National Academy of Sciences
References
461. JAMA 1994 Nov
9;272(18):1413-20
Published erratum appears in JAMA 1995 Feb
22;273(8):622
Dietary carotenoids, vitamins A, C, and E, and advanced
age-related macular
degeneration. Eye Disease Case-Control Study Group.
Seddon JM, Ajani UA, Sperduto RD, Hiller R, Blair N, Burton
TC, Farber MD,
Gragoudas ES, Haller J, Miller DT, et al
Epidemiology Unit, Massachusetts Eye and Ear Infirmary,
Boston 02114.
OBJECTIVE--To evaluate the relationships between dietary
intake of carotenoids and vitamins A, C, and E and the risk
of neovascular age-related macular degeneration (AMD), the
leading cause of irreversible blindness among adults.
DESIGN--The multicenter Eye Disease Case-Control Study.
SETTING-Five ophthalmology centers in the United States.
PATIENTS--A total of 356 case subjects who were diagnosed
with the advanced stage of AMD within 1 year prior to their
enrollment, aged 55 to 80 years, and residing near a
participating clinical center. The 520 control subjects were
from the same geographic areas as case subjects, had other
ocular diseases, and were frequency-matched to cases
according to age and sex. MAIN OUTCOME MEASURES--The relative
risk for AMD was estimated according to dietary indicators of
antioxidant status, controlling for smoking and other risk
factors, by using multiple logistic-regression analyses.
RESULTS--A higher dietary intake of carotenoids was
associated with a lower risk for AMD. Adjusting for other
risk factors for AMD, we found that those in the highest
quintile of carotenoid intake had a 43% lower risk for AMD
compared with those in the lowest quintile (odds ratio, 0.57;
95% confidence interval, 0.35 to 0.92; P for trend = .02).
Among the specific carotenoids, lutein and zeaxanthin, which
are primarily obtained from dark green, leafy vegetables,
were most strongly associated with a reduced risk for AMD (P
for trend = .001). Several food items rich in carotenoids
were inversely associated with AMD. In particular, a higher
frequency of intake of spinach or collard greens was
associated with a substantially lower risk for AMD (P for
trend < .001). The intake of preformed vitamin A (retinol)
was not appreciably related to AMD. Neither vitamin E nor
total vitamin C consumption was associated with a
statistically significant reduced risk for AMD, although a
possibly lower risk for AMD was suggested among those with
higher intake of vitamin C, particularly from foods.
CONCLUSION--Increasing the consumption of foods rich in
certain carotenoids, in particular dark green, leafy
vegetables, may decrease the risk of developing advanced or
exudative AMD, the most visually disabling form of macular
degeneration among older people. These findings support the
need for further studies of this relationship.
462. Cancer Epidemiol
Biomarkers Prev 1994 Oct-Nov;3(7):571-4
Increased plasma level of cholesterol-5 beta,6 beta-epoxide
in endometrial
cancer patients.
Kucuk O, Churley M, Goodman MT, Franke A, Custer L, Wilkens
LR, St Pyrek J
Prevention and Control [O. K., M. C.], Epidemiology [M. T.
G., L. R. W.], and
Molecular Oncology [A. F., L. C.], University of Hawaii,
Honolulu 96813.
Plasma levels of alpha- and beta-isomers of cholesterol-5,
6-epoxides were
quantitated in a pilot study of 9 women with endometrial
cancer and 9 race- and
age-matched control women by isotope dilution gas
chromatography/mass
spectrometry. Endometrial cancer cases had significantly
higher cholesterol-5
beta,6 beta-epoxide levels than the controls (P = 0.01). The
mean plasma
beta-epoxide level was 0.71 0.46 ng/ml for the cases and
0.35 0.25 ng/ml
for the controls. No significant differences were found
between the plasma
alpha-epoxide levels of the cases and the controls. Plasma
levels of various
carotenoids, tocopherols, and ascorbic acid were also
quantitated by high
performance liquid chromatography. An inverse correlation
was present between the plasma levels of cholesterol-5 beta,6
beta-epoxide and cis-lutein/zeaxanthin
(P = 0.01). These data suggest a possible role for
cholesterol-5 beta,6
beta-epoxide as a biomarker of endometrial cancer risk.
Further studies are
warranted to investigate the possible association between
the oxidation products of cholesterol and endometrial cancer
and to determine the interactive role of antioxidants.
463. Circulation 1994
Sep;90(3):1154-61
Serum antioxidants and myocardial infarction. Are low levels
of carotenoids and
alpha-tocopherol risk factors for myocardial
infarction?
Street DA, Comstock GW, Salkeld RM, Schuep W, Klag MJ
Department of Epidemiology, Johns Hopkins University School
of Hygiene and
Public Health, Baltimore, Md.
BACKGROUND: In vitro, animal and epidemiological studies
suggest that
lipoprotein oxidation may play an important role in
atherosclerosis.
Antioxidants may protect against lipoprotein oxidation and
in that way inhibit
atherosclerosis and its clinical sequelae. To investigate
this possibility, we
examined the association between levels of several
antioxidants and myocardial
infarction using serum specimens collected 7 to 14 years
before the onset of
myocardial infarction. METHODS AND RESULTS: A nested
case-control design was used. Cases and control subjects were
selected from the 25,802 persons who had donated 15 mL of
blood in 1974 for a serum bank. Cases comprised 123 persons
with a subsequent first diagnosis of myocardial infarction
who ranged from 23 through 58 years of age in 1974 and who
had had their first diagnosis of myocardial infarction during
1981 to 1988. Two groups of control subjects matched to the
cases for sex and age were selected from donors to the serum
bank, one from those with hospital admissions during the same
period and the other from the total group of donors. Sera
were assayed for four carotenoids (beta-carotene, lycopene,
lutein, and zeaxanthin), alpha-tocopherol, and cholesterol.
Because associations with these serum nutrients showed
similar trends whether based on hospital or community
controls, the two control groups were combined. There was a
significantly increasing risk for subsequent
myocardial infarction with decreasing levels of
beta-carotene in 1974 (P value
for trend, .02) and a suggestive trend with decreasing
levels of lutein (P =
.09). When the results were stratified by smoking status,
the excess risk of
myocardial infarction associated with low serum levels of
carotenoids was
limited to smokers. A protective association with higher
levels of
alpha-tocopherol was suggested only among persons with high
levels of serum
cholesterol. CONCLUSIONS: Low serum levels of carotenoids
were associated with an increased risk of subsequent
myocardial infarction among smokers.
464. Am J Clin Nutr 1994
Apr;59(4):891-5
Effect of smoking on serum nutrient concentrations in
African-American women.
Pamuk ER, Byers T, Coates RJ, Vann JW, Sowell AL, Gunter EW,
Glass D
Division of Nutrition, Centers for Disease Control and
Prevention, Atlanta.
The relationship between current cigarette smoking and
serum concentrations of
vitamins C, E, and A, and of five carotenoids in human serum
were examined in 91
low-income, African-American women. General linear models
were used to adjust geometric mean serum concentrations of
micronutrients for age, dietary and supplement intakes, total
energy intake, alcohol intake, medication use, body mass
index, and serum concentrations of cholesterol and
triglycerides. Among smokers, serum concentrations of
alpha-carotene, beta-carotene, cryptoxanthin, and lycopene
averaged only 71-79% of the concentrations among nonsmokers.
Mean serum concentrations of vitamins C and E and
lutein/zeaxanthin were only slightly lower among smokers
relative to nonsmokers, and current smokers had higher serum
concentrations of vitamin A. Among current smokers, mean
serum concentrations of all five carotenoids decreased with
an increase in the amount smoked. The negative effect of
smoking on serum concentrations of antioxidant carotenoids
may pose a serious health risk in low-income populations
already at higher risk for many chronic diseases.
465. Cancer Epidemiol
Biomarkers Prev 1993 Jul-Aug;2(4):335-9
Serum micronutrients and the subsequent risk of cervical
cancer in a
population-based nested case-control study.
Batieha AM, Armenian HK, Norkus EP, Morris JS, Spate VE,
Comstock GW
Department of Epidemiology, School of Hygiene and Public
Health, Johns Hopkins University, Baltimore, Maryland
21205.
A nested case-control study was conducted in Washington
County, MD, to determine whether low serum micronutrients are
related to the subsequent risk of cervical cancer. Among the
15,161 women who donated blood for future cancer research
during a serum collection campaign in 1974, 18 developed
invasive cervical cancer and 32 developed carcinoma in situ
during the period January 1975 through May 1990. For each of
these 50 cases, two matched controls were selected from the
same cohort. The frozen sera of the cases and their matched
controls were analyzed for a number of nutrients. The mean
serum levels of total carotenoids, alpha-carotene,
beta-carotene, cryptoxanthin, and lycopene were lower among
cases than they were among controls. When examined by
tertiles, the risk of cervical cancer was significantly
higher among women in the lower tertiles of total carotenoids
(odds ratio 2.7; 95% confidence limit, 1.1-6.4),
alpha-carotene (odds ratio, 3.1; 95% confidence limit,
1.3-7.6), and beta-carotene (odds ratio, 3.1; 95% confidence
limit, 1.2-8.1) as compared to women in the upper tertiles
and the trends were statistically significant.
Cryptoxanthin was significantly associated with a lower risk
of cervical cancer
when examined as a continuous variable. Retinol, lutein,
alpha- and
gamma-tocopherol, and selenium were not related to cervical
cancer risk. Smoking was also strongly associated with
cervical cancer. These findings are suggestive of a
protective role for total carotenoids, alpha-carotene and
beta-carotene in cervical carcinogenesis and possibly for
cryptoxanthin and lycopene as well.
466. Cancer Epidemiol
Biomarkers Prev 1993 May-Jun;2(3):183-7
Published erratum appears in Cancer Epidemiol Biomarkers
Prev 1994 Sep;3(6):523 Intake of specific carotenoids and
lung cancer risk.
Le Marchand L, Hankin JH, Kolonel LN, Beecher GR, Wilkens
LR, Zhao LP
Cancer Research Center, University of Hawaii, Honolulu
96813.
Using newly available food composition data for
carotenoids, the authors
reanalyzed a population-based case-control study of diet and
lung cancer
conducted in Hawaii in 1983-1985 (L. Le Marchand et al., J.
Natl. Cancer Inst.,
81158-1164, 1989). The analysis included interviews with 230
men and 102
women with lung cancer and 597 men and 268 women as
controls, frequency-matched to the patients by age and sex. A
previously validated quantitative diet history assessed the
usual intake of foods rich in carotenoids. After adjusting
for
smoking and other covariates, no association was found with
lung cancer risk for dietary lycopene or beta-cryptoxanthin
intake, whereas dose-dependent inverse associations of
comparable magnitude were found for dietary beta-carotene,
alpha-carotene, and lutein. When subjects were
cross-classified by their joint intakes of the latter three
carotenoids, those who had a high intake (> median) for
all three had the lowest risk for lung cancer. In a similar
two-way
interaction analysis, the previously reported inverse
association of lung cancer
with vegetable consumption in these data was found to be
stronger than that with intake of these three carotenoids.
Consistent with our previous findings, this
analysis provides further evidence for a protective effect
of certain carotenoids against lung cancer and for the
greater protection afforded by consuming a variety of
vegetables compared to only foods rich in a particular
carotenoid.
467. Cancer Res 1993 Feb
1;53(3):536-43
Vegetables, fruit, and lung cancer in the Iowa Women's
Health Study.
Steinmetz KA, Potter JD, Folsom AR
Division of Epidemiology, School of Public Health,
University of Minnesota,
Minneapolis 55454-1015.
Previous epidemiological studies have shown an inverse
association between
vegetable and fruit consumption and lung cancer risk; few of
these studies have
been prospective or have focused upon women. In 1986, we
assessed food intake in 41,837 Iowa women, aged 55 to 69 yr,
with a mailed 127-item food frequency questionnaire. After 4
years of follow-up, 179 incident cases of lung cancer were
identified via the Iowa Surveillance, Epidemiology, and End
Results cancer registry. After specific exclusion criteria
were applied, a nested case-control comparison of 138 cases
with 2,814 randomly selected noncases was undertaken.
Intakes, in the upper-most quartile, of 11 vegetable and
fruit groups, as well as of the nutrients beta-carotene and
vitamin C, were explored. High intakes of all vegetables and
fruit, all vegetables, and green leafy vegetables were each
associated with an approximate halving of risk: age-,
smoking-, and
energy-adjusted odds ratios (ORs) were 0.49 (95% confidence
interval,
0.28-0.86), 0.50 (95% confidence interval, 0.29-0.87), and
0.45 (95% confidence
interval, 0.26-0.76), respectively. A lower lung cancer risk
was also seen for
all fruit (adjusted OR = 0.75 for high consumption), high
vitamin C vegetables
and fruit (OR = 0.75), carrots (OR = 0.71), and brocolli (OR
= 0.72) and for the
nutrients beta-carotene (OR = 0.81) and vitamin C (OR =
0.81) (all 95%
confidence intervals included 1.0). Lung cancer risk was
unrelated to
consumption of the three food groups defined as
"high-carotenoid"
(beta-carotene, lutein, and lycopene) and tomatoes. In an
analysis stratified by
histological type of lung cancer, the strongest inverse
associations for
vegetables and fruit were seen for large cell carcinoma.
Analysis by smoking
status showed the inverse associations for most vegetable
and fruit groups with
lung cancer risk to be stronger for exsmokers than for
current smokers. Results
from the stratified analyses must be interpreted with
caution because of the
small number of cases in each stratum.
468. Cancer Res 1993 Feb
1;53(3):536-43
Vegetables, fruit, and lung cancer in the Iowa Women's
Health Study.
Steinmetz KA, Potter JD, Folsom AR
Division of Epidemiology, School of Public Health,
University of Minnesota,
Minneapolis 55454-1015.
Previous epidemiological studies have shown an inverse
association between
vegetable and fruit consumption and lung cancer risk; few of
these studies have
been prospective or have focused upon women. In 1986, we
assessed food intake in 41,837 Iowa women, aged 55 to 69 yr,
with a mailed 127-item food frequency questionnaire. After 4
years of follow-up, 179 incident cases of lung cancer were
identified via the Iowa Surveillance, Epidemiology, and End
Results cancer registry. After specific exclusion criteria
were applied, a nested case-control comparison of 138 cases
with 2,814 randomly selected noncases was undertaken.
Intakes, in the upper-most quartile, of 11 vegetable and
fruit groups, as well as of the nutrients beta-carotene and
vitamin C, were explored. High intakes of all vegetables and
fruit, all vegetables, and green leafy vegetables were each
associated with an approximate halving of risk: age-,
smoking-, and
energy-adjusted odds ratios (ORs) were 0.49 (95% confidence
interval,
0.28-0.86), 0.50 (95% confidence interval, 0.29-0.87), and
0.45 (95% confidence
interval, 0.26-0.76), respectively. A lower lung cancer risk
was also seen for
all fruit (adjusted OR = 0.75 for high consumption), high
vitamin C vegetables
and fruit (OR = 0.75), carrots (OR = 0.71), and brocolli (OR
= 0.72) and for the
nutrients beta-carotene (OR = 0.81) and vitamin C (OR =
0.81) (all 95%
confidence intervals included 1.0). Lung cancer risk was
unrelated to
consumption of the three food groups defined as
"high-carotenoid"
(beta-carotene, lutein, and lycopene) and tomatoes. In an
analysis stratified by
histological type of lung cancer, the strongest inverse
associations for
vegetables and fruit were seen for large cell carcinoma.
Analysis by smoking
status showed the inverse associations for most vegetable
and fruit groups with
lung cancer risk to be stronger for exsmokers than for
current smokers. Results
from the stratified analyses must be interpreted with
caution because of the
small number of cases in each stratum.
469. Cancer Res 1992 Apr 1;52(7
Suppl):2060s-2066s
Does beta-carotene explain why reduced cancer risk is
associated with vegetable and fruit intake?
Ziegler RG, Subar AF, Craft NE, Ursin G, Patterson BH,
Graubard BI
Environmental Epidemiology Branch, National Cancer
Institute, Bethesda, Maryland 20892.
Increased intake of vegetables, fruits, and carotenoids
and elevated blood
levels of beta-carotene are consistently associated with
reduced risk of lung
cancer in epidemiologic studies. Epidemiologic research also
suggests that
carotenoids may reduce the risk of other cancers, although
the evidence is less
extensive and consistent. The simplest explanation is that
beta-carotene is
protective. However, the possible roles of other
carotenoids, other constituents
of vegetables and fruits, and associated dietary patterns
have not been
adequately explored. To evaluate these alternative
hypotheses, we are
undertaking three lines of research. (a) With dietary data
from the 1987
National Health Interview Survey and the 1982-1984
Epidemiologic Follow-up of
the first National Health and Nutrition Examination Study,
we have determined
which food groups and nutrients are highly correlated with
vegetable and fruit
intake. (b) We have developed and characterized a liquid
chromatography method for optimal recovery and resolution of
the common carotenoids in blood,
specifically lutein, zeaxanthin, beta-cryptoxanthin,
lycopene, alpha-carotene,
and beta-carotene. (c) In a population-based case-control
study of lung cancer
in white men in New Jersey, we are assessing whether
estimates of the intake of the individual carotenoids might
produce stronger inverse associations than
estimates of provitamin A carotenoids based on current food
composition tables.
470. Am J Epidemiol 1991 Dec
1;134(11):1347-55
A case-control study of nutrient status and invasive
cervical cancer. II.
Serologic indicators.
Potischman N, Herrero R, Brinton LA, Reeves WC,
Stacewicz-Sapuntzakis M, Jones CJ, Brenes MM, Tenorio F, de
Britton RC, Gaitan E
Environmental Epidemiology Branch, National Cancer
Institute, Bethesda, MD.
A study of 387 cases and 670 controls from four Latin
American countries
evaluated the hypothesis that lower serum levels of eight
micronutrients were
associated with a higher risk of invasive cervical cancer.
The serologic
analyses were restricted to a sample of subjects with stage
I and II disease to
minimize effects of the disease on the serologic markers.
Ninety-four percent of
eligible subjects donated blood samples, which were analyzed
for carotenoids,
retinol, and tocopherols by high-pressure liquid
chromatography. Cases did not
differ significantly from controls in mean serum levels of
retinol,
cryptoxanthin, lycopene, alpha-carotene, lutein, or
alpha-tocopherol. The mean
level of beta-carotene was lower and the mean level of
gamma-tocopherol was
higher among cases as compared with controls. After
adjustment for age, study
site, sexual and reproductive behavior, socioeconomic
status, screening
practices, detection of human papillomavirus types 16/18,
cholesterol, and
triglycerides, a trend of decreasing risk was associated
with higher levels of
beta-carotene (p for trend = 0.05), with the adjusted odds
ratio decreasing to
0.72 for the highest versus the lowest quartile.
beta-Carotene results were
similar by stage of disease, which argues against an effect
of disease
progression on nutrient values. Unexpectedly, increasing
risks were observed as
the level of gamma-tocopherol increased (odds ratio = 2.09;
p for trend = 0.03);
however, levels were higher among stage II cases as compared
with stage I cases, suggesting a metabolic alteration
resulting from the disease process. The
concordance in the strength and direction of the blood and
dietary results,
presented in the accompanying report (Herrero R, Potischman
N, Brinton LA, et
al., American Journal of Epidemiology 1991;134:1335-46),
supports a role for
beta-carotene or foods rich in beta-carotene in the etiology
of cervical cancer.
This study also indicates that simultaneous analysis using
serologic and dietary
nutrient indicators allows better discrimination of the
association.