Dietary Intake of Lycopene Is Associated with Reduced Pancreatic Cancer Risk

Nutrition and Cancer
Dietary Intake of Lycopene Is Associated with Reduced Pancreatic
Cancer Risk1
Andre´ Nkondjock,*† Parviz Ghadirian,* **2 Kenneth C. Johnson,‡ Daniel Krewski,†
and the Canadian Cancer Registries Epidemiology Research Group
*Epidemiology Research Unit, Research Centre, Centre hospitalier de l’Universite´ de Montre´al (CHUM)-Hoˆtel-
Dieu; †McLaughlin Centre for Population Health Risk Assessment, Institute of Population Health, University
of Ottawa, Ottawa, ON, Canada; **Department of Nutrition, Faculty of Medicine, University of Montreal,
Montreal, QC, Canada; and ‡Surveillance and Risk Assessment Division, Centre for Chronic Disease
Prevention and Control, Population and Public Health Branch, Health Canada, Ottawa, Canada
ABSTRACT
Although fruits and vegetables have been implicated in the etiology of pancreatic cancer, the role of
phytochemicals in these food groups has received little attention to date. In this study, we investigated the possible
association between dietary carotenoids and pancreatic cancer risk. A case-control study of 462 histologically
con?rmed pancreatic cancer cases and 4721 population-based controls in 8 Canadian provinces took place
between 1994 and 1997. Dietary intake was assessed by a self-administered FFQ. Unconditional logistic regres-
sion was used to assess associations between speci?c and total carotenoid intakes and the risk of pancreatic
cancer. All tests of statistical signi?cance were 2-sided. After adjustment for age, province, BMI, smoking,
educational attainment, dietary folate, and total energy intake, lycopene, provided mainly by tomatoes, was
associated with a 31% reduction in pancreatic cancer risk among men [odds ratio (OR) ? 0.69; 95% CI: 0.46 – 0.96;
P ? 0.026 for trend] when comparing the highest and lowest quartiles of intake. Both ?-carotene (OR ? 0.57; 95%
CI: 0.32– 0.99; P ? 0.016 for trend) and total carotenoids (OR ? 0.58; 95% CI: 0.34 –1.00; P ? 0.02 for trend) were
associated with a signi?cantly reduced risk among those who never smoked. The results of this study suggest that
a diet rich in tomatoes and tomato-based products with high lycopene content may help reduce pancreatic cancer
risk.
J. Nutr. 135: 592–597, 2005.
KEY WORDS: ? pancreatic cancer ? diet ? carotenoids ? lycopene ? cancer prevention
Pancreatic cancer is the 4th leading cause of cancer-related
suppresses cytochrome P
1A1, an activator of procarcino-
450
deaths in both men and women in Canada (1). Survival is
gens (6). ?-Carotene may control growth-inhibitory and pro-
extremely low worldwide, with a 5-y survival rate of ?5% (2),
apoptotic effects in cancer cells through the redox regulation
and a case fatality proportion of 99% within 12 mo of diagnosis
of the nuclear transcription factor NF-?B activity (7). Lyco-
(3). Several epidemiologic studies suggested that high con-
pene is the most ef?cient singlet oxygen quencher in vitro (8);
sumption of fruits and vegetables, which are major sources of
lutein and zeaxanthin are scavengers of radical oxygen species
carotenoids, may play a role in the prevention of pancreatic
(4), whereas ?-cryptoxanthin may stimulate the expression of
cancer. Substantial evidence from experimental investigations
RB, an anti-oncogene and p73, a p53-related gene (9).
showed that carotenoids precipitate cancer-preventing events,
Despite the mechanistic hypotheses suggesting that intake
including antioxidant activity, enhancement of immune func-
of carotenoids may be related to reduced pancreatic cancer
tion, stimulation of gap junctional intercellular communica-
risk, no epidemiologic studies have addressed this issue to date.
tion, induction of detoxifying enzymes, and inhibition of cel-
The present case-control study was undertaken to investigate
lular proliferation (4,5). It was suggested that ?-carotene
the possible association between the intake of speci?c and
total carotenoids and pancreatic cancer risk within the Cana-
dian
National
Enhanced
Cancer
Surveillance
System
1 Funded with the support of the Canadian Cancer Society through an award
(NECSS).3 This study also examined the modifying effect of
(A.N.) from the National Cancer Institute of Canada, the Natural Sciences and
Engineering Research Council of Canada, the Social Sciences and Engineering
smoking on the association between dietary carotenoid intake
Research Council of Canada, the McLaughlin Foundation, and Health Canada.
and pancreatic cancer risk because free radicals in cigarette
This project used data collected through the National Enhanced Cancer Surveil-
smoke can alter the concentrations of most carotenoids (10).
lance System, a collaboration of the Surveillance and Risk Assessment Division,
Centre for Chronic Disease Prevention and Control, Population and Public Health
Branch, Health Canada and the Canadian Cancer Registries Epidemiology Re-
search Group.
2 To whom correspondence should be addressed.
3 Abbreviations used: NECSS, National Enhanced Cancer Surveillance Sys-
E-mail: parviz.ghadirian@umontreal.ca.
tem; OR, odds ratio; USDA-NCC, USDA-Nutrition Coordinating Center.
0022-3166/05 $8.00 © 2005 American Society for Nutritional Sciences.
Manuscript received 4 November 2004. Initial review completed 22 November 2004. Revision accepted 29 November 2004.
592

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DIETARY CAROTENOIDS AND PANCREATIC CANCER RISK
593
SUBJECTS AND METHODS
the study questionnaire. Information on other nutrients, including
total carotenoids, dietary folate, and total energy, was obtained
Study population. The NECSS is a multisite, population-based,
through the 1997 Canadian Nutrient File.
case-control study involving 21,020 participants with 1 of 19 types of
Data were collected for 475 cases (264 men, 211 women) and
cancer identi?ed through cancer registries in 8 of the 10 Canadian
5039 controls (2547 men, 2492 women). We excluded controls
provinces, namely, Alberta, British Columbia, Manitoba, Newfound-
? 30 y of age (n ? 237) because pancreatic cancer cases are usually
land, Nova Scotia, Ontario, Prince Edward Island, and Saskatche-
?30 y old. Furthermore, subjects with daily energy intake ? 500 kcal
wan. The present investigation includes only pancreatic cancer cases,
(2.092 MJ) (10 cases and 54 controls) or ? 5000 kcal (20.92 MJ) (3
and is restricted to data obtained from direct interviews. The study
cases and 27 controls) were excluded because such intakes are unre-
population was described in detail elsewhere (11). Brie?y, between
alistic and hence of questionable validity. Finally, a total of 462 cases
April 1, 1994 and December 31, 1997, participating provincial reg-
(258 men, 204 women) and 4721 frequency-matched controls (2331
istries identi?ed pancreatic cancer cases as early as possible in the
men, 2390 women) were eligible for analysis.
registration process to minimize the loss of subjects because pancre-
Statistical analysis. Food intake among cases and controls was
atic cancer is a rapidly fatal disease. All pancreatic cancer cases
analyzed according to carotenoid intake based on the USDA-NCC
included in the NECSS were con?rmed histologically, and de?ned
Carotenoid Database and the Canadian Nutrient File noted previ-
according to the WHO’s International Classi?cation of Diseases,
ously. Mean intakes were calculated separately for cases and controls.
rubric 157 (12).
To compare the study population characteristics, we used the ?2 test
Like most other studies of pancreatic cancer that collected infor-
or Mantel extension test for categorical variables and the paired t test
mation directly from case subjects, the overall proportion of eligible
for continuous variables. To evaluate associations between carot-
cases that responded was low. Among men diagnosed with pancreatic
enoids and pancreatic cancer risk, the study subjects were divided
cancer, 30% had died before an interview could be conducted, and
into 4 categories on the basis of quartiles of total and each speci?c
consent was not granted by physicians for an additional 15%. For
energy-adjusted carotenoid intake in the control population. Odds
women, 28% had died before they could be contacted, and the
ratios (ORs) and 95% CIs were calculated using unconditional logis-
attending physician refused consent to approach patients for an
tic regression. Analyses were adjusted for matching variables (age
additional 16%. The vast majority of cases were ascertained within
group and province), lifetime cigarette consumption (0, ?0 –15, and
1–3 mo of diagnosis; physician consent to send questionnaires to
?15 pack-y), BMI (?25, 25–29.9, and ?30 kg/m2), educational
patients was generally obtained within 1 mo, and ?70% of question-
attainment (y), dietary folate, and total energy intake.
naires were returned within 2 mo of mailing. Response rates of
To evaluate the combined effect of intake of individual carot-
eligible cases were 55% for men and 56% for women.
enoids and selected lifestyle variables (smoking, BMI, age, and edu-
The NECSS used frequency matching in selecting the control
cational attainment), the P-value for a multiplicative interaction
population to achieve age and gender distributions similar to those of
term added to a fully adjusted model was examined; when it was
all cancer cases combined. Based on the projected number of incident
signi?cant, the analysis was strati?ed on that variable. Tests for linear
cancer cases by province, the questionnaires were mailed to 8117
trend in the carotenoid variables included in logistic regression were
subjects during the 1996 calendar year using the same protocol as for
performed by replacing the indicator variables in each multivariate
cases. Questionnaires were not returned for 573 controls (7.4%)
model with a single variable representing the median frequency of
because of incorrect or changed addresses. Strategies for control
consumption for a given intake category, and by using the Wald ?2
selection varied by province, depending on data accessibility. In
value computed for the regression coef?cient of this variable to test
Prince Edward Island, Nova Scotia, Manitoba, Saskatchewan, and
the null hypothesis of no linear trend in pancreatic cancer risk across
British Columbia, provincial health insurance plans were tapped to
quartiles of intake. This analysis focused on carotenoid intake from
obtain a random sample of the provincial population strati?ed by age
diet, rather from speci?c carotenoid supplements. At the time the
and gender. In each of these provinces, ?95% of residents are
study was conducted, questions about the consumption of such sup-
covered by public health care plans. Active military personnel and
plements were not included in the FFQ. Models were ?t for men and
their families as well as indigenous peoples were excluded because
women separately. All tests of statistical signi?cance were 2-sided and
they were covered by other plans. In Ontario, Ministry of Finance
P-values ? 0.05 were considered signi?cant. All analyses were con-
data were used to derive a strati?ed random sample, whereas New-
ducted using SPSS statistical software (release 10.02, SPSS).
foundland and Alberta adopted a random digit-dialing method to
enroll a population-based sample of controls. A total of 5039 controls
were selected to serve as a common control group for all types of
RESULTS
cancer. Response rates of 65 and 71% were achieved from the male
and female control populations, respectively.
Selected characteristics of the study population are pre-
Questionnaires, with telephone follow-up for clari?cation when
sented (Table 1). In both men and women, there were appre-
necessary, were mailed to study subjects to obtain information on
ciable differences between cases and controls for age distribu-
residential and occupational histories and other risk factors for can-
tions with an excess of younger control subjects (P ? 0.05); in
cer. The NECSS questionnaire included questions on smoking his-
addition, cases were more likely to use high amounts of to-
tory, height, weight, physical activity, and education attainment.
bacco (P ? 0.01). Two years before the diagnosis of cancer,
This research was approved by the ethics committee of Health
there was a higher pancreatic cancer risk with increased BMI
Canada and written, informed consent was obtained from each study
in both genders (P ? 0.05). Among men, cases were more
subject.
Dietary assessment. Food consumption data were obtained via a
likely to have greater total energy intake than controls (P
semiquantitative FFQ derived from 2 instruments developed in the
? 0.01).
United States that have been widely validated previously, i.e., the
The main food sources of ?-carotene in the diet were
short Block questionnaire (13) and the Willett questionnaire (14).
carrots and tomatoes. ?-Carotene was derived primarily from
Subtle changes were made to the questionnaire items to take into
potatoes, carrots, and spinach. ?-Cryptoxanthin was supplied
account differences in American and Canadian dietary practices. The
by oranges and fruit juices, whereas lycopene was mainly from
FFQ includes questions on 69 different food and beverage items,
tomatoes, tomato juice, and tomato sauce. Lutein ? zeaxan-
including the frequency of consumption and the amounts consumed.
thin were from broccoli and green-leaf vegetables, and total
Participants were asked how often they had consumed these foods per
carotenoids were mainly from potatoes, carrots, and canta-
week in the time period 2 y before interview.
Food and beverage items were retrieved from the FFQ and used to
loupes.
estimate the daily intake of individual carotenoids, based on the
The ORs and corresponding 95% CIs for pancreatic cancer
USDA-Nutrition Coordinating Center (NCC) Carotenoid Database
according to speci?c and total carotenoid intakes are summa-
(15). This online database provides food composition values for 6
rized (Table 2). After adjustment for age, province, educa-
speci?c carotenoids contained in food and beverage items included in
tional attainment, smoking, BMI, folate, and total energy

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594
NKONDJOCK ET AL.
TABLE 1
Selected characteristics of the study population1
Men (n ? 2589)
Women (n ? 2594)
Cases (n ? 258)
Controls (n ? 2331)
Cases (n ? 204)
Controls (n ? 2390)
n (%)
Age, y
30–34
2 (1)*
124 (5.5)
3 (1.5)†
62 (3)
35–39
6 (2)*
140 (6)
2 (1)†
124 (5)
40–44
6 (2)*
109 (4.5)
12 (6)†
224 (9)
45–49
15 (6)*
113 (5)
13 (6.5)†
335 (14)
50–54
27 (11)*
152 (7)
21 (10)†
274 (11)
55–59
33 (13)*
217 (9)
25 (12)†
269 (11)
60–64
52 (20)*
350 (15)
33 (16)†
351 (15)
65–69
62 (24)*
537 (23)
53 (26)†
377 (16)
70–74
55 (21)*
589 (25)
42 (21)†
374 (16)
Cigarette consumption, pack-y
0
57 (22)†
571 (25)
87 (43)†
1196 (50)
?0–15
48 (19)†
706 (30)
45 (22)†
678 (28)
?15
150 (58)†
1026 (44)
69 (34)†
491 (21)
Missing
3 (1)
28 (1)
3 (1)
25 (1)
BMI 2 y before diagnosis, kg/m2
?25
86 (33)*
882 (38)
102 (50)†
1353 (57)
25–29.9
118 (46)*
1099 (47)
55 (27)†
717 (30)
?30
54 (21)*
350 (15)
47 (23)†
320 (13)
Physical activity,2 h/mo
?21
75 (29)
563 (24)
59 (29)
605 (25)
21–23
120 (47)
1207 (52)
108 (53)
1343 (56)
?23
62 (24)
561 (24)
37 (18)
442 (19)
Daily energy intake, kJ/d
8268 ? 3511†
7549 ? 2822
7265 ? 2541
6859 ? 2491
1 Values are means ? SD or n (%). Symbols indicate different from controls: * P ? 0.05; † P ? 0.01.
2 De?ned as total number of hours per month of moderate and vigorous activities.
intake, a signi?cant inverse association was observed between
Previous observational investigations assessed the relation
pancreatic cancer risk and lycopene intake in men (OR
between lycopene serum concentrations and pancreatic cancer
? 0.69; 95% CI: 0.46–0.96; P ? 0.026 for trend), when
with consistent results. A case-control study found that plasma
comparing the highest quartile of intake with the lowest.
lycopene levels were signi?cantly lower in pancreatic cancer
Intakes of ?-carotene, ?-carotene, ?-cryptoxanthin, lutein/
cases than in matched controls (16). In the Washington
zeaxanthin, and total carotenoids were not associated with
County Cohort Study, in which subjects were followed for
pancreatic cancer risk.
almost 15 y, signi?cantly lower baseline serum lycopene levels
There was evidence of an interaction between tobacco use
were documented in subjects with pancreatic cancer than in
and ?-carotene (P ? 0.02) as well as total carotenoids (P
matched cohort controls (17,18). Lower serum lycopene levels
? 0.013). The risk of pancreatic cancer in relation to intake
were observed in individuals with certain chronic diseases,
of carotenoids is presented by level of tobacco consumption
including cancer, suggesting that lycopene intake reduces the
(Table 3). Among those who never smoked, inverse dose-
occurrence, extent, or degree of these conditions, or that
response relations were apparent between ?-carotene (OR
lycopene is depleted by oxidative stress and in?ammatory
? 0.57; 95% CI: 0.32–0.99; P ? 0.016 for trend) and total
processes (19). Interestingly, in vitro studies suggest that ly-
carotenoids (OR ? 0.58; 95% CI: 0.34 –1.00; P ? 0.02 for
copene inhibits gap junction communication (20), activates
trend) and pancreatic cancer, when comparing the highest
phase II enzymes (21), suppresses eicosanoid metabolism by
with the lowest quartile of intakes. These results did not differ
blocking cyclooxygenase-2 synthesis (22), and inhibits tumor
among subgroups de?ned by pack-years of cigarette smoking.
cell growth by repressing insulin-like growth factor 1 receptor
Overall, there was no signi?cant effect modi?cation by BMI,
activation (23). However, these putative mechanisms remain
age, physical activity, and educational attainment (data not
speculative and require con?rmation.
shown).
We observed a 42% reduction in pancreatic risk in relation
to both ?-carotene and total carotenoids among those who
DISCUSSION
never smoked, but no clear evidence of an association between
This population-based case-control study demonstrated an
any individual or total carotenoid intakes and pancreatic can-
inverse dose-response relation between lycopene and pancre-
cer risk among past or current smokers. Exposure to tobacco
atic cancer in men. Intakes of ?-carotene and total carot-
smoke causes extensive ?-carotene oxidation (24). It was
enoids were signi?cantly associated with reduced pancreatic
reported that cigarette smoking is independently associated
cancer risk among those who never smoked. To the best of our
with lowered circulating concentrations of provitamin A carot-
knowledge, this is the ?rst epidemiologic study to examine the
enoids: in general, active smokers have ?25% lower circulat-
role of speci?c dietary carotenoids in risk assessment of pan-
ing concentrations of ?-carotene, ?-carotene, and ?-crypto-
creatic cancer.
xanthin than nonsmokers, even after adjusting for dietary

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DIETARY CAROTENOIDS AND PANCREATIC CANCER RISK
595
TABLE 2
Odds ratio (OR) and 95% CI for pancreatic cancer associated with dietary carotenoids1,2
Quartiles of energy-adjusted carotenoid intakes
P for
Carotenoid
Gender
1
2
3
4
trend
?-Carotene
Male
Dietary intake, ?g/d
358 ? 212
694 ? 284
1051 ? 214
2060 ? 1044
Cases/Controls, n
68/696
77/549
58/516
45/501
Multivariate OR (95% CI)
1.00
0.68 (0.46–0.98)
0.80 (0.54–1.19)
1.01 (0.67–1.53)
0.90
Female
Dietary intake, ?g/d
341 ? 182
651 ? 270
1013 ? 200
2059 ? 1147
Cases/Controls, n
45/443
42/590
58/623
51/638
Multivariate OR (95% CI)
1.00
1.65 (1.04–2.61)
1.31 (0.84–2.04)
1.56 (0.98–2.42)
0.13
?-Carotene
Male
Dietary intake, ?g/d
6215 ? 3832
10,621 ? 3522
15,788 ? 3173
25,763 ? 14,196
Cases/Controls, n
69/634
64/532
69/565
46/531
Multivariate OR (95% CI)
1.00
0.93 (0.63–1.38)
0.89 (0.61–1.30)
1.22 (0.80–1.87)
0.58
Female
Dietary intake, ?g/d
5953 ? 3387
9803 ? 2882
14,935 ? 3269
22,059 ? 10,683
Cases/Controls, n
40/505
39/607
61/574
56/608
Multivariate OR (95% CI)
1.00
1.30 (0.80–2.12)
0.83 (0.53–1.30)
0.96 (0.60–1.51)
0.40
P-Cryptoxanthin
Male
Dietary intake, ?g/d
77 ? 66
162 ? 83
267 ? 80
598 ? 314
Cases/Controls, n
75/676
77/565
51/524
45/497
Multivariate OR (95% CI)
1.00
0.73 (0.51–1.05)
1.02 (0.68–1.53)
1.09 (0.72–1.62)
0.46
Female
Dietary intake, ?g/d
837 ? 716
1139 ? 753
1951 ? 820
7234 ? 6510
Cases/Controls, n
52/462
37/575
52/615
55/642
Multivariate OR (95% CI)
1.00
1.50 (0.95–2.38)
1.26 (0.82–1.94)
1.23 (0.80–1.87)
0.27
Lycopene
Male
Dietary intake, ?g/d
898 ? 772
1215 ? 859
2106 ? 917
7585 ? 6505
Cases/Controls, n
56/651
58/536
63/518
71/557
Multivariate OR (95% CI)
1.00
0.78 (0.51–1.19)
0.76 (0.49–1.16)
0.69 (0.46–0.96)
0.026
Female
Dietary intake, ?g/d
837 ? 716
1139 ? 753
1951 ? 820
7234 ? 6510
Cases/Controls, n
42/487
41/604
48/621
65/582
Multivariate OR (95% CI)
1.00
1.38 (0.84–2.56)
1.05 (0.65–1.70)
0.91 (0.56–1.43)
0.27
Lutein ? Zeaxanthin
Male
Dietary intake, ?g/d
767 ? 380
1105 ? 382
1702 ? 499
3574 ? 1585
Cases/Controls, n
85/704
53/594
61/516
49/448
Multivariate OR (95% CI)
1.00
1.19 (0.81–1.74)
0.99 (0.68–1.44)
1.13 (0.76–1.68)
0.63
Female
Dietary intake, ?g/d
752 ? 368
1057 ? 348
1576 ? 418
3690 ? 1694
Cases/Controls, n
42/435
41/546
57/622
56/691
Multivariate OR (95% CI)
1.00
1.09 (0.68–1.75)
1.12 (0.70–1.78)
1.25 (0.79–1.98)
0.23
Total carotenoids
Male
Dietary intake,3 RE/d
1514 ? 955
2578 ? 851
3813 ? 729
6365 ? 3359
Cases/Controls, n
71/645
66/532
62/542
49/543
Multivariate OR (95% CI)
1.00
0.92 (0.62–1.36)
0.84 (0.58–1.23)
1.22 (0.80–1.86)
0.68
Female
Dietary intake, RE/d
1448 ? 848
2444 ? 696
3629 ? 759
5551 ? 2642
Cases/Controls, n
42/494 4
0/608
56/596
58/596
Multivariate OR (95% CI)
1.00
1.11 (0.69–1.78)
0.92 (0.58–1.44)
0.91 (0.58–1.44)
0.50
1 Values are means ? SD or OR (95% CI).
2 OR and 95% CI from the logistic regression model adjusted for age, province, smoking, educational attainment, BMI, folate, and total energy
intake.
3 De?ned as retinol equivalent.
intake and other demographic factors (10,25). Moreover, de-
of pancreatic cancer cases, and general population sampling.
pressed plasma ?-carotene concentrations were reported in
Ours is the ?rst study to examine the role of dietary carotenoid
response to enhanced metabolic turnover resulting from smok-
intakes in risk assessment of pancreatic cancer. The large
ing-induced oxidative stress (26). If this putative oxidative
sample size permitted subgroup analyses by sex and smoking
mechanism can be shown to affect the relation between ?-car-
status. Histological con?rmation of diagnosis reduced the pos-
otene and smoking, it would help explain why ?-carotene and
sibility of disease misclassi?cation, whereas the population-
total carotenoids, which come from similar sources, were as-
based approach to subject selection facilitated extrapolation of
sociated with a reduced pancreatic cancer risk in this study
our results to the general population.
only among those who never smoked.
Our study is also subject to certain limitations. Because the
The major strengths of our study include its uniqueness, the
assessment of dietary exposure was retrospective, recall bias
large number of pancreatic cancer cases, histological diagnosis
cannot be completely excluded. A prospective cohort ap-

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596
NKONDJOCK ET AL.
TABLE 3
Odds ratio (OR) and 95% CI for pancreatic cancer associated with dietary carotenoids and tobacco use1,2
Quartiles of energy-adjusted carotenoid intakes
P for
Tobacco use
Carotenoid
1
2
3
4
trend
Never smoked
?-Carotene
1.00
1.09 (0.60–1.99)
0.72 (0.41–1.28)
0.57 (0.32–0.99)
0.016
Cases/Controls, n
27/467
27/470
39/432
48/441
Total carotenoids
1.00
1.10 (0.61–2.00)
0.79 (0.45–1.38)
0.58 (0.34–1.00)
0.020
Cases/Controls, n
28/470
28/463
36/433
49/444
Past smokers
?-carotene
1.00
1.24 (0.78–1.97)
0.98 (0.64–1.51)
1.38 (0.86–2.22)
0.44
Cases/Controls, n
50/425
40/451
59/502
40/486
Total carotenoids
1.00
1.07 (0.68–1.70)
0.94 (0.61–1.47)
1.22 (0.76–1.97)
0.62
Cases/Controls, n
49/418
43/458
57/504
41/486
Current smokers
?-Carotene
1.00
0.83 (0.47–1.46)
0.82 (0.47–1.44)
1.61 (0.85–3.04)
0.24
Cases/Controls, n
32/285
36/260
39/248
25/254
Total carotenoids
1.00
0.76 (0.44–1.34)
0.85 (0.49–1.49)
1.70 (0.90–3.23)
0.15
Cases/Controls, n
33/291
37/262
37/246
24/250
1 Values are OR (95% CI).
2 OR and 95% CI from the logistic regression model adjusted for age, sex, province, educational attainment, BMI, folate, and total energy intake.
proach has several advantages when studying associations be-
patterns, smoking, or educational attainment, survivors are
tween nutritional factors and cancer risk. However, because of
still representative of the study population. Consequently,
the relatively low incidence of pancreatic cancer, the largest
selection bias is unlikely to be substantial.
cohort to date examining diet and pancreatic cancer risk
In conclusion, we found a signi?cantly reduced pancreatic
included only 178 pancreatic cancer cases throughout 18 y of
cancer risk with dietary intake of lycopene among men. A
follow-up (27). We could not adjust OR estimates for the
signi?cant inverse association was also observed between pan-
potentially confounding effect of diabetes mellitus and family
creatic cancer risk and both dietary ?-carotene and total
history of pancreatic cancer because this information was not
carotenoid intakes among those who never smoked. As a
collected at baseline. Nevertheless, we expect that diabetes did
whole, our data supported the association of a diet rich in
not confound the association between dietary carotenoids and
vegetables with a reduction in risk of pancreatic cancer. More
pancreatic cancer risk because diet is likely to be an initial risk
studies assessing associations between dietary carotenoids and
factor for both chronic diseases, rather than lying on their
the risk of pancreatic cancer are warranted to better elucidate
causal pathways. In addition, it was suggested that the impor-
the role of diet in the etiology of pancreatic cancer.
tance of diabetes is much reduced if pancreatic cancer cases of
recent onset are excluded (28). In addition, it is unlikely that
ACKNOWLEDGMENTS
the confounding effect of family aggregation of pancreatic
cancer may explain the associations we found because genetic/
The Canadian Cancer Registries Epidemiology Research Group
familial predisposition is relatively rare (29). Moreover,
comprises a Principal Investigator from each of the Provincial Cancer
Registries: B. Paulse, Newfoundland Cancer Foundation; R. Dewar,
con?rmation of a hereditary component is particularly chal-
Nova Scotia Cancer Registry; D. Dryer, Prince Edward Island Cancer
lenging because pancreatic cancer may occur only infre-
Registry; N. Kreiger, Cancer Care Ontario; E. Kliewer, Cancer Care
quently in some of the hereditary cancer syndromes, in
Manitoba; D. Robson. Saskatchewan Cancer Foundation; S. Fin-
accordance with reduced frequency of the deleterious, pre-
cham, Division of Epidemiology, Prevention and Screening, Alberta
disposing mutations (30).
Cancer Board; and N. Le, British Columbia Cancer Agency.
Although the USDA-NCC Carotenoid Database used in
the present analysis represents the most current and compre-
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