participating subjects
of case patients
hospitals
diagnosed
for age (i-year Care
interviews
were obtained
Reasons
for nonresponse
control
subjects),
addition,
moved
or inability
having
3%),
exchange
for controls
under
rosters
for those
(61%)
and 348 control
to locate
and other
it was not possible
subjects
versus 34% of
(4% versus 9%),
problems
(2% versus
to obtain
the
65 and older.
death
3%).
physician
In
consent
an interview.
A structured mation
refusal
(6% versus
(telephone
techniques
at 34
of 686 control
( 18% of case patients
included
illness
identified
A total
race, and residence
digit dialing
study methods
and pathologically
1987 were
York.
from 209 case patients
for 6% of the case patients
to conduct
New
Administration
subject
and other
with incident
1985 and
upstate
age groups),
Financing
(51%).
1%))
and
using random
Home
(3% versus
between
in Chicago
or zip code) were selected age of 65 or Health
subjects,
(2). Briefly, 344 case patients
cancer
matched
and control
interview
on hypothesized
was administered
risk factors,
by trained
including
interviewers,
demographics,
to obtain
infor-
history,
men-
pregnancy
cigarette smoking, sexual and contraceptive strual history and hygiene practices, behavior, medical events, and diet. Diet was assessed using a food frequency questionnaire that included folate
the major food sources
in the diets of whites,
each
of 61 food
changes”
items,
subjects
to be consumed
data collected
in the
Food Consumption or “don’t
know”
analyses.
Survey responses
(16).
“usual
an approximate
Fourteen
A, carotenoids, in the United adult
per day, week,
US Department
intake, month,
season (8 cases,
subjects
included
on 99% of the food items of interest.
The
15). For
ignoring
recent
was assigned
(USDA) 6 controls)
in the study,
C, and
(14,
or year. For foods
length
of Agriculture
subjects
vitamin
States
with missing from the
complete
mean
from
Nationwide
for five or more of the food items were excluded
For the remaining
tion was available
their
of servings
seasonally,
1977-78
of vitamin
and Hispanics
provided
in terms of the number
reported
dietary
blacks,
informa-
ages of the tinal
dataset of 201 case patients and 342 controls were 53.9 and 52.6 years, respectively. Non-Hispanic whites comprised 86.5% of the case patients and 85.6% of the controls. Analyses and nutrient frequencies intake
of the dietary intake.
of consumption
was calculated
food items containing
data were conducted
Food group
intake
of the food
as the weighted the nutrient;
using measures
was calculated items
incuded
servings of the food. Portion size, food preparation practices, of a food item were estimated using methods
food group
in the food group.
sum of the frequencies
weights
of both
as the sum of the reported of consumption
used were the nutrient
contents
Nutrient of the of typical
and nutrient content of a typical serving described by Ziegler and associates ( 17).
Estimates obtained
of portion size and preparation practices were hased on 24-hour dietary recalls on a representative sample of the US population (Second National Health values and Nutrition Examination Survey (NHANES II)) (15). Th e f00 d composition assigned were an updated version of the values used in NHANES 11 (18). Estimates of
vitamin A and carotenoids beta carotene has one-sixth (19).
Folate
content
were updated according to the current convention that the vitamin A activity of an equivalent intake of retinal tables was obtained from the 1978-88 USDA foo d composition
Sturgeon et al. DIET AND THE RISK OF VULVAR CANCER
AEP Vol. 1, No. 5 August 1991: 427-437
(20) with updated (21).
Estimates
information
from recent
of five major
carotenoids
vegetables were obtained ments from the USDA and nutrient
intakes
laboratory
and proprietary
in approximately
from published reports (Beecher GR, personal
were treated
research
as categorical
sources
30 common
(22) and recent communication, exposure
429
fruits
and
preliminary measure1990). Food group
variables;
each measure
was
stratified into quartiles based on the frequency distribution in the control group. Subjects were also asked whether they had used supplemental vitamins on a regular basis and, subjects
if so, for how many years. For the measurement were queried
individual
supplements
In addition,
respectively and vulvar
and intensity
RRs of the
Weekly
and hard liquor yields
ethanol
of
intake
was
1.1, 2.9, and 9.4 g of
were 8, 4, and 1 fl oz, respectively
adjustment
techniques
partners,
indices
exsmoker,
(23).
intervals
A caffeine
history
any of the estimates.
as continuous
in a regression
using
explored
herpes
in-
or warts,
result on Papanicolaou New only
York,
Chicago).
for age,
of sexual partners, exposure
cigarette
since further
Tests for linear
a score to each level of a categorical
the variable
Adjusted
of genital
adjusted
and number
exposures
confounders
abnormal
were
dietary
risk (RR).
(CI) were derived
Potential
a previous
presented
change
between
of relative
and study area (upstate
nonsmoker),
did not materially by assigning
smoking,
age, race,
dietary
(25).
a self-reported
of cigarette
various
of association
as an estimate
and 95% confidence
regression
education,
(current,
treating
per day,
a cupful of tea and coffee yields 60 and 90 mg of caffeine,
estimates
of sexual
income,
obtained
wine,
taken.
on usual adult consumption
and tea was also obtained.
was the odds ratio,
logistic
number
smoking
usual adult
Information
used to assess the strength
likelihood
unconditional
smear,
consumption
assuming
cancer
maximum
duration
typically
and spirits.
intake,
(24).
The measure
cluded
of multivitamins their
usual servings
index was estimated
vitamin
brand
1 fl oz of beer,
and that
of specific
A, C, and E and folic acid as
about
coffee,
assuming
ethanol,
use of vitamins
were asked
of beer, wine,
decaffeinated
estimated
their
and the name
subjects
week, or month coffee,
regarding
variable
trend
were
and then
model.
RESULTS
Food Groups and Micronutrients Table
1 presents
the RRs of vulvar cancer
of dark yellow-orange
vegetables
was related
cancer,
to vulvar
lowest quartiles of dark green
of intake. vegetables,
legumes,
including
of citrus
and juices
such
as broccoli,
was also unrelated
vegetables,
fruits and juices,
risk of vulvar cancer complex
Table 2 presents risk estimates supplements. There were no trends C, vitamin
A, carotenoids,
with food groups. pumpkin, elevated
in risk were observed
green and black-eyed
between
carrots,
with risk estimates
No trends
association
associated
including
spinach,
among
women
with decreasing
turnip
peas and green,
Reduced
sweet potatoes,
greens,
in the two consumption
and collards,
lima, and pinto beans.
to risk. Furthermore,
there
meat,
or
Intake
was no consistent
and intake of the basic food groups, carbohydrates,
intake
and yams
including
and dairy products.
for micronutrients, excluding intake from vitamin in risk associated with decreasing intake of vitamin
or folate.
Individual Carotenoids In Table
3, vulvar
cancer
risk is presented
in relation
to estimated
dietary
intake
of
individual carotenoids, including alpha carotene, beta carotene, lutein, lycopene, and cryptoxanthin. The RRs for women in each the three lowest quartiles of alpha carotene intake were elevated. Intake of the other individual carotenoids was unrelated to risk.
430
Sturgeon et al. DIET AND THE RISK OF VULVAR CANCER
TABLE 1 food groups
Relative
mks
Food group (servings/w)
Dark yellow-orange vegerahles Ql 2 2.6 Q2 1.5-2.5 Q3 .7-1.4 (24 5 .6Y
Al? Vul. I, No. 5 August 1991 427-437
(RRs) of vulvar
cancer
associated
Cases (n = 201)
with
Controls (n = 342)
38 6L1 66
86 86 87 ni
Q4 5 2.4
60 45 51 45
Legumes Ql 2 5.7 Q2 3.7-5.6 43 2.3-3.6 44 5 2.2
37
intake
of selected
Adjusted RRs” (95”/0 CI)
1.00
.Y3 1.4’) 1.59 I’tru
(.5%1.6) (.Y-2.6) (.Y-2.7) trend = .O3
88 Yl 78 85
1.00 .71 1.04 .il 1’for
(.4-1.2) (.6-1.7) (.4-1.2) trend = .41
60 43 58 40
87 84 86 85
1.00 .80 1.11 .70 P for
(.5-1.1) (.7-1.8) (.4-1.2) trend = .40
Citrus fruits and Juices Ql 2 10.3 42 7.1-10.2 43 3.2-7.0 Q4 5 3.1
49 50 39 63
85 86 86 85
1.00 1.11 .78 1.20 I’ior
(.7&1.Y) (.5-1.4) (.iP2.0) trend = .73
Vegetables Ql 2 21.5 Q2 16.3-21.4 Q3 11.8-16.2 44 5 11.7
56 38 45 62
8i 84 87 84
1.00 .76 .76 l.OY I’for
(.i-1.3) (.5-1.3) (.7-1.8) trend = .72
Fruts Ql Q2 43 44
and jutes 2 20.9 13.9-20.8 9.0-13.8 5 8.9
56 44 34 67
86 85 87 84
1.00 .7Y .54 1.01 P fur
(.5-1.3) (.3-.Y) (.6-1.7) trend = .76
Complex carbohydrates Ql 2 18.1 Q2 13.4-18.0 43 10.4-13.3 Q4 5 10.3
61 55 41 44
86 86 86 84
1.00 .Y6 .70 .77 P for
(.6-1.6) (.4-1.2) (.5-1.3) trend = .19
Meat Ql Q2 Q3 Q4
58
46 51 46
86 86 85 85
1.00 .86 .Y7 .70 P for
(.5-1.4) (.6-1.6) (.4-1.2) trend = .27
46 53 54 48
86 86 a7 83
1.00 1.06 1.15 1.00 I’for
(.6-1.8) (.7-1.9) (.6-1.7) trend = .Y3
Dark green vegetables (21 2 6.0 (22 4.3-5.9 43 2.5-3.9
2 13.0 9.4-12.9 7.0-9.3 5 6.9
Dairy products Ql 2 16.4 Q2 11.1-16.3 Q3 6.5-11.0 Q4 5 6.4
’ Adjusted for age, number of sexual partners, and cigarette smokmg.
AEP Vol.
Sturgeon et al. DIET AND THE RISK OF VULVAR CANCER
I, Ntr. 5
August 1991. 427-437
TABLE
2
Relative
risks (RRs)
of vulvar
431
cancer associated with estimated intake of
selected micronutrients Micronutrient
Cases (n = 201)
Controls (n = 342)
Adjusted RR+ (95% CI)
Vltanm c (mgid) Ql 2 203 Q2 153-202 Q3 112-152 Q4 5 111
55 42 37 67
85 86 86 85
1.00 .86 (.5-1.4) .71 (.4-1.2) 1.15 (.7-1.9) P tar trend = .72
bl 43 40 57
85 86 86 85
1.00 .71 .67 .93 1 for
A (REld) QI 5 1465 Q,! 1067-1464 Q, 779-1066
Vitanun
Q4 5 778 Carotenolds (RE/d)h Ql 2 736 Q.2 521-735 Q, 369-520 Q4 5 368 Folare &id) Ql 2 299 Q2 233-298 Q1 180-232 Q4 5 179
(.4-1.2) (.4-1.1) (.6-1.5) trend =
.71
53 37 41 70
85 86 86 85
1.00 .73 (.4-1.3) .69 (.4-1.2) 1.20 (.7-2.0) I’ for trend = .47
54
85 86 86 85
1.00 .93 .68 1.02 P for
50 39 58
(.6-1.6) (.4-1.2) (.6-1.7) trend = .77
A strong correlation was observed between intake of dark yellow-orange vegetables and alpha carotene because dark yellow-orange vegetables are the major source of alpha carotene (Spearman’sr = .79, P = .OOOl). A s sh own in Table 4, it was not possible to assess the independent effects of these two dietary exposures on risk because so few women had discordant intake levels of dark yellow-orange vegetables and alpha carotene.
Supplemental Vitamins Table 5 shows the RRs associated with years of supplemental vitamin use. Combining intake from individual vitamins and multivitamins, risk was substantially lower among users of vitamins C, A, and E and folic acid. Multivitamin users were also at lower risk than were nonusers. Limiting comparisons to within vitamin takers only, however, no reductions in risk were observed with increasing years of use of vitamin A or multivitamins. Only modest decreasing trends in risk were noted with increasing years of use of vitamins C and E and folic acid. To estimate the combined effect of diet and vitamin intake, we examined the risks associated with years of supplemental vitamin intake of vitamins A and C and folic acid among women at each level of dietary intake of these nutrients. The effect of dietary intake of vitamins A and C and folate was also examined separately among users and nonusers of the respective supplemental vitamin (data not shown). Similar protective effects for supplemental vitamins A and C and folic acid as shown in Table
432
Sturgeon et al. DIET AND THE RISK OF WLVAR CANCER
AEP Vol. I, No. 5 Augwt 1991: 427-437
TABLE 3 Relative risks (RRs) of vulvar cancer associated with estimated individual carotenoids
intake of
Carotenoid
Cases (n = 201)
Controls (n = 342)
Alpha carotene (/q/d) (21 2 569 Q2 350-568 43 207-349 Q4 2 206
32 55 52 62
85 86 86 85
Beta carotene (pgld) (21 2 3006 (22 2048-3005 Q3 1284-2047 Q4 5 1283
44 41 54 62
85 86 86 85
Lutein &Id) Ql 2 4571 Q2 2784-4570 Q3 1279-2783 Q4 c 1278
54 54 42 51
85 86 86 85
1.00 1.02 (.6-1.7) .87 (.5-1.5) .98 (.6-1.6) P for trend = .81
Lycopene (pgld) (11 2 368 (12 259-367 Q3 170-258 (24 5 169
53 46 57 45
84 87 86 85
1.00
Cryptoxanthin @g/d) Ql 2 289 Q2 186-288 Q3 126-185 Q4 5 125
49 43 50 59
85 86 86 85
Adjusted RRs (95% CI)
1.00
1.60 1.56 1.74 P for
(.9-2.8) (.9-2.7) (1.0-3.0) trend = .09
1.00
.88 (.5-1.5) 1.23 (.7-2.1) 1.26 (.7-2.1) P for trend = .23
.81 (.5-1.4) 1.23 (.7-2.1) .79 (.5-1.3) P for trend = .76 1.00
.79 (.5-1.3) .94 (.6-1.6) .97 (.6-1.6) P for trend = .36
a Adjustedfor age, cigarettesmoking,and numberof sexualpartners
among women in each quartile of dietary intake of vitamins A and C and folate. On the other hand, no relationship between risk and dietary intake of vitamins A or C or folate was observed among either users or nonusers of the respective supplement. Closer evaluation of the effects of specific vitamins was limited because most women reported using multivitamins containing vitamins A, C, and E and folate, or individual supplements in combination with multivitamins. Among the 253 women taking vitamins C, E, or A or folic acid, 62% were taking all four, 14% were taking a combination of three, and 9% were taking a combination of two. Among women taking only one vitamin, 24 were taking vitamin C, six were taking vitamin E, and two were taking folic acid; no women reported taking only vitamin A.
5 were evident
Coffee and Alcohol
Consumption
The relationship of risk to consumption of caffeinated and decaffeinated hot beverages is shown in Table 6. Although risk was modestly elevated among women consuming more than three cups of coffee per day even after adjustment for age, sexual behavior, and cigarette smoking (RR = 1.72; CI, 1.0 to 3.0), the pattern of increasing risk with
433
sturgeon et al. DIET AND THE RISK OF VULVAR CANCER
AEP Vol. I, No. 5 August 1991: 427-433
TABLE 4 Relative risks” of vulvar cancer associated with level of intake of alpha camtene and dark yellow-orange vegetables Quartile Quartile of dark yellow-orange vegetable intake
(24 (Low) for age,
’ In parentheses
’Referent
cigarette
smoking,
are numbers
of cahe
and
Q4
.8@ (1,2) .96 (1@,22) 1.52 (X43) 1.42 (13,19)
.9i
1.00
Q3
(23
(Low)
(9.20) 1.08 (22,45) 2.18 (18,li) 2.69 (6.4)
(26,63) .51 (4.15) .39 (1,4) .6i (1.3)
Q2
intakeh
Q2
(I-&h)
Ql Wish)
’-4djusted
of
alpha carotene
number
pat~enrs
and
of cexu~l control
3.70 (1.1) l.Oi (2,4) 1.18 (13,23) 1.61 (46,57)
pxtncra.
suh]rcr~
category.
increasing
coffee
wasalso
consumption
was irregular.
Among
nonsmokers,
the pattern
(RR = 1.0, 1.75, 1.47, 1.37, 1.79). C onsumption
irregular
coffee and tea was unrelated
to risk. The caffeine
index
of risk
of decaffeinated
also showed
no clear relation
with risk. There
was no association
risk of vulvar including
cancer
beer,
with increasing
(data
wine,
between not
and spirits
intake
the overall
shown).
When
amount
were examined,
after adjustment
types
risk was not appreciably
increased
for age, sexual behavior,
between Dietary Risk Factors if the dietary
confounded
intake,
supplemental
regression There
by each
model
vitamin
along
with
was no evidence
and cigarette
factors found to be associated
other,
dark
yellow-orange
of confounding
smoking,
or alpha
were entered
and number
as the risk estimates
smoking.
with risk in this study
vegetable
use, and coffee consumption age, cigarette
and
beverages
Finally, were
consumed
of alcohol
Interrelationship to determine
of ethanol
specific
of sexual
presented
carotene
together
into a
partners.
earlier
in the
text were unchanged.
TABLE
5
Relati\ze risks” of vulvar cancer associated with years of supplemental Years
Type of vitamin
Vitamin C Vltamm A Vwmm E Fohc acd Multivitamins
0
1.0 (123,162) 1.0 (135,193) 1.0 (123,180) 1.0 (141.208) 1.0 (135,186)
l-3 .65 (16,33) .66 (12,25) .86 (17,28) .74 (12.23) .58 (11326)
4-9
.68 (22,4L1) .i!
(15,28! .85 (21935) .79 (li,Jii .i9
(13,30)
vitamin use
taken”
10-15 .iS
(13,32) .44 (8,26) .50 (9.26) ,517 (7,221 .41 (11,38)
16+ .47 (22.65) .i6 (X.53) .ii (22.611)
P for trend cm6
,177 .09
.i9
.I1
(l&44) .i9 (li,41)
.08
Unknown .ii
(5.10) 1.1: (Il,li) 1.23 (9.13) 1.X (10,181 1.Z (14.21)
434
AEP Vol. 1, No. 5 Augwt 1991: 427-437
Sturgeon et al. DIET AND THE RISK OF VULVAR CANCER
TABLE 6 Relative risks (RRs)” of vulvar cancer associated with intake of caffeinated decaffeinated beverages Beverage
Cases
Unadjusted RRs
Controls
and
Adjusted RRs (95% CI)
coffee(cups/d) 0
105 99 48 41 49
48 51 35 LO 47
3 4+ Decaffeinated coffee (cups/d) 0 Ii
I.00
1.00 i.lY (.7-2.0) 1.59 (.Y-2.9) 1.03 (.5-2.0) 1.72 (1.0-3.0) P for trend = .OY
1.13 1.60 l.t?i 2.09
134 48 19
202 104 36
1.00
56
69 221 30 22
1.00
114 17 14
13 34 47 49 58
24 79 80 82 77
1.00
1.00 .77 (.5-1.2) .89 (.i-1.7) I’ for trend = .40
.io .80
Tea (cups/d) 0 2 3+ Caffeme Index (mgid) 0 1-63 64-154 155-271 272i
1.00 .66 (.4-1.0) .77 (.4-1.6) 1.172 (.4-2.3) P for trend = .71
.64 .iG .78
1.02 .i6 (.3-1.7) 1.11 (.5-2.5) 1.13 (.5-2.5) 1.21 (.i-2.7) P hr trend =
.80
1.09 1.10 1.39
(18
DISCUSSION Among
the various
food groups,
cancer.
An increased
and Individual
micronutrients,
in this study, only twc> closely correlated
dietary
risk of vulvar cancer
exposures
was observed
carotenoids
were associated
among
wOrnen with decreased
intake of dark yellow-orange vegetables or alpha carotene. However, separate an alpha carotene effect from the effect of dark yellow-orange se because study,
the rncjst common
carrota,
is rich
in alpha
dark yellow-orange carotene
vegetable
and there
are only
eaten
we found no beta carotene
A carotenoids therefore
effect using either
or with beta carotene
inconsistent
measured
with the findings
USDA
directly.
of protective
The
we could vegetables
by women
a few sources
carc>tene other than dark yellow-orange vegetahles (e.g., peaches, Dark yellow-orange vegetables are also a rich dietary source however,
examined with vulvar
corn). of beta
estimates results
not per
in this of alpha
carotene;
of provitamin
of this study are
effects of beta carotene
that have
been reported in several studies of cervical cancer (5-8). On the other hand, our results are in agreement with a large study of in situ cervical cancer in which provitamin A carotenoids were not associated with risk hut dark yellow-orange vegetable intake did appear tc>exert some protective effect (26). Furthermore, Murakoshi and colleagues (27) reported that alpha carotene has nearly ten times the antiproliferative activity of beta carotene plausibility
on a human of our finding
retinoblastoma an effect
cell line, providing
for alpha
carotene
evidence
for the biologic
but not for beta carotene.
435
Sturgeon et al. DIET AND THE RISK OF VULVAR CANCER
AEP Vol. I, No. 5 August 1991: 427-437
A relationship (4, 5), though
of dietary
risk of vulvar
cancer.
fruits and juices,
C with cervical
Intake
that
of vitamic
dark green vegetables)
subjects. The rationale
for suspecting
from a small clinical regressed
vitamin
our data do not indicate
consistent
cancer
risk has been
vitamic
C intake
suggested
increases
the
C or foods rich in this compound
(i.e.,
was similar
and control
between
case patients
that folate might affect risk of vulvar cancer
trial in which
cervical
on folic acid administration
risk is, however,
reduced
dysplasia
citrus
is derived
in users of oral contraceptives
(12). The lack of a folate effect on vulvar cancer
with several
case-control
studies
of cervical
cancer
(9, 17,
26). If individuals intake,
in this study were seriously
underlying
obscured. quency
true associations
Although
potential
questionnaires
problems
results
when
in time,
and to correlate
caution
should
because
laboratory
and vegetables. foods, vitamins examine
seasons,
and cooking
a protective
examined
in this study.
Taking
protective of these
however,
appeared
with vulvar cancer choose
invastve women
taking
in this
suggest
vitamins
cancer,
and
Ziegler
supplemental
An earlier
vitamins
intake
was modest
of coffee
colleagues
(13)
of vitamins
who
A and C and folacin, of these
respective
of supplemental
do not.
factors
Obtaining
proposed
high enough
to be
low levels of dietary
users or nonusers in life-style
to
by women
the
vitamin
between similar
use
women
results
possibility
that
serum micronutrient
for only
levels
( 17).
case-control
frequency
No one of the
but our ability
use of multivitamins
high and relatively
colleagues achieve
fruits
across different
A and C and folic acid was found
either
those
carotenoids
use of supplemental
strongly,
that the association
and
study of this neoplasm
risk of vulvar cancer,
study
risk more
is most likely due to differences
to affect carcinogenesis at increased
on risk among
carotenoids
years of intake.
of the common
Dietary
points
( 17). Particular
only on selected
with self-reported
increasing
at relatively
vitamins.
patterns
to take
cervical
with
to give
has yet to be determined.
vitamins
women
no effect These
practices
because
food diaries, at two different
for the individual
of individual
to influence
supplemental
among
to the one employed
were available
effect associated minimally
respective
had
supplements. who
the variability
this issue was limited
equally
our findings
have been
using food fre-
levels in serum or plasma
in interpreting
but risk increased
five vitamins
intake
with micronutrient
might
diet
similar
to the same individuals
values for the five carotenoids
We observed
usual adult
instruments
to their nutrient
cancer
to agree well with more exhaustive
In addition,
growing
in assessing
administered
be exercised
with respect
diet and vulvar
have been described,
in this study have been shown comparable
misclassified
between
and
intake.
indicated
compared there
were
.4s neither that
caffeine,
reported
that coffee drinkers
to nondrinkers irregular
changes
our study a primary
nor
were
(13). The effect for coffee the
ingredient
in risk with study
increased
by Mabuchi
in coffee
with
carcinogenic activity (28), influences vulvar cancer risk, the most probable for the observed association is unidentitied confounding.
and
possible
explanation
This study supports the report by Mabuchi and colleagues (13) that neither ethanol consumption nor intake of specific types of alcoholic beverages is associated with vulvar cancer.
With
respect
study were not shown
to the amount to he at excess
liquor did not appreciably risk factors. that
alter
of ethanol
consumed,
risk. In addition,
risk, after controlling
the heaviest intake
of wine,
for sexual
drinkers beer,
behavior
in this
and hard and other
A major concern in interpreting our results is the low response rate. The possibility participation was related to dietary intake and that our results are in some
436
AEI’ Vol. I, No. 5 August 1991: 427-437
Sturgeon et al. DIET AND THE RISK OF VULVAR CANCER
way biased
cannot
be excluded.
nonrespondents,
there
likely to participate. study
In addition,
is comparable
to that
17). It IS also reassuring identified
several
partners,
cigarette
there
Despite factors
that
suspected
research
directed
may provide
subjects
be noted
that even
including
anticancer
study
warts
sexual
(2).
While was
practices.
do not suggest that dietary
cancer
with
vulvar
cancer,
of dark yellow-orange
the role of diet is not yet
dietary
risk factors
(17). This study does suggest,
the potential
in this
every attempt
to their usual adult dietary
in cervical
on
rates (11,
multiple
of genital
or orher correlates
into the role of nutrition
data
observed
response
in this study,
to any of the postulated
cancer
levels
rusk are associated
of alpha carotene
toward
insight
cancer, history
cancer
limited
of data from this case-control
case recall
cervical
risk was not related cervical
analysis
intake
with higher
of this study, the data presented
exception
study of invasive
studies
the
age or racial groups were less
of dietary
for vulvar
and control
to influence
It should
we examined
and a self-reported
the limitations
vegetables. resolved;
an earlier
of differential
case patients
with the possible
the range
risk factors
smoking,
postulated
when
that particular
in epidemiologic
is also the possibility
made to orient
However,
was no indication
however,
activity
in a recent
that additional
of individual
in carcinogenesis
carotenoids
and cancer
prevention.
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KEY WORDS:
Vulvar cuncer, diet, carotenoids,
alpha carotene
INTRODUCTION Carcinoma
of the vulva
incidence
rate for invasive
vulvar
women/y
(1). Risk factors
associated
for cervical
cancer
of genital
warts,
and include
cervical
cancer
status
multiple
squamous-cell
and vulvar
cancer
have
sexual
the average
(3).
cancer
annual
cigarette
on Papanicolaou
evidence
2/100,000
to those
reported
smoking, smear
associated
frequent
age-adjusted
is less than
are similar
consistently
The
further
States
partners,
tinding
also been
tumors provides
tumor;
in the United
with vulvar
and a prior abnormal
of low socioeconomic predominantly
is a rare gynecologic
(2). Indicators with
simultaneous
for a possible
a history these
two
occurrence
of
common
etiology
(4). Recent might
attention
explain
that persists found
dietary
enoids
(58),
has focused
the association after adjustment intake
of dark green or orange
dysplasia
and vitamin
or neoplasia
than
vegetables C (6,9-l
among
with folic acid has been associated users of oral contraceptives
We evaluated
the relation
between
from a large case-control
the etiology
of cervical
cancer
study,
status
dietary
deficiencies
and cervical
risk factors.
Some
(5, 6), vitamin
cancer studies
A (7), carot-
1) to be lower among
comparison
dysplasia obtained
certain
and other
supplementation among
that
low socioeconomic
for sexual behavior
fruit juices (6,9),
with cervical
on the possibility
between
individuals.
individuals In addition,
with an improvement
in cervical
( 12). diet and vulvar to determine
also influence
cancer if dietary
using interview factors
the risk of vulvar cancer.
implicated In addition,
data in we
428
AEP Vol. 1, No. 5 August 1991: 427-437
Sturgeon et al. DIET AND THE RISK OF VULVAR CANCER
examined the roles of coffee and alcohol and vulvar lated as risk factors for vulvar cancer in a case-control
cancer because these were postustudy by Mabuchi and colleagues
(13).
METHODS Details
on the selection
are presented confirmed
elsewhere vulvar
participating subjects
of case patients
hospitals
diagnosed
for age (i-year Care
interviews
were obtained
Reasons
for nonresponse
control
subjects),
addition,
moved
or inability
having
3%),
exchange
for controls
under
rosters
for those
(61%)
and 348 control
to locate
and other
it was not possible
subjects
versus 34% of
(4% versus 9%),
problems
(2% versus
to obtain
the
65 and older.
death
3%).
physician
In
consent
an interview.
A structured mation
refusal
(6% versus
(telephone
techniques
at 34
of 686 control
( 18% of case patients
included
illness
identified
A total
race, and residence
digit dialing
study methods
and pathologically
1987 were
York.
from 209 case patients
for 6% of the case patients
to conduct
New
Administration
subject
and other
with incident
1985 and
upstate
age groups),
Financing
(51%).
1%))
and
using random
Home
(3% versus
between
in Chicago
or zip code) were selected age of 65 or Health
subjects,
(2). Briefly, 344 case patients
cancer
matched
and control
interview
on hypothesized
was administered
risk factors,
by trained
including
interviewers,
demographics,
to obtain
infor-
history,
men-
pregnancy
cigarette smoking, sexual and contraceptive strual history and hygiene practices, behavior, medical events, and diet. Diet was assessed using a food frequency questionnaire that included folate
the major food sources
in the diets of whites,
each
of 61 food
changes”
items,
subjects
to be consumed
data collected
in the
Food Consumption or “don’t
know”
analyses.
Survey responses
(16).
“usual
an approximate
Fourteen
A, carotenoids, in the United adult
per day, week,
US Department
intake, month,
season (8 cases,
subjects
included
on 99% of the food items of interest.
The
15). For
ignoring
recent
was assigned
(USDA) 6 controls)
in the study,
C, and
(14,
or year. For foods
length
of Agriculture
subjects
vitamin
States
with missing from the
complete
mean
from
Nationwide
for five or more of the food items were excluded
For the remaining
tion was available
their
of servings
seasonally,
1977-78
of vitamin
and Hispanics
provided
in terms of the number
reported
dietary
blacks,
informa-
ages of the tinal
dataset of 201 case patients and 342 controls were 53.9 and 52.6 years, respectively. Non-Hispanic whites comprised 86.5% of the case patients and 85.6% of the controls. Analyses and nutrient frequencies intake
of the dietary intake.
of consumption
was calculated
food items containing
data were conducted
Food group
intake
of the food
as the weighted the nutrient;
using measures
was calculated items
incuded
servings of the food. Portion size, food preparation practices, of a food item were estimated using methods
food group
in the food group.
sum of the frequencies
weights
of both
as the sum of the reported of consumption
used were the nutrient
contents
Nutrient of the of typical
and nutrient content of a typical serving described by Ziegler and associates ( 17).
Estimates obtained
of portion size and preparation practices were hased on 24-hour dietary recalls on a representative sample of the US population (Second National Health values and Nutrition Examination Survey (NHANES II)) (15). Th e f00 d composition assigned were an updated version of the values used in NHANES 11 (18). Estimates of
vitamin A and carotenoids beta carotene has one-sixth (19).
Folate
content
were updated according to the current convention that the vitamin A activity of an equivalent intake of retinal tables was obtained from the 1978-88 USDA foo d composition
Sturgeon et al. DIET AND THE RISK OF VULVAR CANCER
AEP Vol. 1, No. 5 August 1991: 427-437
(20) with updated (21).
Estimates
information
from recent
of five major
carotenoids
vegetables were obtained ments from the USDA and nutrient
intakes
laboratory
and proprietary
in approximately
from published reports (Beecher GR, personal
were treated
research
as categorical
sources
30 common
(22) and recent communication, exposure
429
fruits
and
preliminary measure1990). Food group
variables;
each measure
was
stratified into quartiles based on the frequency distribution in the control group. Subjects were also asked whether they had used supplemental vitamins on a regular basis and, subjects
if so, for how many years. For the measurement were queried
individual
supplements
In addition,
respectively and vulvar
and intensity
RRs of the
Weekly
and hard liquor yields
ethanol
of
intake
was
1.1, 2.9, and 9.4 g of
were 8, 4, and 1 fl oz, respectively
adjustment
techniques
partners,
indices
exsmoker,
(23).
intervals
A caffeine
history
any of the estimates.
as continuous
in a regression
using
explored
herpes
in-
or warts,
result on Papanicolaou New only
York,
Chicago).
for age,
of sexual partners, exposure
cigarette
since further
Tests for linear
a score to each level of a categorical
the variable
Adjusted
of genital
adjusted
and number
exposures
confounders
abnormal
were
dietary
risk (RR).
(CI) were derived
Potential
a previous
presented
change
between
of relative
and study area (upstate
nonsmoker),
did not materially by assigning
smoking,
age, race,
dietary
(25).
a self-reported
of cigarette
various
of association
as an estimate
and 95% confidence
regression
education,
(current,
treating
per day,
a cupful of tea and coffee yields 60 and 90 mg of caffeine,
estimates
of sexual
income,
obtained
wine,
taken.
on usual adult consumption
and tea was also obtained.
was the odds ratio,
logistic
number
smoking
usual adult
Information
used to assess the strength
likelihood
unconditional
smear,
consumption
assuming
cancer
maximum
duration
typically
and spirits.
intake,
(24).
The measure
cluded
of multivitamins their
usual servings
index was estimated
vitamin
brand
1 fl oz of beer,
and that
of specific
A, C, and E and folic acid as
about
coffee,
assuming
ethanol,
use of vitamins
were asked
of beer, wine,
decaffeinated
estimated
their
and the name
subjects
week, or month coffee,
regarding
variable
trend
were
and then
model.
RESULTS
Food Groups and Micronutrients Table
1 presents
the RRs of vulvar cancer
of dark yellow-orange
vegetables
was related
cancer,
to vulvar
lowest quartiles of dark green
of intake. vegetables,
legumes,
including
of citrus
and juices
such
as broccoli,
was also unrelated
vegetables,
fruits and juices,
risk of vulvar cancer complex
Table 2 presents risk estimates supplements. There were no trends C, vitamin
A, carotenoids,
with food groups. pumpkin, elevated
in risk were observed
green and black-eyed
between
carrots,
with risk estimates
No trends
association
associated
including
spinach,
among
women
with decreasing
turnip
peas and green,
Reduced
sweet potatoes,
greens,
in the two consumption
and collards,
lima, and pinto beans.
to risk. Furthermore,
there
meat,
or
Intake
was no consistent
and intake of the basic food groups, carbohydrates,
intake
and yams
including
and dairy products.
for micronutrients, excluding intake from vitamin in risk associated with decreasing intake of vitamin
or folate.
Individual Carotenoids In Table
3, vulvar
cancer
risk is presented
in relation
to estimated
dietary
intake
of
individual carotenoids, including alpha carotene, beta carotene, lutein, lycopene, and cryptoxanthin. The RRs for women in each the three lowest quartiles of alpha carotene intake were elevated. Intake of the other individual carotenoids was unrelated to risk.
430
Sturgeon et al. DIET AND THE RISK OF VULVAR CANCER
TABLE 1 food groups
Relative
mks
Food group (servings/w)
Dark yellow-orange vegerahles Ql 2 2.6 Q2 1.5-2.5 Q3 .7-1.4 (24 5 .6Y
Al? Vul. I, No. 5 August 1991 427-437
(RRs) of vulvar
cancer
associated
Cases (n = 201)
with
Controls (n = 342)
38 6L1 66
86 86 87 ni
Q4 5 2.4
60 45 51 45
Legumes Ql 2 5.7 Q2 3.7-5.6 43 2.3-3.6 44 5 2.2
37
intake
of selected
Adjusted RRs” (95”/0 CI)
1.00
.Y3 1.4’) 1.59 I’tru
(.5%1.6) (.Y-2.6) (.Y-2.7) trend = .O3
88 Yl 78 85
1.00 .71 1.04 .il 1’for
(.4-1.2) (.6-1.7) (.4-1.2) trend = .41
60 43 58 40
87 84 86 85
1.00 .80 1.11 .70 P for
(.5-1.1) (.7-1.8) (.4-1.2) trend = .40
Citrus fruits and Juices Ql 2 10.3 42 7.1-10.2 43 3.2-7.0 Q4 5 3.1
49 50 39 63
85 86 86 85
1.00 1.11 .78 1.20 I’ior
(.7&1.Y) (.5-1.4) (.iP2.0) trend = .73
Vegetables Ql 2 21.5 Q2 16.3-21.4 Q3 11.8-16.2 44 5 11.7
56 38 45 62
8i 84 87 84
1.00 .76 .76 l.OY I’for
(.i-1.3) (.5-1.3) (.7-1.8) trend = .72
Fruts Ql Q2 43 44
and jutes 2 20.9 13.9-20.8 9.0-13.8 5 8.9
56 44 34 67
86 85 87 84
1.00 .7Y .54 1.01 P fur
(.5-1.3) (.3-.Y) (.6-1.7) trend = .76
Complex carbohydrates Ql 2 18.1 Q2 13.4-18.0 43 10.4-13.3 Q4 5 10.3
61 55 41 44
86 86 86 84
1.00 .Y6 .70 .77 P for
(.6-1.6) (.4-1.2) (.5-1.3) trend = .19
Meat Ql Q2 Q3 Q4
58
46 51 46
86 86 85 85
1.00 .86 .Y7 .70 P for
(.5-1.4) (.6-1.6) (.4-1.2) trend = .27
46 53 54 48
86 86 a7 83
1.00 1.06 1.15 1.00 I’for
(.6-1.8) (.7-1.9) (.6-1.7) trend = .Y3
Dark green vegetables (21 2 6.0 (22 4.3-5.9 43 2.5-3.9
2 13.0 9.4-12.9 7.0-9.3 5 6.9
Dairy products Ql 2 16.4 Q2 11.1-16.3 Q3 6.5-11.0 Q4 5 6.4
’ Adjusted for age, number of sexual partners, and cigarette smokmg.
AEP Vol.
Sturgeon et al. DIET AND THE RISK OF VULVAR CANCER
I, Ntr. 5
August 1991. 427-437
TABLE
2
Relative
risks (RRs)
of vulvar
431
cancer associated with estimated intake of
selected micronutrients Micronutrient
Cases (n = 201)
Controls (n = 342)
Adjusted RR+ (95% CI)
Vltanm c (mgid) Ql 2 203 Q2 153-202 Q3 112-152 Q4 5 111
55 42 37 67
85 86 86 85
1.00 .86 (.5-1.4) .71 (.4-1.2) 1.15 (.7-1.9) P tar trend = .72
bl 43 40 57
85 86 86 85
1.00 .71 .67 .93 1 for
A (REld) QI 5 1465 Q,! 1067-1464 Q, 779-1066
Vitanun
Q4 5 778 Carotenolds (RE/d)h Ql 2 736 Q.2 521-735 Q, 369-520 Q4 5 368 Folare &id) Ql 2 299 Q2 233-298 Q1 180-232 Q4 5 179
(.4-1.2) (.4-1.1) (.6-1.5) trend =
.71
53 37 41 70
85 86 86 85
1.00 .73 (.4-1.3) .69 (.4-1.2) 1.20 (.7-2.0) I’ for trend = .47
54
85 86 86 85
1.00 .93 .68 1.02 P for
50 39 58
(.6-1.6) (.4-1.2) (.6-1.7) trend = .77
A strong correlation was observed between intake of dark yellow-orange vegetables and alpha carotene because dark yellow-orange vegetables are the major source of alpha carotene (Spearman’sr = .79, P = .OOOl). A s sh own in Table 4, it was not possible to assess the independent effects of these two dietary exposures on risk because so few women had discordant intake levels of dark yellow-orange vegetables and alpha carotene.
Supplemental Vitamins Table 5 shows the RRs associated with years of supplemental vitamin use. Combining intake from individual vitamins and multivitamins, risk was substantially lower among users of vitamins C, A, and E and folic acid. Multivitamin users were also at lower risk than were nonusers. Limiting comparisons to within vitamin takers only, however, no reductions in risk were observed with increasing years of use of vitamin A or multivitamins. Only modest decreasing trends in risk were noted with increasing years of use of vitamins C and E and folic acid. To estimate the combined effect of diet and vitamin intake, we examined the risks associated with years of supplemental vitamin intake of vitamins A and C and folic acid among women at each level of dietary intake of these nutrients. The effect of dietary intake of vitamins A and C and folate was also examined separately among users and nonusers of the respective supplemental vitamin (data not shown). Similar protective effects for supplemental vitamins A and C and folic acid as shown in Table
432
Sturgeon et al. DIET AND THE RISK OF WLVAR CANCER
AEP Vol. I, No. 5 Augwt 1991: 427-437
TABLE 3 Relative risks (RRs) of vulvar cancer associated with estimated individual carotenoids
intake of
Carotenoid
Cases (n = 201)
Controls (n = 342)
Alpha carotene (/q/d) (21 2 569 Q2 350-568 43 207-349 Q4 2 206
32 55 52 62
85 86 86 85
Beta carotene (pgld) (21 2 3006 (22 2048-3005 Q3 1284-2047 Q4 5 1283
44 41 54 62
85 86 86 85
Lutein &Id) Ql 2 4571 Q2 2784-4570 Q3 1279-2783 Q4 c 1278
54 54 42 51
85 86 86 85
1.00 1.02 (.6-1.7) .87 (.5-1.5) .98 (.6-1.6) P for trend = .81
Lycopene (pgld) (11 2 368 (12 259-367 Q3 170-258 (24 5 169
53 46 57 45
84 87 86 85
1.00
Cryptoxanthin @g/d) Ql 2 289 Q2 186-288 Q3 126-185 Q4 5 125
49 43 50 59
85 86 86 85
Adjusted RRs (95% CI)
1.00
1.60 1.56 1.74 P for
(.9-2.8) (.9-2.7) (1.0-3.0) trend = .09
1.00
.88 (.5-1.5) 1.23 (.7-2.1) 1.26 (.7-2.1) P for trend = .23
.81 (.5-1.4) 1.23 (.7-2.1) .79 (.5-1.3) P for trend = .76 1.00
.79 (.5-1.3) .94 (.6-1.6) .97 (.6-1.6) P for trend = .36
a Adjustedfor age, cigarettesmoking,and numberof sexualpartners
among women in each quartile of dietary intake of vitamins A and C and folate. On the other hand, no relationship between risk and dietary intake of vitamins A or C or folate was observed among either users or nonusers of the respective supplement. Closer evaluation of the effects of specific vitamins was limited because most women reported using multivitamins containing vitamins A, C, and E and folate, or individual supplements in combination with multivitamins. Among the 253 women taking vitamins C, E, or A or folic acid, 62% were taking all four, 14% were taking a combination of three, and 9% were taking a combination of two. Among women taking only one vitamin, 24 were taking vitamin C, six were taking vitamin E, and two were taking folic acid; no women reported taking only vitamin A.
5 were evident
Coffee and Alcohol
Consumption
The relationship of risk to consumption of caffeinated and decaffeinated hot beverages is shown in Table 6. Although risk was modestly elevated among women consuming more than three cups of coffee per day even after adjustment for age, sexual behavior, and cigarette smoking (RR = 1.72; CI, 1.0 to 3.0), the pattern of increasing risk with
433
sturgeon et al. DIET AND THE RISK OF VULVAR CANCER
AEP Vol. I, No. 5 August 1991: 427-433
TABLE 4 Relative risks” of vulvar cancer associated with level of intake of alpha camtene and dark yellow-orange vegetables Quartile Quartile of dark yellow-orange vegetable intake
(24 (Low) for age,
’ In parentheses
’Referent
cigarette
smoking,
are numbers
of cahe
and
Q4
.8@ (1,2) .96 (1@,22) 1.52 (X43) 1.42 (13,19)
.9i
1.00
Q3
(23
(Low)
(9.20) 1.08 (22,45) 2.18 (18,li) 2.69 (6.4)
(26,63) .51 (4.15) .39 (1,4) .6i (1.3)
Q2
intakeh
Q2
(I-&h)
Ql Wish)
’-4djusted
of
alpha carotene
number
pat~enrs
and
of cexu~l control
3.70 (1.1) l.Oi (2,4) 1.18 (13,23) 1.61 (46,57)
pxtncra.
suh]rcr~
category.
increasing
coffee
wasalso
consumption
was irregular.
Among
nonsmokers,
the pattern
(RR = 1.0, 1.75, 1.47, 1.37, 1.79). C onsumption
irregular
coffee and tea was unrelated
to risk. The caffeine
index
of risk
of decaffeinated
also showed
no clear relation
with risk. There
was no association
risk of vulvar including
cancer
beer,
with increasing
(data
wine,
between not
and spirits
intake
the overall
shown).
When
amount
were examined,
after adjustment
types
risk was not appreciably
increased
for age, sexual behavior,
between Dietary Risk Factors if the dietary
confounded
intake,
supplemental
regression There
by each
model
vitamin
along
with
was no evidence
and cigarette
factors found to be associated
other,
dark
yellow-orange
of confounding
smoking,
or alpha
were entered
and number
as the risk estimates
smoking.
with risk in this study
vegetable
use, and coffee consumption age, cigarette
and
beverages
Finally, were
consumed
of alcohol
Interrelationship to determine
of ethanol
specific
of sexual
presented
carotene
together
into a
partners.
earlier
in the
text were unchanged.
TABLE
5
Relati\ze risks” of vulvar cancer associated with years of supplemental Years
Type of vitamin
Vitamin C Vltamm A Vwmm E Fohc acd Multivitamins
0
1.0 (123,162) 1.0 (135,193) 1.0 (123,180) 1.0 (141.208) 1.0 (135,186)
l-3 .65 (16,33) .66 (12,25) .86 (17,28) .74 (12.23) .58 (11326)
4-9
.68 (22,4L1) .i!
(15,28! .85 (21935) .79 (li,Jii .i9
(13,30)
vitamin use
taken”
10-15 .iS
(13,32) .44 (8,26) .50 (9.26) ,517 (7,221 .41 (11,38)
16+ .47 (22.65) .i6 (X.53) .ii (22.611)
P for trend cm6
,177 .09
.i9
.I1
(l&44) .i9 (li,41)
.08
Unknown .ii
(5.10) 1.1: (Il,li) 1.23 (9.13) 1.X (10,181 1.Z (14.21)
434
AEP Vol. 1, No. 5 Augwt 1991: 427-437
Sturgeon et al. DIET AND THE RISK OF VULVAR CANCER
TABLE 6 Relative risks (RRs)” of vulvar cancer associated with intake of caffeinated decaffeinated beverages Beverage
Cases
Unadjusted RRs
Controls
and
Adjusted RRs (95% CI)
coffee(cups/d) 0
105 99 48 41 49
48 51 35 LO 47
3 4+ Decaffeinated coffee (cups/d) 0 Ii
I.00
1.00 i.lY (.7-2.0) 1.59 (.Y-2.9) 1.03 (.5-2.0) 1.72 (1.0-3.0) P for trend = .OY
1.13 1.60 l.t?i 2.09
134 48 19
202 104 36
1.00
56
69 221 30 22
1.00
114 17 14
13 34 47 49 58
24 79 80 82 77
1.00
1.00 .77 (.5-1.2) .89 (.i-1.7) I’ for trend = .40
.io .80
Tea (cups/d) 0 2 3+ Caffeme Index (mgid) 0 1-63 64-154 155-271 272i
1.00 .66 (.4-1.0) .77 (.4-1.6) 1.172 (.4-2.3) P for trend = .71
.64 .iG .78
1.02 .i6 (.3-1.7) 1.11 (.5-2.5) 1.13 (.5-2.5) 1.21 (.i-2.7) P hr trend =
.80
1.09 1.10 1.39
(18
DISCUSSION Among
the various
food groups,
cancer.
An increased
and Individual
micronutrients,
in this study, only twc> closely correlated
dietary
risk of vulvar cancer
exposures
was observed
carotenoids
were associated
among
wOrnen with decreased
intake of dark yellow-orange vegetables or alpha carotene. However, separate an alpha carotene effect from the effect of dark yellow-orange se because study,
the rncjst common
carrota,
is rich
in alpha
dark yellow-orange carotene
vegetable
and there
are only
eaten
we found no beta carotene
A carotenoids therefore
effect using either
or with beta carotene
inconsistent
measured
with the findings
USDA
directly.
of protective
The
we could vegetables
by women
a few sources
carc>tene other than dark yellow-orange vegetahles (e.g., peaches, Dark yellow-orange vegetables are also a rich dietary source however,
examined with vulvar
corn). of beta
estimates results
not per
in this of alpha
carotene;
of provitamin
of this study are
effects of beta carotene
that have
been reported in several studies of cervical cancer (5-8). On the other hand, our results are in agreement with a large study of in situ cervical cancer in which provitamin A carotenoids were not associated with risk hut dark yellow-orange vegetable intake did appear tc>exert some protective effect (26). Furthermore, Murakoshi and colleagues (27) reported that alpha carotene has nearly ten times the antiproliferative activity of beta carotene plausibility
on a human of our finding
retinoblastoma an effect
cell line, providing
for alpha
carotene
evidence
for the biologic
but not for beta carotene.
435
Sturgeon et al. DIET AND THE RISK OF VULVAR CANCER
AEP Vol. I, No. 5 August 1991: 427-437
A relationship (4, 5), though
of dietary
risk of vulvar
cancer.
fruits and juices,
C with cervical
Intake
that
of vitamic
dark green vegetables)
subjects. The rationale
for suspecting
from a small clinical regressed
vitamin
our data do not indicate
consistent
cancer
risk has been
vitamic
C intake
suggested
increases
the
C or foods rich in this compound
(i.e.,
was similar
and control
between
case patients
that folate might affect risk of vulvar cancer
trial in which
cervical
on folic acid administration
risk is, however,
reduced
dysplasia
citrus
is derived
in users of oral contraceptives
(12). The lack of a folate effect on vulvar cancer
with several
case-control
studies
of cervical
cancer
(9, 17,
26). If individuals intake,
in this study were seriously
underlying
obscured. quency
true associations
Although
potential
questionnaires
problems
results
when
in time,
and to correlate
caution
should
because
laboratory
and vegetables. foods, vitamins examine
seasons,
and cooking
a protective
examined
in this study.
Taking
protective of these
however,
appeared
with vulvar cancer choose
invastve women
taking
in this
suggest
vitamins
cancer,
and
Ziegler
supplemental
An earlier
vitamins
intake
was modest
of coffee
colleagues
(13)
of vitamins
who
A and C and folacin, of these
respective
of supplemental
do not.
factors
Obtaining
proposed
high enough
to be
low levels of dietary
users or nonusers in life-style
to
by women
the
vitamin
between similar
use
women
results
possibility
that
serum micronutrient
for only
levels
( 17).
case-control
frequency
No one of the
but our ability
use of multivitamins
high and relatively
colleagues achieve
fruits
across different
A and C and folic acid was found
either
those
carotenoids
use of supplemental
strongly,
that the association
and
study of this neoplasm
risk of vulvar cancer,
study
risk more
is most likely due to differences
to affect carcinogenesis at increased
on risk among
carotenoids
years of intake.
of the common
Dietary
points
( 17). Particular
only on selected
with self-reported
increasing
at relatively
vitamins.
patterns
to take
cervical
with
to give
has yet to be determined.
vitamins
women
no effect These
practices
because
food diaries, at two different
for the individual
of individual
to influence
supplemental
among
to the one employed
were available
effect associated minimally
respective
had
supplements. who
the variability
this issue was limited
equally
our findings
have been
using food fre-
levels in serum or plasma
in interpreting
but risk increased
five vitamins
intake
with micronutrient
might
diet
similar
to the same individuals
values for the five carotenoids
We observed
usual adult
instruments
to their nutrient
cancer
to agree well with more exhaustive
In addition,
growing
in assessing
administered
be exercised
with respect
diet and vulvar
have been described,
in this study have been shown comparable
misclassified
between
and
intake.
indicated
compared there
were
.4s neither that
caffeine,
reported
that coffee drinkers
to nondrinkers irregular
changes
our study a primary
nor
were
(13). The effect for coffee the
ingredient
in risk with study
increased
by Mabuchi
in coffee
with
carcinogenic activity (28), influences vulvar cancer risk, the most probable for the observed association is unidentitied confounding.
and
possible
explanation
This study supports the report by Mabuchi and colleagues (13) that neither ethanol consumption nor intake of specific types of alcoholic beverages is associated with vulvar cancer.
With
respect
study were not shown
to the amount to he at excess
liquor did not appreciably risk factors. that
alter
of ethanol
consumed,
risk. In addition,
risk, after controlling
the heaviest intake
of wine,
for sexual
drinkers beer,
behavior
in this
and hard and other
A major concern in interpreting our results is the low response rate. The possibility participation was related to dietary intake and that our results are in some
436
AEI’ Vol. I, No. 5 August 1991: 427-437
Sturgeon et al. DIET AND THE RISK OF VULVAR CANCER
way biased
cannot
be excluded.
nonrespondents,
there
likely to participate. study
In addition,
is comparable
to that
17). It IS also reassuring identified
several
partners,
cigarette
there
Despite factors
that
suspected
research
directed
may provide
subjects
be noted
that even
including
anticancer
study
warts
sexual
(2).
While was
practices.
do not suggest that dietary
cancer
with
vulvar
cancer,
of dark yellow-orange
the role of diet is not yet
dietary
risk factors
(17). This study does suggest,
the potential
in this
every attempt
to their usual adult dietary
in cervical
on
rates (11,
multiple
of genital
or orher correlates
into the role of nutrition
data
observed
response
in this study,
to any of the postulated
cancer
levels
rusk are associated
of alpha carotene
toward
insight
cancer, history
cancer
limited
of data from this case-control
case recall
cervical
risk was not related cervical
analysis
intake
with higher
of this study, the data presented
exception
study of invasive
studies
the
age or racial groups were less
of dietary
for vulvar
and control
to influence
It should
we examined
and a self-reported
the limitations
vegetables. resolved;
an earlier
of differential
case patients
with the possible
the range
risk factors
smoking,
postulated
when
that particular
in epidemiologic
is also the possibility
made to orient
However,
was no indication
however,
activity
in a recent
that additional
of individual
in carcinogenesis
carotenoids
and cancer
prevention.
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