Jump to content
RemedySpot.com

Vegetable and fruit goodies versus breast cancer

Rate this topic


Guest guest

Recommended Posts

Hi All,

It seems to me to be that the pdf-available paper below is telling

us to eat our fruit and vegetables to avoid breast

cancer for the ladies.

BMI was apparently not a factor and was controlled for.

Not only, as stated in the abstract, was the nodal

spread form of the cancers more susceptible to association

with less alpha-carotene, the differentiated tumor

cells were more susceptible. For the odds ratio of

breast cancer with differentiated cells, the values

were well differentiated, 1.45; moderately differentiated,

0.74; and poorly differentiated, 0.40. This was when the

highest versus lowest quintile of alpha-carotene was

examined.

Lycopene and beta-cryptoxanthin not

being associated with breast cancer

reduced the total carotenoid relative risk.

Retinol had a highest versus lowest quintile odds

ratio of 0.78.

These values for alpha- and gamma-tocopherols

were 0.79 and 0.96, respectively. These values, as

for those of lycopene and retinol, were not significant

statistically.

I believe, that the bottom line is eat your vegetables.

The results fail to match the epidemiological studies

showing a five-fold variation of breast cancer in

different countries. More studies are needed, as they?

Tamimi RM, Hankinson SE, Campos H, Spiegelman D, Zhang S, Colditz

GA,

Willett WC, Hunter DJ.

Plasma Carotenoids, Retinol, and Tocopherols and Risk of Breast

Cancer.

Am J Epidemiol. 2005 Jan 15;161(2):153-160.

PMID: 15632265 [PubMed - as supplied by publisher]

The roles of carotenoids, retinol, and tocopherols in breast

cancer etiology

have been inconclusive. The authors prospectively assessed the

relations between

plasma alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene,

lutein/zeaxanthin, retinol, alpha-tocopherol, and gamma-tocopherol

and breast

cancer risk by conducting a nested case-control study using plasma

collected

from women enrolled in the Nurses' Health Study. A total of 969 cases

of breast

cancer diagnosed after blood draw and prior to June 1, 1998, were

individually

matched to controls. The multivariate risk of breast cancer was 25-

35% less for

women with the highest quintile compared with that for women with the

lowest

quintile of alpha-carotene (odds ratio (OR) = 0.64, 95% confidence

interval

(CI): 0.47, 0.88; p(trend) = 0.01), beta-carotene (OR = 0.73, 95% CI:

0.53,

1.02; p(trend) = 0.01), lutein/zeaxanthin (OR = 0.74, 95% CI: 0.55,

1.01;

p(trend) = 0.04), and total carotenoids (OR = 0.76, 95% CI: 0.55,

1.05; p(trend)

= 0.05). The inverse association observed with alpha-carotene and

breast cancer

was greater for invasive cancers with nodal metastasis. The authors

conclude

that some carotenoids are inversely associated with breast cancer.

Although the

association was strongest for alpha-carotene, the high degree of

collinearity

among plasma carotenoids limits our ability to conclude that this

association is

specific to any individual carotenoid.

Incidence rates for breast cancer vary by more than five-fold

worldwide, suggesting that environmental and lifestyle

factors are important in the etiology of breast cancer (1).

Migration studies indicate that offspring of women moving

from countries of low incidence to countries of high inci-dence

acquire the high breast cancer rates of the new country

(2, 3). Such evidence has motivated research on diet and

breast cancer.

The relation of vegetable consumption to risk of breast

cancer has been investigated in numerous epidemiologic

studies, with inconsistent results. The majority of case-control

studies have found an inverse association (4–10),

while cohort studies report more modest and null associa-

tions (11–16). Fruits and vegetables contain bioactive

substances including carotenoids, which may exhibit anti-carcinogenic

effects (17).

... MATERIALS AND METHODS

Study design and population

The Nurses' Health Study started in 1976, when 121,700

US registered nurses between the ages of 30 and 55 years

returned an initial questionnaire. Every 2 years, information

on reproductive variables, cigarette smoking, postmeno-pausal

hormone use, and dietary information (in 1980, 1984,

1986, 1990, 1994, and 1998) was collected. Incident breast

cancer cases were identified through self-report and were

confirmed by medical record review. Histopathologic char-acteristics

of breast tumors were obtained from medical

records when available. Between 1989 and 1990, blood

samples were collected from 32,826 women. Blood samples

were returned within 26 hours of being drawn; immediately

centrifuged; aliquoted into plasma, red blood cells, and buffy

coat fractions; and stored in liquid nitrogen freezers main-tained

at –130 °C or colder. Follow-up for this subcohort has

been greater than 96 percent for all questionnaire cycles.

This study was approved by the Committee on Human

Subjects at Brigham and Women's Hospital.

Eligible cases in this study consisted of women with

pathologically confirmed, incident invasive and in situ breast

cancer from the subcohort of women who returned a blood

sample and were diagnosed by June 1, 1998. Cases were

excluded if they had any other prior cancer diagnosis except

for nonmelanoma skin cancer. Controls were randomly

selected from the subcohort of women who returned a blood

sample and never reported a diagnosis of cancer (except for

nonmelanoma skin cancer) up to and including the 2-year

interval during which the case was diagnosed. Controls were

matched to cases on year of birth, menopausal status, post-menopausal

hormone use, and time of day, month, and

fasting status at the time of blood draw. Although blood

draw characteristics are unlikely to confound the plasma

micronutrient-breast cancer relation, matching on these

characteristics was necessary for analyses involving other

plasma biomarkers in this nested case-control study. There

were 974 eligible cases and 973 controls with plasma micro-nutrient

data. Because of the following laboratory issues, a

total of nine samples were left unmatched and were dropped

from the matched analyses: six lost during extraction, two

not received by the laboratory, and one with invalid data

possibly due to oxidation. This nested case-control study

consists of 969 matched pairs for which plasma carotenoids,

retinol, and tocopherols were prospectively collected.

... RESULTS

The mean age of women in this study was 57 (standard

deviation, 7) years, with a range from 43 to 70 years. There

were 418 (cases = 206) premenopausal and 1,329 (cases =

666) postmenopausal women at blood draw, with mean ages

of 48.5 (standard deviation, 3) years and 61 (standard devia-tion,

5) years, respectively. Blood samples were collected

from 4 months to 9 years prior to diagnosis (median = 4

years). Cases and controls had the same mean body mass

index at blood draw (25 kg/m 2 ). Compared with controls,

cases had nonsignificantly earlier age at menarche (12.5 vs.

12.6 years), lower mean parity (2.89 vs. 2.97), and older

mean age at first birth (25.1 vs. 24.9 years) among parous

women. Cases had a later mean age of menopause (48.2 vs.

47.7 years, p = 0.01), higher prevalence of family history of

breast cancer (21.0 vs. 13.6 percent, p = 0.001), and more

frequent history of benign breast disease (64.6 vs. 52.5

percent, p = 0.001) compared with controls.

The median values and range of plasma micronutrient

concentrations are presented in table 1. For all of the micro-

nutrients

assayed, median concentrations were higher in the

controls compared with the cases, although none of the

differences was statistically different.

In conditional logistic regression analyses, significant

inverse associations were observed between alpha-carotene

(linear p trend = 0.03) and beta--carotene (linear p trend = 0.02) and

risk of breast cancer (table 2), although the inverse trends

were primarily due to lower odds ratios in the highest quin-tiles

(alpha-carotene: odds ratio (OR) = 0.75, 95 percent confi-dence

interval (CI): 0.56, 1.00; beta--carotene: OR = 0.74, 95

percent CI: 0.56, 1.00). After adjustment for breast cancer

risk factors, these inverse trends remained significant.

Women with the highest quintile of alpha-carotene had 35

percent lower risk of breast cancer compared with women

with the lowest quintile (OR = 0.64, 95 percent CI: 0.47,

0.88). Women with the highest quintile of lutein/zeaxanthin

(OR = 0.74, 95 percent CI: 0.55, 1.01; linear p trend = 0.04) and

total carotenoids (OR = 0.76, 95 percent CI: 0.55, 1.05;

linear p trend = 0.05) had an approximately 25 percent lower

risk of breast cancer compared with women with the lowest

quintile.

Upon adjustment for alpha-carotene, inverse associations with

breast cancer observed with respect to the highest quintiles

of beta--carotene and lutein/zeaxanthin were attenuated, and the

inverse trends were abolished. The odds ratio comparing the

highest quintile of alpha-carotene with the lowest remained

unchanged after mutual adjustment for all of the other nutri-

tional factors, although the confidence interval did include

one (OR = 0.62, 95 percent CI: 0.38, 1.02).

Plasma folate is considered a possible protective factor for

breast cancer (40) and, thus, a potential confounder of the

micronutrient-breast cancer relation. Plasma folate levels

were available for cases diagnosed through June 1, 1996, and

their matched controls. Adjustment for plasma folate levels

resulted in no appreciable change in relative risks for the

carotenoids and tocopherols. Because vitamin E and most

carotenoids are transported in the blood by lipoproteins,

accounting for cholesterol level in the analysis is thought to

provide results unconfounded by blood lipid concentrations

(41). Information on serum cholesterol levels was available

on cases diagnosed through June 1, 1996, and their matched

controls. Inclusion of total cholesterol in multivariate models

resulted in no appreciable difference in odds ratios, and it

was not included in the final models.

Studies of dietary intake of carotenoids, retinol, and

tocopherol and breast cancer suggested that the effect of

these nutritional factors on breast cancer risk differs

according to menopausal status and may be more

pronounced among premenopausal women (42). In this

nested case-control study, there were only 102 premeno-pausal

breast cancer cases, and we were underpowered to

draw any conclusions regarding these micronutrients and

breast cancer risk in these women. Multivariate comparisons

of highest with lowest quintiles of plasma nutrients among

only premenopausal women did not suggest a more

pronounced effect on breast cancer risk. Statistical tests of

interaction revealed that the associations between plasma

nutrients and breast cancer were not statistically different for

premenopausal women compared with postmenopausal

women; therefore, the analyses are not stratified by meno-pausal

status.

To assess if preclinical disease may have affected plasma

micronutrient levels (23), we excluded 161 cases diagnosed

within 2 years of the date of blood collection and their

matched controls. Multivariate results were essentially

unchanged (e.g., comparison of the top quintile with the

bottom: alpha-carotene: OR = 0.62, 95 percent CI: 0.43, 0. 88;

linear p trend = 0.009; beta--carotene: OR = 0.74, 95 percent CI:

0.52, 1.07; linear p trend = 0.02).

When analyses were limited to invasive breast cancer

cases only (n = 776) and their matched controls, multivariate

risks for women with the highest quintile compared with

those with the lowest quintile were 0.64 (95 percent CI: 0.45,

0.93; linear p trend = 0.01) for alpha-carotene and 0.72 (95 percent

CI: 0.50, 1.05; linear p trend = 0.03) for beta--carotene.

Exogenous factors that contribute to oxidative stress in

populations include smoking (43) and alcohol consumption

(18). Individuals exposed to high levels of oxidative stress

may benefit to a greater extent by increased plasma levels of

antioxidants. There was weak evidence that smoking may

modify the risk of breast cancer associated with plasma alpha-carotene

(test for interaction: p = 0.10 (LRT ord )). In multi-variate

analyses, alpha-carotene was inversely associated with

breast cancer among never smokers (OR = 0.5, 95 percent

CI: 0.3, 0.8; linear p trend = 0.01) and past smokers (OR = 0.6,

95 percent CI: 0.3, 0.9; linear p trend = 0.005) but not among

current smokers (OR = 0.9, 95 percent CI: 0.3, 2.6; linear

p trend = 0.30).

An increased risk of breast cancer associated with drinking

six or more alcoholic drinks per week tended to be restricted

to women with the lowest quintiles of plasma micronutri-ents,

although lutein/zeaxanthin was the only one exhibiting

a significant inverse trend in risk among moderate drinkers

(test for interaction: p = 0.06 (LRT ord ); linear p trend = 0.03).

Among women with the lowest quintile of lutein/zeaxanthin,

those who consumed six or more drinks per week had a 60

percent increased risk of developing breast cancer compared

with women who drank less (OR = 1.6, 95 percent CI: 0.8,

3.1).

Some carotenoids and vitamin E may also inhibit prolifer-ation

and tumor progression (23), and oxidative stress may

be associated with metastasis (44). alpha-carotene (linear p trend =

0.002) (table 3), beta--carotene (linear p trend = 0.002), retinol

(linear p trend = 0.03), and a -tocopherol (linear p trend = 0.01)

levels were associated with a significant decreased risk of

breast cancer with nodal metastasis. In multivariate analyses,

women with the highest quintile of alpha-carotene (OR = 0.39,

95 percent CI: 0.22, 0.71) (table 3), beta--carotene (OR = 0.45,

95 percent CI: 0.24, 0.82), and a -tocopherol (OR = 0.53, 95

percent CI: 0.30, 0.93) were more than 50 percent less likely

to have breast cancer with nodal metastases compared with

women with the lowest. In comparison, the nutritional

factors were not significantly associated with risk of invasive

breast cancer with no nodal metastases. The associations

between alpha-carotene (LRT, p = 0.02), beta--carotene (LRT, p =

0.05), and a -tocopherol (LRT, p = 0.03) and breast cancer

risk were different for node-positive cancers compared with

node-negative cancers. Odds ratios for the association

between these micronutrients and invasive cancers involving

metastasis were similar when the outcome was restricted to

breast cancer metastasis with four or more nodes.

In addition, we investigated the relation of alpha-carotene with

pathohistologic characteristics of breast cancer tumors in

multivariate analyses. alpha-carotene was not associated with

tumors characterized as well differentiated, but it was

marginally associated with moderately differentiated tumors

and significantly associated with poorly differentiated

tumors (table 3). The inverse association with alpha-carotene

was apparent for estrogen receptor-positive and -negative

tumors (table 3).

In Western populations, the primary source of alpha-carotene

in the diet is carrots. In this study, carrot consumption was

marginally associated with a decreased risk of breast cancer.

Women consuming carrots on average at least once a day

had a 35 percent decreased risk of breast cancer compared

with women who consumed carrots less than once a month

(multivariate OR = 0.63, 95 percent CI: 0.34, 1.15; linear

p trend = 0.03).

DISCUSSION

To date, this is the largest study to prospectively evaluate

the major plasma carotenoids, tocopherols, and retinol with

respect to breast cancer risk. We observed a 35 percent

reduced risk of breast cancer for women with the highest

quintile of alpha-carotene. In addition, there was evidence that

alpha-carotene had a more pronounced inverse association with

breast cancers with nodal metastasis.

Early studies, which focused on plasma beta--carotene,

retinol, and breast cancer, have been largely inconclusive

(25–29). More recently, three studies have prospectively

evaluated other carotenoids and tocopherols in relation to

breast cancer risk (31, 32, 45). Dorgan et al. (45), reporting

on 105 cases, found a significant inverse association with

lycopene only. In contrast, Toniolo et al. (32), reporting on

270 cases, found no inverse relation with lycopene levels but

found significant inverse associations for alpha-carotene, beta--

carotene,

beta--cryptoxanthin, lutein, and total carotenoids. Sato

et al. (31) reported results for two separate blood donation

cohorts whose results were different from one another. In

one cohort comprising 244 cases, beta--carotene, lycopene, and

total carotenoids were inversely associated with breast

cancer, yet these associations were not observed in the

second cohort comprising 115 cases.

This study was able to assess factors that may modify the

relation between plasma micronutrients and breast cancer.

Smoking and alcohol consumption are two environmental

factors believed to contribute to oxidative stress. There was

evidence that smoking status may modify the association

between plasma alpha-carotene and breast cancer. Contrary to

our a priori hypothesis, the results suggest that the inverse

association observed between alpha-carotene and breast cancer

is limited to former and never smokers.

There was also evidence that the lutein/zeaxanthin relation

with breast cancer may differ according to alcohol consump-tion.

Consumption of alcohol is considered a well-estab-lished,

yet modest risk factor for breast cancer (46). Our data

suggest that the observed increased risk of breast cancer

associated with consuming high levels of alcohol may be

limited to women with low levels of lutein/zeaxanthin.

Zhang et al. (42) observed an interaction between alcohol

consumption and lutein/zeaxanthin among premenopausal

women in this cohort. A controlled feeding study in

premenopausal women reported significantly lower plasma

concentrations of lutein/zeaxanthin when participants

consumed high levels of alcohol. In addition, they observed

slightly increased levels of anhydrolutein, an oxidative

metabolite of this carotenoid (47). Lutein/zeaxanthin may

have antioxidant properties specific to reactive oxygen

species induced by alcohol metabolism, and women

consuming high levels of alcohol may therefore have higher

requirements for lutein/zeaxanthin.

This is the first study to prospectively assess the relation

between plasma carotenoids, retinol, and tocopherols and

breast cancer nodal metastasis at diagnosis. Increased DNA

damage associated with reactive oxygen species has been

reported with metastatic breast cancer DNA compared with

nonmetastatic tumor DNA, suggesting that oxidative stress

enhances the cells' ability to metastasize (48). Previously, in

vitro studies have demonstrated that carotenoids are capable

of reducing proliferation in a number of cancer cell lines

(23), including breast cancer lines (49). Results from this

study suggest that alpha-carotene may be involved in the preven-tion

of nodal metastases.

Previous analyses in the full cohort of the Nurses' Health

Study addressed the role of dietary intake of carotenoids and

risk of breast cancer. Zhang et al. (42) reported inverse asso-

ciations

between the intake of carotenoids, primarily beta--caro-tene

and lutein/zeaxanthin, and risk of breast cancer in

premenopausal women but not among postmenopausal

women. In this nested case-control study, we had few

premenopausal women (n of cases = 102), but there was no

evidence that carotenoids were associated with a decreased

risk of breast cancer.

In contrast, we observed an inverse association of carot-enoids

and breast cancer among postmenopausal women,

while the intake data do not support such an association.

Interestingly, in the full cohort of postmenopausal women,

carrot consumption was inversely associated with breast

cancer risk. The correlation between carrot consumption and

alpha-carotene index is 0.9, suggesting that the discrepancy in

the alpha-carotene index (based on quintiles) and carrot

consumption analysis (based on servings) may be due to a

washing out of the association when quintiles of dietary

index are used as the exposure. If women with the very

highest servings of carrot consumption are the individuals

with the decreased risk of breast cancer, the inverse associa-tion

may not be apparent when these women are forced into

the same quintile category with women consuming less alpha-carotene.

One limitation of this study is that there is only one blood

sample from which to assess micronutrient levels. There is

evidence to suggest that a single sample is adequately repre-sentative

of an individual's long-term exposure. Toniolo et

al. (32) reported intraclass correlations between a single

measurement and average concentrations of carotenoids

over a 3-year period that ranged from 0.63 to 0.85. In addi-tion,

the nutrients assayed are lipid soluble, and the long-term

reproducibility from other studies is good, suggesting

that these measures provide reasonable consistency over

time. Variation that may occur will likely be random and

would result in an attenuation of the true relation (50).

With any observational study, there is potential for

residual and unmeasured confounding. The analyses

presented have controlled for all major breast cancer risk

factors. In addition, we were able to adjust for the

confounding effects of other plasma nutrients in an effort to

ascertain independent nutrient effects. It is still possible that

other nutritional factors yet unidentified or dietary patterns

may be confounding this relation.

Breast cancer is an important public health concern. To

date, there is little information about modifiable risk factors.

Micronutrients, specifically carotenoids, exhibit a great deal

of interindividual variation in their absorption, metabolism,

and excretion (51, 52). Therefore, plasma levels of micronu-trients

may give a more accurate approximation of the

amount available to target tissues than intake estimates.

These results suggest that plasma levels of alpha- or beta--carotene

may play a role in reducing breast cancer risk although,

because of the high degree of collinearity between the

plasma carotenoids, we have limited ability to conclude that

the observed association is specific for alpha-carotene. Further

studies are necessary to confirm the inverse associations

observed between alpha-carotene and breast cancer risk and

nodal metastases and the potential interactions observed

between plasma carotenoids and smoking and alcohol

consumption.

Cheers, Alan Pater, PhD; 4849 Swanson St., Port Alberni, BC, V9Y 6M7;

phone: 250 724-0596; email: old542000@...

Link to comment
Share on other sites

Join the conversation

You are posting as a guest. If you have an account, sign in now to post with your account.
Note: Your post will require moderator approval before it will be visible.

Guest
Reply to this topic...

×   Pasted as rich text.   Paste as plain text instead

  Only 75 emoji are allowed.

×   Your link has been automatically embedded.   Display as a link instead

×   Your previous content has been restored.   Clear editor

×   You cannot paste images directly. Upload or insert images from URL.

Loading...
×
×
  • Create New...