catechins and epithelial cancer incidence: the Zutphen elderly study.
IC, Hollman PC, Bueno De Mesquita HB, Feskens EJ, Kromhout D.
National Institute of Public Health and the Environment (RIVM), Department
of Chronic Diseases Epidemiology, PO Box 1, NL-3720 BA Bilthoven, The
The flavonoids, a group of more than 4,000
polyphenolic antioxidants, are
potential cancer preventive components of fruits and vegetables. Catechins,
one of the 6 major groups of flavonoids, are present in high concentrations
in tea as well. Our objective was to evaluate the association between intake
of catechins and incidence of epithelial cancers with data from the Zutphen
Elderly Study, a prospective cohort study among 728 men aged 65-84 years in
1985. The average catechin intake at baseline was 72 mg/day (range, 0-355
mg/day). After 10 years of follow-up, 96 incident epithelial cancers were
recorded, including 42 cases of lung cancer. After multivariate adjustment,
catechin intake was not associated with epithelial cancer (risk ratio [RR]
from lowest to highest tertile: 1.00, 0.75, 0.94; p for trend: 0.82), or
lung cancer (RR from lowest to highest tertile: 1.00, 0.72, 0.92; p for
trend: 0.80). Catechins not from tea
were borderline significantly inversely associated with lung cancer
incidence (RR and 95% confidence interval [CI] for a 7.5-mg increase
in intake: 0.66, 0.42-1.05), whereas catechins from tea were not.
Catechins from apple, the major
source of non-tea catechins, were also related to lung cancer incidence
(RR and 95% CI for a 7.5-mg catechin increase: 0.67, 0.38-1.17). Because
tea, the major catechin source in this population, was not associated with
cancer risk, it seems unlikely that catechins are responsible for the
observed inverse trend between non-tea catechins and lung cancer incidence.
However, differences in bioavailability of the various catechins may play a
role; effects on individual cancer sites cannot be excluded and merit
further investigation. Copyright 2001 Wiley-Liss, Inc.
PMID: 11291060 [PubMed - indexed for MEDLINE]
Journal of the
National Cancer Institute, Vol. 92, No. 2, 154-160, January 19, 2000
Marchand, Suzanne P. Murphy, Jean H. Hankin, Lynne R. Wilkens, Laurence N.
Etiology Program, Cancer Research Center of Hawaii, University of Hawaii,
Loïc Le Marchand, M.D., Ph.D., Etiology Program, Cancer Research Center of
Hawaii, University of Hawaii, 1236 Lauhala St., Suite 407, Honolulu, HI
96813 (e-mail: email@example.com).
BACKGROUND: To investigate
the possible relationship betweenintake of flavonoids—powerful
dietary antioxidants thatmay also inhibit P450 enzymes—and lung
cancer risk, weconducted a population-based, case-control study
in Hawaii.METHODS: An in-person interview assessed smoking
history andusual intake of 242 food items for 582 patients with
incidentlung cancer and 582 age-, sex-, and ethnicity-matched
controlsubjects. Subjects who donated a blood sample were
genotypedfor the P450 enzyme variant allele CYP1A1*2 by use of a
polymerasechain reaction-based method. Logistic regression
analysis was usedto compute odds ratios (ORs) and 95% confidence
intervals (CIs).All P values are two-sided. RESULTS:
After adjusting for smokingand intakes of saturated fat and
ß-carotene, we found
statistically significant inverse associations between lung
cancer risk and the main food sources of the flavonoids quercetin
(onions and apples) and naringin (white grapefruit). The lungcancer OR for the highest compared with the lowest quartile
of intake was 0.5 (95% CI = 0.3-0.9) for onions (P for trend= .001) and 0.6 (95% CI = 0.4-1.0)
for apples(P for
trend =.03). The OR for the highest compared with the lowest
tertileof intake for white grapefruit was 0.5 (95% CI = 0.2-0.9)
(Pfor trend = .02).
No association was found for
important foodsources of other flavonoids. Using
published food-compositiondata for flavonoids, we found an
inverse association betweenintake of quercetin and risk of lung
cancer (P for trend = .07)that appears consistent with
associations for its food sources.The effect of onions was
particularly strong against squamouscell carcinoma (a cell type
specifically associated with CYP1A1*2in our study) and was
modified by the CYP1A1 genotype, suggestingthat CYP1A1 may play
a role in this association. CONCLUSION:If replicated,
particularly in prospective studies,
these findingswould suggest that foods rich in certain
flavonoids may protect againstcertain forms of lung cancer
and that decreased bioactivationof carcinogens by
inhibition of CYP1A1 should be explored asunderlying mechanisms.
of Clinical Nutrition, Vol. 76, No. 3, 560-568, September 2002
Paul Knekt, Jorma Kumpulainen, Ritva Järvinen, Harri Rissanen, Markku
Heliövaara, Antti Reunanen, Timo Hakulinen and Arpo Aromaa
Background:Flavonoids are effective
antioxidants and may protectagainst several chronic diseases.
The association between flavonoid intake and riskof several
chronic diseases was studied.
Design: The total dietary intakes of 10 054 men and women duringthe year preceding the baseline examination were determined
with a dietary history method. Flavonoid intakes were estimated,
mainly on the basis of the flavonoid concentrations in Finnish
foods. The incident cases of the diseases considered were identifiedfrom different national public health registers.
Persons with higher quercetin intakes had lower mortalityfrom
ischemic heart disease. The relative risk (RR) betweenthe
highest and lowest quartiles was 0.79 (95% CI: 0.63, 0.99:P
for trend = 0.02). The incidence of cerebrovascular diseasewas
lower at higher kaempferol (0.70; 0.56, 0.86; P = 0.003),
naringenin (0.79; 0.64, 0.98; P = 0.06), and hesperetin (0.80;0.64, 0.99; P = 0.008) intakes.
Men with higher quercetin
intakeshad a lower lung cancer incidence (0.42; 0.25, 0.72; P
= 0.001),and men with higher myricetin intakes had a lower
prostate cancerrisk (0.43; 0.22, 0.86; P = 0.002). Asthma
incidence was lowerat higher quercetin (0.76; 0.56, 1.01; P
= 0.005), naringenin(0.69; 0.50, 0.94; P = 0.06), and
hesperetin (0.64; 0.46, 0.88;P = 0.03) intakes. A trend toward a reduction in risk
of type2 diabetes was associated with higher quercetin
(0.81; 0.64,1.02; P = 0.07) and myricetin (0.79; 0.62,
1.00; P = 0.07) intakes.
The risk of some chronic diseases may be lower athigher dietary
Department of Food Science and Institute of Comparative and Environmental
Toxicology, Cornell University, Ithaca, New York 14853-7201 USA. RL23@cornell.edu
Several studies have specifically linked apple consumption
with a reduced risk for cancer,
especially lung cancer. In the Nurses' Health Study and the Health
Professionals' Follow-up Study, involving over 77,000 women and 47, 000 men,
fruit and vegetable intake was associated with a
21% reduced risk in lung cancer risk
in women, but this association was not seen in men. Very few of the
individual fruits and vegetables examined had a significant effect on lung
cancer risk in women, however apples
were one of the individual fruits associated with a decreased risk in lung
cancer. Women who consumed at least one serving per day of apples and
pears had a reduced risk of lung cancer. Of the men involved, there was no
association seen between any individual fruit or vegetable and lung cancer
In a case control study in Hawaii, it was found that
apple and onion intake was
associated with a reduced risk of lung cancer in both males and females.
Smoking history and food intake was assessed for 582 patients with lung
cancer and 582 control subjects without lung cancer.
There was a 40–50% decreased risk in
lung cancer in participants with the highest intake of apples,
onions, and white grapefruit when compared to those who consumed the lowest
amount of these fruits. The decreased risk in lung cancer was seen in both
men and women and in almost all ethnic groups. No associations were seen
with red wine, black tea or green tea. Both onions and apples are high in
flavonoids, especially quercetin and quercetin conjugates. Le Marchand et
al.found an inverse association between lung cancer and quercetin intake
although the trend was not statistically significant. Interestingly, the
inverse association seen between
apple and onion intake and lung cancer were stronger for squamous
cell carcinomas than for adenocarcinomas.
In a Finnish study involving 10,000 men and women and a
24-year follow-up, a strong inverse
association was seen between flavonoid intake and lung cancer
development. In the sampled population, the mean flavonoid intake was 4.0 mg
per day, and 95% of the total flavonoid intake was quercetin. Apples and
onions together provided 64% of all flavonoid intake. The reduced risk of
lung cancer associated with increased flavonoid consumption was especially
strong in younger people and in nonsmokers.
Apples were the only specific foods
that were inversely related to lung cancer risk. Since apples were
the main source of flavonoids in the Finnish population, it was concluded
that the flavonoids from apples were most likely responsible for the
decreased risk in lung cancer.
The relationship of dietary catechins and epithelial cancer
was examined in 728 men (aged 65–84) as part of the Zutphen Elderly Study.
Tea, a naturally high source of catechins, contributed 87% of the total
catechin intake in this study, while apples contributed 8.0% of catechin
consumption. It was found that total catechin and tea consumption did not
have an effect on lung cancer, but apple consumption was associated with decreased epithelial lung cancer
incidence. This supported the findings of the previous studies
discussed, where apples were
significantly inversely associated with lung cancer, and may suggest
that catechins alone do not play have a effect against lung cancers. Other
data from the Zutphen Elderly study showed an inverse association between
fruit and vegetable flavonoids and total cancer incidence and tumors of the
alimentary and respiratory tract. Again, tea flavonoids were not associated
with a decrease in cancer risk.