Dietary protein sources in early adulthood and breast cancer incidence: prospective cohort study
BMJ 2014; 348 doi: http://dx.doi.org/10.1136/bmj.g3437 (Published 10 June 2014) Cite this as: BMJ 2014;348:g3437- Maryam S Farvid, Takemi fellow, and associate professor12,
- Eunyoung Cho, associate professor34,
- Wendy Y Chen, assistant professor45,
- A Heather Eliassen, assistant professor 46,
- Walter C Willett, professor146
- Correspondence to: M S Farvid mfarvid@hsph.harvard.edu
- Accepted 14 May 2014
Abstract
Objective To investigate the association between dietary protein sources in early adulthood and risk of breast cancer.
Design Prospective cohort study.
Setting Health professionals in the United States.
Participants 88 803 premenopausal women from the Nurses’ Health Study II who completed a questionnaire on diet in 1991.
Main outcome measure Incident cases of invasive breast carcinoma, identified through self report and confirmed by pathology report.
Results
We documented 2830 cases of breast cancer during 20 years of follow-up.
Higher intake of total red meat was associated with an increased risk
of breast cancer overall (relative risk 1.22, 95% confidence interval
1.06 to 1.40; Ptrend=0.01, for highest fifth v
lowest fifth of intake). However, higher intakes of poultry, fish, eggs,
legumes, and nuts were not related to breast cancer overall. When the
association was evaluated by menopausal status, higher intake of poultry
was associated with a lower risk of breast cancer in postmenopausal
women (0.73, 0.58 to 0.91; Ptrend=0.02, for highest fifth v lowest fifth of intake) but not in premenopausal women (0.93, 0.78 to 1.11; Ptrend=0.60, for highest fifth v
lowest fifth of intake). In estimating the effects of exchanging
different protein sources, substituting one serving/day of legumes for
one serving/day of red meat was associated with a 15% lower risk of
breast cancer among all women (0.85, 0.73 to 0.98) and a 19% lower risk
among premenopausal women (0.81, 0.66 to 0.99). Also, substituting one
serving/day of poultry for one serving/day of red meat was associated
with a 17% lower risk of breast cancer overall (0.83, 0.72 to 0.96) and a
24% lower risk of postmenopausal breast cancer (0.76, 0.59 to 0.99).
Furthermore, substituting one serving/day of combined legumes, nuts,
poultry, and fish for one serving/day of red meat was associated with a
14% lower risk of breast cancer overall (0.86, 0.78 to 0.94) and
premenopausal breast cancer (0.86, 0.76 to 0.98).
Conclusion
Higher red meat intake in early adulthood may be a risk factor for
breast cancer, and replacing red meat with a combination of legumes,
poultry, nuts and fish may reduce the risk of breast cancer.
Introduction
The potential influence of dietary protein on risk of breast cancer has created considerable scientific attention.1
High protein intake may affect the risk of breast cancer by increasing
the insulin-like growth factor 1 that plays important roles in tissue
growth and tumor progression.1 2
However, foods that are major sources of protein differ widely in their
nutrient profiles and may have different effects on breast cancer risk.
The overall evidence from prospective cohort studies has suggested no
significant association between red meat intake and breast cancer. A
pooled analysis of eight cohort studies found a null association between
intake of red meat and risk of breast cancer.3 Also, a recent review and meta-analysis of prospective cohort studies4 and a recent prospective study5
did not show effects of red meat intake on breast cancer risk. However,
most of the evidence has come from studies that evaluated diet during
midlife and later. In the Nurses’ Health Study II cohort, red meat
intake during early adulthood was associated with an increased risk of
breast cancer in premenopausal women.6
Moreover, in most prospective studies, little relation has been seen
between intakes of other protein rich foods such as fish, poultry, eggs,
legumes, or nuts and risk of breast cancer, but data from early adult
life are also limited.7 8 9 10 11
The
exposures between menarche and first pregnancy may be more important in
the development of breast cancer. Epidemiologic studies of women who
survived the atomic bombing in Hiroshima and Nagasaki and radiation
treatment for Hodgkin’s lymphoma have shown that exposure to radiation
in childhood and early adulthood was associated with subsequent risk of
cancer, but radiation was less strongly related to risk of breast cancer
among women older than 30 years at the time of exposure.12 13 14
Although
breast tumors vary by estrogen and progesterone receptor status, most
previous studies have evaluated the relation between dietary sources of
protein and breast cancer, with limited information on how the cancers
differed by hormone receptor status.5 6 In an early analysis from the Nurses’ Health Study II with 12 years of follow-up,6
we reported a positive association between red meat intake and breast
cancer in premenopausal women, especially tumors with positive hormone
receptors. However, it was not clear whether the positive findings were
due to early age at dietary assessment or the relatively young age of
women at diagnosis of breast cancer. In this updated analysis with
longer follow-up and approximately three times the number of cases of
breast cancer, we investigated the association of total intakes of
unprocessed and processed red meat before menopause with risk of breast
cancer overall and separately among premenopausal and postmenopausal
women. In addition we examined the associations between breast cancer
and other protein rich foods, including poultry, fish, eggs, legumes,
and nuts. Furthermore, we evaluated whether the association between red
meat and breast cancer differs by hormone receptor status.
Methods
Study population
The
Nurses’ Health Study II began in 1989 and is a prospective cohort study
of 116 430 female registered nurses who were 24 to 43 years of age. In
1991, participants were asked to complete a food frequency questionnaire
about usual dietary intake in the past year. A total of 97 813 women
answered the questionnaire. We excluded those who had an implausible
daily energy intake (<2508 or ≥14630 kJ) or left more than 70 food
items blank on the food frequency questionnaire. Of the remaining
95 452, we excluded women who were postmenopausal in 1991. Participants
were also excluded if they had a diagnosis of any cancer except
non-melanoma skin cancer, diabetes, coronary heart disease, or stroke
before returning the 1991 questionnaire, or had missing data on age or
red meat intake. We included 88 803 women in the analysis. The
cumulative response rate among living participants was 95%.
Dietary assessment
Participants
completed a semi-quantitative food frequency questionnaire with
approximately 130 items in 1991, 1995, 1999, 2003, and 2007 about usual
dietary intake and alcohol consumption during the past year (available
at www.channing.harvard.edu/nhs/?page_id=246).
Total red meat items listed on the food frequency questionnaire
included unprocessed red meat (beef, pork, or lamb as a sandwich, pork
as a main dish, beef or lamb as a main dish, and hamburger) and
processed red meat (hot dogs, bacon, and other processed meat such as
sausage, salami, bologna); poultry included chicken and turkey; fish
included tuna, dark meat fish (for example, mackerel, salmon, sardines,
bluefish, swordfish), and other fish; legumes included tofu or soybeans,
string beans, beans, or lentils, and peas or lima beans; and nuts
included peanut, peanut butter, and other nuts. Responses were given for
commonly used portion sizes and nine categories of intake frequency
ranging from “never or less than once per month” to “six or more per
day.”
Food intake during adolescence was measured in
1998 using a 124 item food frequency questionnaire, which was
specifically designed to contain foods that were usually consumed during
the periods from 1960 to 1980 when these women would have been in high
school. Food items included in the food frequency questionnaire for
adolescents and response categories were similar to those in the food
frequency questionnaire for adults.
We calculated
nutrient intakes by multiplying the frequency of consumption of each
item by the nutrient content of the specified portions and then summing
across all items. Nutrient values in foods were obtained from the US
Department of Agriculture, food manufacturers, independent academic
sources, and our own fatty acid analyses of commonly used margarines,
cooking oils, and baked foods.15 16 17
Every four years, the food composition database was updated to account
for changes in the food supply. We calculated the percentage of energy
from total fat by dividing energy intake from total fat by total energy
intake. Using the residuals from the regression of nutrient intake on
total energy intake, we adjusted total iron and heme iron for energy.18 19
We did not adjust food intakes for total energy intake, as the
correlation between individual foods and total energy intake was low.
The
reproducibility and validity of food frequency questionnaires for
measuring individual red meat items have been evaluated in 173 women
from the Nurses’ Health Study. The correlation coefficients for intake
of individual red meat items comparing diet records with the food
frequency questionnaire were mostly higher than 0.5 after correction for
attenuation because of within person variation in diet records.20
Documentation of breast cancer
We
identified new cases of breast cancers from biennial questionnaires.
Then we got permission from women with breast cancer or next of kin for
those who had died to review hospital records and pathology reports.
Deaths in this cohort were reported through family members and the
postal service in response to the follow-up questionnaires or identified
through annual review of the national death index. Medical records were
obtained for 88% of cases in the Nurses’ Health Study II included in
this analysis. More than 98% of self reported breast cancers were
confirmed through review of pathology reports. Therefore we included
self reported cases with missing pathology reports in the analysis. We
excluded cases of carcinoma in situ from the analyses. To determine the
estrogen and progesterone receptor status of the breast cancer we
abstracted information from pathology reports.
Assessment of other variables
From
the biennial Nurses’ Health Study II questionnaires we collected
information on risk factors for breast cancer, including age, height,
weight, family history of breast cancer, history of benign breast
disease, smoking, race, age at menarche, parity, age at first birth,
menopausal status, postmenopausal hormone use, age at menopause, and
oral contraceptive use. All variables except race, height, and age at
menarche were updated to the most recent information before date of
diagnosis, whenever available. We considered women to be premenopausal
if they still had menstrual periods or had hysterectomy with at least
one ovary remaining and were younger than 46 years for smokers or
younger than 48 years for non-smokers. Women were considered as
postmenopausal if they reported permanent cessation of menstrual periods
or had undergone bilateral oophorectomy. We defined women of unknown
menopausal status or who had hysterectomy without bilateral oophorectomy
as postmenopausal if they were 54 years or older for smokers or 56
years or older for non-smokers.21
Statistical analysis
We
calculated person years from the return date of the 1991 questionnaire
until the date of breast cancer diagnosis, death, or end of follow-up (1
June 2011), whichever came first. We used the dietary intake in 1991 in
the primary analysis as this represents the dietary intake in early
adulthood. Women were divided into five categories according to food
group or nutrient intake. We used Cox proportional hazards models,
stratified by age in months and questionnaire year, to estimate relative
risk and 95% confidence intervals. Multivariable models adjusted for
race, family history of breast cancer in mother or sisters, history of
benign breast disease, smoking, height, body mass index, age at
menarche, parity, age at first birth, oral contraceptive use, and
alcohol and energy intakes, and, for postmenopausal women, age at
menopause and hormone use. For all women, we additionally adjusted for
menopausal status. We replaced missing covariate data, which comprised
5.5% of total person years for oral contraceptive use and less than 5%
of total person years for body mass index, smoking, height, age at
menarche, age at menopause, parity, and age at first birth, with the
carried forward method for continuous variables and missing indicator
method for categorical variables.
To best represent long
term effects of food intake on breast carcinogenesis and to minimize
measurement error caused by within person variation, we calculated
premenopausal cumulative averaged intakes of food groups using the 1991,
1995, 1999, 2003, and 2007 dietary data for a sensitivity analysis. To
evaluate the effects of diet during the premenopausal period on risk of
breast cancer, we stopped updating the dietary data when the
participants reported change in menopausal status. We used the median
value of each variable in each fifth as a continuous variable for tests
for trend. We estimated the effect of substituting one serving/day of
poultry, fish, legumes, eggs, or nuts for one serving/day of total red
meat by including simultaneously these food items as well as low fat
dairy products and high fat dairy products as continuous variables in
the multivariable model. The relative risk and the 95% confidence
intervals for the substitution effect were derived from the difference
between the regression coefficients, variances, and covariance.22
We examined effect modification for the association between red meat
and breast cancer risk by other measures of breast cancer risk factors. A
cross product interaction term between each factor and intake of red
meat expressed as a continuous variable was included in the
multivariable model. We used a likelihood ratio test with one degree of
freedom to derive P values for tests for interactions. We also tested
the differential association between total red meat intake and breast
cancer risk by estrogen and progesterone receptor status using Cox
proportional cause specific hazards regression model with a duplication
method for competing risk data. This method permits the estimation of
separate associations of red meat with each of positive estrogen and
progesterone receptors and negative estrogen and progesterone receptors,
and has been used to assess whether red meat intake has statistically
different regression coefficients for different tumor subtype. We used
SAS version 9.3 (SAS Institute, Cary, NC) for all analyses. All P values
are two sided.
Results
During
1 725 419 person years of follow-up of 88 803 premenopausal women, 2830
cases of invasive breast carcinoma were documented (1511 premenopausal
breast cancer, 918 postmenopausal breast cancer, and 401 uncertain
menopausal status) between 1991 and 2011. The average age of the
participants in 1991 was 36.4 (SD 4.6) years (range 26-45 years) and the
average age of breast cancer diagnosis was 45 years in premenopausal
women (range 27-60 years) and 55 years in postmenopausal women (range
39-64 years). Table 1⇓
shows the age adjusted distribution of breast cancer risk factors
according to fifths of total red meat intake. Compared with women who
consumed a lower amount of red meat, women with a higher intake were
more likely to have a larger body mass index, to have higher energy
intake, to smoke, and to have three or more children as well as less
likely to use oral contraceptives and to have a history of benign breast
disease.
Table 1
Age standardized distribution of potential risk factors for breast
cancer according to fifths of total red meat intake in 1991 among women
enrolled in the Nurses’ Health Study II
Among
all women, higher total red meat intake in 1991 was associated with an
increased risk of breast cancer in multivariable analysis (relative risk
1.22, 95% confidence interval 1.06 to 1.40; Ptrend=0.01, for highest fifth v lowest fifth) (table 2⇓).
Similar point estimates were observed among premenopausal and
postmenopausal women, separately, though they did not reach statistical
significance. Among all women, the positive association between total
red meat was still significant after additional adjustment for total fat
intake (for highest v lowest fifth: relative risk 1.20, 1.03 to 1.40; Ptrend=0.04), fruits and vegetables intake (for highest v lowest fifth: 1.19, 1.04 to 1.37, Ptrend=0.03), or heme iron (for highest v lowest fifth: 1.21, 1.04 to 1.41; Ptrend=0.03).
We also controlled for the frequency of having fried foods at home and
away from home, but the results were not appreciably altered (data not
shown). When total red meat intake was modeled as a continuous variable,
each additional serving/day increase in total red meat was associated
with a 13% increase in risk of breast cancer among all women (relative
risk 1.13, 1.04 to 1.22), 12% increase among premenopausal women (1.12,
1.01 to 1.25), and 8% increase among postmenopausal women (1.08, 0.94 to
1.23). Additional adjustment for red meat intake during adolescence did
not appreciably attenuate the relative risk. Among women with dietary
data for both adulthood and adolescence (n=40 644), the relative risk
for one serving/day of total red meat intake during adulthood was 1.20
(1.07 to 1.34) for breast cancer overall and 1.24 (1.07 to 1.44) for
premenopausal breast cancer. After additional adjustment for red meat
intake during adolescence, the relative risk was 1.18 (1.06 to 1.33) for
breast cancer overall and 1.20 (1.03 to 1.40) for premenopausal breast
cancer. In a sensitivity analysis using the cumulative average of
premenopausal intake, similar results have been found (for each
additional serving/day: relative risk among all women 1.12, 1.03 to 1.22
and among premenopausal women 1.15, 1.02 to 1.29).
Table 2
Relative risk for breast cancer according to fifths of dietary sources
of animal protein in 1991 among women in the Nurses’ Health Study II.
Values are relative risks (95% confidence intervals) unless stated
otherwise
Poultry intake in 1991 was associated with a lower risk of postmenopausal breast cancer (highest v lowest fifth: relative risk 0.73, 0.58 to 0.91; Ptrend=0.02) (table 2⇑),
and the estimate was unchanged with adjustment for fat or fruits and
vegetables intakes (data not shown). Also, cumulative average of
premenopausal intake of poultry was associated with a lower risk of
postmenopausal breast cancer: each additional serving/day of poultry was
associated with a 25% lower risk of postmenopausal breast cancer
(relative risk 0.75, 0.58 to 0.98). Neither baseline intakes of poultry,
nor the cumulative average of premenopausal poultry intakes, were
associated with premenopausal risk of breast cancer. Intakes of legumes,
fish, eggs, and nuts were not associated with either premenopausal or
postmenopausal breast cancer (tables 2 and 3⇓).
In age adjusted and multivariable adjusted models, none of the tests
for trend were significant across fifths of total iron and heme iron
intakes in early adulthood and breast cancer incidence in either
premenopausal or postmenopausal women (see supplementary table S1).
Table 3
Relative risk for breast cancer according to fifths of legumes and nuts
intakes in 1991 among women in the Nurses’ Health Study II. Values are
relative risks (95% confidence intervals) unless stated otherwise
Based
on diet in 1991, substituting one serving/day of legumes for one
serving/day of total red meat was associated with a lower risk of breast
cancer among all women (relative risk 0.85, 0.73 to 0.98) and among
premenopausal women (0.81, 0.66 to 0.99; figure⇓).
Replacement of one serving/day of total red meat with one serving/day
of poultry was associated with a lower risk of breast cancer in all
women (0.83, 0.72 to 0.96) and postmenopausal women (0.76, 0.59 to
0.99). Furthermore, substituting one serving/day of combined legumes,
nuts, poultry, and fish for one serving/day of red meat was associated
with a 14% lower risk of breast cancer overall (0.86, 0.78 to 0.94) and a
14% lower risk of premenopausal breast cancer (0.86, 0.76 to 0.98,
figure).
Multivariable
relative risk and 95% confidence intervals for breast cancer associated
with substitution of dietary sources of protein for total red meat
(TRM) among women in Nurses’ Health Study II. Multivariable model was
adjusted for variables in footnote of table 2 as well as total red meat
(continuous), legumes (continuous), nuts (continuous), poultry
(continuous), fish (continuous), eggs (continuous), low fat dairy
(continuous), and high fat dairy (continuous). *This model was adjusted
for variables in footnote of table 2 as well as total red meat
(continuous), sum of legumes, nuts, poultry, and fish intake
(continuous), eggs (continuous), low fat dairy (continuous), and high
fat dairy (continuous)
We had information on
estrogen receptor status for 81% (n=2306) of breast cancers and
progesterone receptor status for 80% (n=2275) of breast cancers.
Supplementary table S2 presents the associations between total red meat
intake and breast cancer risk according to hormone receptor status; data
are presented for both tumors with positive estrogen and progesterone
receptors and tumors with negative estrogen and progesterone receptors.
We did not observe significant heterogeneity between total red meat
intake and tumor status in either premenopausal or postmenopausal breast
cancer (see supplementary table S2).
We also examined
whether the association between intake of red meat and breast cancer
risk differed by levels of risk factors for breast cancer, including
family history of breast cancer, body mass index, oral contraceptive
use, smoking, history of benign breast disease, alcohol intake,
postmenopausal hormone use, age at first birth, and parity. The
association between red meat intake and breast cancer risk was modified
by oral contraceptives. For each serving/day of total red meat, the risk
of breast cancer was 54% higher among women who currently used oral
contraceptives (relative risk 1.54, 1.13 to 2.08) and 11% higher in
women who were former users (1.11, 1.02 to 1.22), with no association in
non-users (1.04, 0.84 to 1.28) (P for interaction=0.007); the
interaction was also significant among premenopausal women (P for
interaction=0.009).
Discussion
We
found that higher consumption of red meat in women during early
adulthood was associated with a higher risk of breast cancer. Adjusting
for animal fat, fruits and vegetables, and heme iron did not appreciably
change the association between red meat intake and breast cancer risk.
Moreover, poultry intake was associated with a lower risk of breast
cancer in postmenopausal women. Although intakes of legumes, fish, eggs,
and nuts were not significantly associated with breast cancer in either
premenopausal or postmenopausal women, substituting legumes or poultry
or the combination of poultry, fish, legumes, and nuts for red meat was
associated with a lower risk of breast cancer. In addition, higher
intakes of total iron or heme iron were not associated with risk of
breast cancer.
Results in relation to other studies
The
evidence from prospective studies concerning a role of red meat intake
during adulthood in risk of breast cancer is not consistent.3 5 7 8
A recent review and meta-analysis of prospective studies on consumption
of unprocessed and processed red meat and breast cancer incidence found
that the intake of the red meat was not independently associated with
increasing breast cancer risk.4
However, most of the results have been derived from diet during midlife
and later, and red meat intake during early adulthood may be more
related to an increased risk of breast cancer. Carcinogenic byproducts
such as heterocyclic amines and polycyclic aromatic hydrocarbons,
created during high temperature cooking of meat; animal fat and heme
iron from red meat; and hormone residues of the exogenous hormones for
growth stimulation in beef cattle are some of the mechanisms that may
explain the positive association between high intake of red meat and
risk of breast cancer.23 24 25 26 27 28
We had only limited information on cooking methods of red meat.
Controlling for the frequency of fried foods at home and away from home
in this analysis did not alter the results. Furthermore, our findings
persisted after adjustment for heme iron or total fat, thus reducing the
possibility that they were due to higher intake of heme iron and fat.
We
found that the risk of breast cancer was lower in women who replaced
red meat with legumes in early adulthood. Legumes contain several
components such as fiber and phytoestrogen, which have been negatively
associated with breast cancer incidence.29 30 The anticarcinogenic effects of beans have been shown in animal models.31
An intervention study reported that substituting a diet high in
vegetable fat and protein for a diet high in animal fat and protein
could reduce the circulating estrogen levels by more than 40%.32
Reduction in insulin, insulin-like growth factor, and inflammatory
biomarkers, or alterations in lipid metabolism are mechanisms that could
explain the inverse association between legumes and risk of breast
cancer.33
We
did not detect any association between breast cancer in premenopausal
women and poultry intake. However, this association was significant for
breast cancer in postmenopausal women. Intake of poultry was not
associated with a lower risk of breast cancer in some other prospective
studies.3 5 11
Poultry contains higher amounts of polyunsaturated fat than does red
meat, and processing and cooking methods for poultry likely differ from
that of red meat. Similar to the findings from recent meta-analysis of
11 prospective cohort studies with over 13 000 breast cancer events and
over 687 000 participants,34
we did not observe a clear association with fish intake. The results of
the Singapore Chinese Health Study indicated that high consumption of
fish (mean intake ≥58.3 g/day) has been inversely associated with breast
cancer in postmenopausal women; this intake was higher than in our
study.10
A
non-linear association between egg intake and breast cancer risk has
been found in the European Prospective Investigation into Cancer and
Nutrition cohort.8
Although egg consumption has been associated with a borderline linear
trend toward increased risk of breast cancer in premenopausal women in
the Nurses’ Health Study,7
we found no evidence that intake of eggs in early adulthood was
associated with breast cancers in premenopausal or postmenopausal women
in the current analysis. The inconsistencies among the cohort study
results may be due to chance or differences in the consumption level.
The median intake of eggs in the highest fourth in our study population
was 0.43 eggs per day, smaller than the two eggs per day that have been
significantly associated with a higher risk of breast cancer in a pooled
analysis of eight cohort studies.3
Limitations and strengths of this study
Potential
limitations need to be considered. Because the participants were
predominantly white, educated US adults, we cannot determine whether our
findings are generalizable to other race or ethnic groups; however,
race/ethnic specific risk factors for breast cancer have not been
documented. Because dietary intake was assessed by food frequency
questionnaires, some degree of measurement error is inevitably present,
and thus to reduce measurement error we used the cumulative average of
multiple measurements in a sensitivity analysis.
Residual
confounders are always of concern in any observational studies.
Although we adjusted for a wide range of potential confounders for
breast cancer, we still could not rule out the possibility that other
unmeasured or inadequately measured factors have confounded the true
association. We indirectly estimated the effects of substitution of
legumes, poultry, and other protein sources for red meat on risk of
breast cancer. Although trials on dietary modification would be ideal to
support these substitutions, trials with sufficiently large sample
sizes, long follow-up, and adequate compliance are not feasible. In
addition, we made multiple comparisons (different food groups and
nutrients, premenopausal and postmenopausal subgroups, and subtype of
tumors) in this analysis, and we cannot exclude the possibility of type I
errors. However, the central finding of an association with red meat
was a prior hypothesis.
The strengths of this study
include the large number of cases, length of follow-up, and ability to
examine subtypes of breast cancers. The detailed prospective and updated
assessments of diet and lifestyle factors allowed adjustment for many
potential confounders. Recall bias would not be present because the
study was strictly prospective and dietary assessment was conducted on
all participants before the diagnosis of breast cancer.
Conclusions
This
analysis supports an association between higher consumption of total
red meat during early adulthood and increased risk of breast cancer that
was not clearly restricted to breast cancers in premenopausal women.
Although the association was not significant in postmenopausal women
alone, this may be due to lower statistical power in that group so we
are not able to say with confidence that there is no association. In the
current study, each serving per day increase in red meat was associated
with a 13% increase in risk of breast cancer. When this relatively
small relative risk is applied to breast cancer, which has a high
lifetime incidence, the absolute number of excess cases attributable to
red meat intake would be substantial, and hence a public health concern.
Moreover, higher consumption of poultry was related to a lower
incidence of breast cancer in postmenopausal women. Consistent with the
American Cancer Society guidelines,35
replacement of unprocessed and processed red meat with legumes and
poultry during early adulthood may help to decrease the risk of breast
cancer. Further study of the relation between diet in early adulthood
and risk of breast cancer is needed.
What is already known on this topic
- Foods that are major sources of animal or vegetable proteins are not consistently associated with risk of breast cancer
- Most of the evidence has been based on diet during midlife and later, and many lines of evidence suggest that some exposures, potentially including dietary factors, may have greater effects on breast carcinogenesis during early adulthood
What this study adds
- Higher consumption of total red meat during early adulthood was associated with an increased risk of breast cancer
- Higher consumption of poultry during early adulthood was related to a lower incidence of breast cancer in postmenopausal women
- Substituting a combination of poultry, fish, legumes, and nuts as protein sources for red meat during early life seems beneficial for the prevention of breast cancer
Notes
Cite this as: BMJ 2014;348:g3437
Footnotes
- We thank the participants and staff of the Nurses’ Health Study II; the following state cancer registries for their help AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY; and the Connecticut Department of Public Health Human Investigations Committee, which approved this study. Certain data used in this publication were obtained from the Department of Public Health.
- Contributors: MSF, EC, WYC, AHE, and WCW designed the research. MSF carried out the analysis and wrote the manuscript. All authors provided critical input in the writing of the manuscript and read and approved the final version of manuscript. MSF and WCW are the guarantors.
- Funding: This study was supported by the National Institutes of Health grant (R01CA050385). The study sponsors were not involved in the study design and collection, analysis, and interpretation of data, or the writing of the article or the decision to submit it for publication. The authors were independent from study sponsors.
- Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years, no other relationships or activities that could appear to have influenced the submitted work.
- Ethical approval: The study protocol (institutional review board No 1999-P-003389) was approved by the institutional review boards of Brigham and Women’s Hospital and Harvard School of Public Health. The completion of the self administered questionnaire was considered to imply informed consent.
- Data sharing: No additional data available.
- Transparency: MSF and WCW affirm that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.
This
is an Open Access article distributed in accordance with the Creative
Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits
others to distribute, remix, adapt, build upon this work
non-commercially, and license their derivative works on different terms,
provided the original work is properly cited and the use is
non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/.
