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EPIDEMIOLOGY
Red and processed meat intake and risk of breast cancer:
a meta-analysis of prospective studies
Jingyu Guo
1
•Wei Wei
1
•Lixing Zhan
1,2
Received: 30 January 2015 / Accepted: 9 April 2015 / Published online: 19 April 2015
ÓSpringer Science+Business Media New York 2015
Abstract Epidemiological studies regarding the asso-
ciation between red and processed meat intake and the risk
of breast cancer have yielded inconsistent results. There-
fore, we conducted an updated and comprehensive meta-
analysis which included 14 prospective studies to evaluate
the association of red and processed meat intake with
breast cancer risk. Relevant prospective cohort studies
were identified by searching PubMed through October 31,
2014, and by reviewing the reference lists of retrieved ar-
ticles. Study-specific relative risk (RR) estimates were
pooled using a random-effects model. Fourteen prospective
studies on red meat (involving 31,552 cases) and 12
prospective studies on processed meat were included in the
meta-analysis. The summary RRs (95 % CI) of breast
cancer for the highest versus the lowest categories were
1.10 (1.02, 1.19) for red meat, and 1.08 (1.01, 1.15) for
processed meat. The estimated summary RRs (95 % CI)
were 1.11 (1.05, 1.16) for an increase of 120 g/day of red
meat, and 1.09 (1.03, 1.16) for an increase of 50 g/day of
processed meat. Our findings indicate that increased intake
of red and processed meat is associated with an increased
risk of breast cancer. Further research with well-designed
cohort or interventional studies is needed to confirm the
association.
Keywords Red meat Processed meat Prospective
studies Meta-analysis Breast cancer
Introduction
Breast cancer is the most common cancer in women
worldwide. It is also the major cause of death from cancer
among women globally [1]. It is reported that one in eight
U.S. women (about 12.5 %) will be diagnosed with breast
cancer in her lifetime [2]. In 2014, about 232,340 new
cases of invasive breast cancer will be diagnosed in
women, and 39,620 women will die from breast cancer in
the United States [2]. Thus, to facilitate disease preven-
tion, it is of great importance to identify potential risk
factors for breast cancer, especially the modifiable life-
style factors including diet [3]. Recently, an increasing
number of studies have been carried out to explore the
associations between red and/or processed meat intake
and the risk of breast cancer, but the results have been
inconsistent [4–9].
An early quantitative review done in 2010 demonstrated
that red meat and processed meat intake does not appear to
be independently associated with increased risk of breast
cancer [9]. Since then, five more epidemiologic studies
evaluating the association of red and processed meat intake
with breast cancer risk have yielded inconsistent results [4–
8]. Of these five studies, two prospective cohort studies in
2014 by Farvid et al. (including 88,803 and 44,231 women,
respectively) found a positive association between red meat
intake and breast cancer risk [4,5]. Another study using
data from the SU.VI.MAX study observed that processed
meat intake was prospectively associated with increased
breast cancer risk [6]. However, the other two studies re-
ported null associations [7,8]. Therefore, we conducted an
&Lixing Zhan
lxzhan@sibs.ac.cn
1
Key Laboratory of Food Safety Research, Institute for
Nutritional Sciences, Shanghai Institutes for Biological
Sciences, Chinese Academy of Sciences, University of
Chinese Academy of Sciences, 294 Taiyuan Road,
Shanghai 200031, China
2
Key Laboratory of Food Safety Risk Assessment, Ministry of
Health, Beijing 100021, China
123
Breast Cancer Res Treat (2015) 151:191–198
DOI 10.1007/s10549-015-3380-9
updated and comprehensive meta-analysis of prospective
studies to better characterize this issue.
Materials and methods
Search strategy
A computerized literature search was conducted in
PubMed (http://www.ncbi.nlm.nih.gov/pubmed) from its
inception through October 2014, by two independent re-
searchers. We searched the relevant studies with the fol-
lowing medical subject-heading terms and/or text words:
(1) breast cancer OR breast neoplasm; (2) meat OR red
meat OR processed meat OR preserved meat OR pork OR
beef OR veal OR mutton OR lamb OR ham OR sausage
OR bacon; (3) cohort OR prospective OR nested case–
control, following the meta-analysis of observation studies
in epidemiology guidelines [10]. Furthermore, we carried
out a broader search on diet or foods and breast cancer and
reviewed lists of the relevant articles to identify additional
studies. No language restriction was imposed.
Study selection
Studies were included in the meta-analysis if the studies
met the following criteria: (1) peer-reviewed publications
of prospective cohort studies or nested case–control stud-
ies; (2) the exposure studied was red meat or processed
meat, and the outcome of interest was incidence of or
mortality from breast cancer; and (3) relative risk (RR)
with corresponding 95 % CI was presented. If the articles
were duplicated or from the same study population, the
more recent or complete study was included. Case–control
studies, ecological assessments, correlation studies, ex-
perimental animal studies, and mechanistic studies were
excluded. We finally identified 14 prospective studies that
reported results for red meat or processed meat consump-
tion in relation to risk of breast cancer according to the
criteria listed above.
Data extraction
Two independent researchers extracted the following data
from each study: the first author’s last name, year of pub-
lication, country where the study was conducted, number
of cases, cohort size, years of follow-up, type of meat, RR
with corresponding 95 % CIs for the highest versus the
lowest level, and adjusted variables. Attempts were also
made to contact investigators if the data of interested were
not directly presented in the publications. When several
risk estimates were present, the estimates adjusted for the
greatest number of potential confounders were extracted.
The Newcastle–Ottawa scale was used to assess the study
quality [22].
Statistical analysis
A random-effects model was used to calculate the sum-
mary relative risks and 95 % CIs for the highest versus the
lowest level of red and processed meat intake. This model
was developed by DerSimonian and Laird, which accounts
for heterogeneity among studies [23]. For the dose-re-
sponse meta-analysis, we used generalized least squares
trend estimation analysis based on the methods proposed
by Greenland and Longnecker [24] and Orsini [25]. This
method requires the number of cases and non-cases (or
person-time) and the RR with its variance estimate for at
least three quantitative exposure categories. When studies
did not provide this information, we estimated the slopes
using variance-weighted least squares regression. When the
included studies used different units (such as servings and
times), we converted them into grams per day using 120 or
50 g as the average portion size for red meat or processed
meat, respectively [26].
Statistical heterogeneity among studies was evaluated
using the Cochran’s Q and I
2
statistics [27]. Heterogeneity
was considered present for P\0.05 or I
2
C50 %. Sources
of heterogeneity were explored in stratified analysis by
study location, menopausal status, and adjusted con-
founders. We also conducted sensitivity analysis to esti-
mate the influence of each individual study on the summary
results by repeating the random-effects meta-analysis after
omitting one study at a time. Publication bias was assessed
using funnel plots, and the further evaluated by Egger’s
linear regression and Begg’s rank correlation test [28,29].
A two-tailed Pvalue \0.05 was considered representative
of significant statistical publication bias. All statistical
analyses were performed using STATA, version 11.0
(STATA, College Station, TX).
Results
The flowchart of the identification of relevant studies is
shown in Fig. 1. A total of 172 articles were identified by
searching of the database, and 16 of these articles were
retrieved for full-text review. After excluding 2 publica-
tions that represented the same population, 14 cohort/nest
case–control studies were selected for use in our meta-
analysis. Characteristics of the included studies are shown
in Table 1. The 14 cohort studies [4,6,7,11–21] com-
prised a total of 1588,890 participants and 31,552 breast
cancer cases, and 3 studies were secondary analyses of
randomized controlled trial data [6,14,20]. Among the 14
studies evaluated, 6 were conducted in the United States, 6
192 Breast Cancer Res Treat (2015) 151:191–198
123
in Europe, 1 in North America and Western Europe, and 1
in Asia.
Red meat and breast cancer
Fourteen cohort studies that examined the association be-
tween red meat intake and the risk of breast cancer were
included in the meta-analysis. The summary RR of breast
cancer was 1.10 (95 % CI, 1.02–1.19) for subjects in the
highest category of red meat intake compared with those in
the lowest category. Statistically significant heterogeneity
was detected (P=0.001, I
2
=62.2 %). No publication
bias was observed by Begg’s test (P=0.44) or by Egger’s
test (P=0.08). Eleven studies [4,7,13–21] were eligible
to have required data for dose-response analysis, and
the estimated summary RR of breast cancer of an increase
in red meat intake of 120 g/day was 1.11 (95 % CI,
1.05, 1.16); no significant heterogeneity was observed
(P
heterogeneity
[0.1).
In stratified analysis by menopausal status, the summary
RR of breast cancer for subjects in the highest category of
red meat intake compared with those in the lowest category
was 1.08 (95 % CI, 0.95–1.22; n=5, P
heterogeneity
=0.22,
I
2
=30.9 %) for premenopausal women, and 1.20 (95 %
CI, 1.00–1.44; n=6, P
heterogeneity
=0.04, I
2
=56.6 %)
for postmenopausal women. Furthermore, in stratified
analysis by geographic region, the summary RR was
similar for studies conducted in the United States [RR, 1.10
(95 % CI, 0.97–1.25), n=6, P
heterogeneity
=0.024,
I
2
=61.3 %] and Europe [RR, 1.16 (95 % CI, 1.01–1.32),
P
heterogeneity
=0.038, I
2
=57.5 %] (Fig. 2).
When the overall homogeneity and effect size were
calculated by removing one study at a time, we confirmed
the stability of the positive association between red meat
intake and breast cancer risk (data not shown).
Processed meat and breast cancer
Twelve cohort studies [6,7,12–21] that examined the as-
sociation between processed meat intake and the risk of
breast cancer were included in the meta-analysis. The
summary RR of breast cancer was 1.08 (95 % CI,
1.01–1.15) for subjects in the highest category of processed
meat intake compared with those in the lowest category.
Statistically significant heterogeneity was detected
(P=0.006, I
2
=58.3 %), and publication bias was not
evidenced by Begg’s test (P=0. 30), but was observed by
Egger’s test (P\0.01). Seven studies [7,13,16–20] were
eligible to have required data for dose-response analysis,
and the estimated summary RR of breast cancer of an in-
crease in processed meat intake of 50 g/day was 1.09
(95 % CI, 1.03, 1.16); no significant heterogeneity was
observed (P
heterogeneity
[0.1) (Fig. 3).
In stratified analysis by menopausal status, the summary
RR of breast cancer for subjects in the highest category
of processed meat intake compared with those in the
lowest category was 1.03 (95 % CI, 0.89–1.18; n=3,
P
heterogeneity
=0.29, I
2
=20.4 %) for premenopausal
women, and 1.23 (95 % CI, 0.98–1.55; n =4, P
heterogeneity
=
0.06, I
2
=60.4 %) for postmenopausal women. Further-
more, in stratified analysis by geographic region, the
summary RR was 1.04 (95 % CI, 0.97–1.12) (n=4,
P
heterogeneity
=0.8, I
2
=0.0 %) for studies conducted in
the United States, and 1.16 (95 % CI, 1.05–1.28) (n=6,
P
heterogeneity
=0.21, I
2
=30.4 %) for studies conducted in
the Europe (Fig. 4).
Discussion
In this comprehensive updated meta-analysis, higher red and
processed meat intake was found to be associated with an
increased risk of breast cancer. The summary risk of breast
cancer for the highest versus the lowest categories increased
by 10 % for red meat, and 8 % for processed meat. The
results were consistent when using dose-response analysis.
A previous meta-analysis of red and processed meat
consumption and breast cancer was conducted by
Alexander et al. in 2009 [9]. That study found weak
positive summary associations across all meta-analysis
models, with the majority being non-statistically sig-
nificant. Moreover, only 11 studies were included in the
previous meta-analysis. However, since then, a number of
large-scale prospective epidemiologic studies have
evaluated the association between red and processed meat
intake and breast cancer risk. For example, one study with
Fig. 1 Flow diagram of study selection process
Breast Cancer Res Treat (2015) 151:191–198 193
123
Table 1 Characteristics of prospective studies of red meat and processed meat consumption and breast cancer risk
Author/
publication
year/country
Cohort Cases/cohort
size
Follow-up Exposure
details
RR (95 % CI)
(highest vs.
lowest)
Controlled variables
Byrne et al./
1996/United
States
NHANES
I/NHEFS cohort
53/6156 1982–1987 Beef 0.5 (0.3, 1.1) Age
Missmer et al./
2002/North
America and
Western
Europe
North America and
Western Europe
7379/351,041 1976–1997 Red meat 0.94 (0.87, 1.02) Age at menarche, interaction between
parity and age at first birth, oral
contraceptive use, history of benign
breast disease, family history of breast
cancer, smoking status, education,
BMI, height, alcohol, intake, total
energy intake, menopausal status,
interaction of BMI and menopausal
status, postmenopausal hormone use
Processed
meat
0.98 (0.96, 1.00)
van der Hel
et al./2004/
Dutch
Monitoring Project
on CVD Risk
Factors
229/551 1987–1997 Fresh red
meat
1.30 (0.83, 2.02) Age, menopausal status, town, energy
intake
Processed
meat
1.05 (0.67, 1.64)
Shannon et al./
2005/China
Shanghai breast
self-exam trial
378/1448 1989–2000 Red meat 1.24 (0.77, 1.99) Age, total energy intake, breast-feeding
Cured
meat
1.20 (0.82, 1.74)
Cho et al./2006/
United States
Nurses’ Health
Study II
1021/90,659 1991–2003 Red meat 1.27 (0.96, 1.67) Age, calendar year of interview,
smoking, height, parity, age at first
birth, BMI, age at menarche, family
history of breast cancer, history of
benign breast disease, oral
contraceptive use, alcohol intake,
energy intake
Processed
meat
1.08 (0.89, 1.31)
Taylor et al./
2007/UK
UK Women’s
Cohort Study
678/35,372 1995–2004 Red meat 1.41 (1.11, 1.81) Age, energy intake, menopausal status,
BMI, physical activity, smoking
status, HRT use, OCP use, parity, total
fruit and vegetable intake
Processed
meat
1.39 (1.09, 1.78)
Cross et al./
2007/United
states
NIH-AARP Diet
and Health study
5872/500,000 1995–2003 Red meat 1.02 (0.93, 1.12) Age, sex, education, marital status,,
family history of cancer, race, BMI,
smoking, physical activity, total
energy intake, alcohol intake, and fruit
and vegetable consumption
Processed
meat
1.03 (0.94, 1.12)
Egeberg et al./
2008/
Denmark
Diet, Cancer and
Health Cohort
Study
378/24,697 1993–2000 Red meat 1.65 (1.09, 2.50) Parity, age at first birth, education,
duration of HRT, intake of alcohol,
and BMI
Processed
meat
1.59 (1.02, 2.47)
Larsson et al./
2009/Sweden
Swedish
Mammography
Cohort
2952/61,433 1987–2007 Total red
meat
0.98 (0.80, 1.12) Education, BMI, height, parity, age at
first birth, age at menarche, age at
menopause, use of oral contraceptives,
use of postmenopausal hormones,
family history of breast cancer, intakes
of total energy and alcohol
194 Breast Cancer Res Treat (2015) 151:191–198
123
20 years of follow-up among 88,803 premenopausal
women from the Nurses’ Health Study II found that greater
intake of total red meat was associated with an increased
risk of breast cancer (highest vs. lowest quintiles, RR, 1.22;
95 % CI, 1.06–1.40; Ptrend =0.01) [4]. Another study
with 13-year follow-up by Farvid MS et al. (including
Table 1 continued
Author/
publication
year/country
Cohort Cases/cohort
size
Follow-up Exposure
details
RR (95 % CI)
(highest vs.
lowest)
Controlled variables
Processed
meat
1.08 (0.96, 1.22)
Ferrucci et al./
2009/United
States
Prostate, Lung,
Colorectal, and
Ovarian Cancer
Screening Trial
1205/52,158 1993–2001 Red meat 1.23 (1.00, 1.51) Age, race, education, study center,
randomization group, family history of
breast cancer, age at menarche, age at
menopause, age at first birth and
number of live births, history of
benign breast disease, number of
mammograms during past 3 years,
menopausal hormone therapy use,
BMI, alcohol intake, total fat intake,
and total energy intake
Processed
meat
1.12 (0.92, 1.36)
Pala et al./2009/
European
European
Prospective
Investigation into
Cancer and
Nutrition Cohort
7119/319,826 1992–2003 Red meat 1.06 (0.98, 1.14) Energy, height, weight, years of
schooling, smoking, and menopause
Processed
meat
1.10 (1.00, 1.20)
Genkinger
et al./2013/
United States
Black Women’s
Health Study
(BWHS)
1268/52,062 1995–2007 Red meat 1.02 (0.83, 1.24) Energy intake, age at menarche, BMI,
family history of breast cancer,
education, parity and age at first live
birth, oral contraceptive use,
menopausal hormone use, vigorous
physical activity, smoking status, and
alcohol intake
Processed
meat
0.99 (0.82, 1.20)
Takemi et al./
2014/United
States
Nurses’ Health
Study II
2830/88,803 1991–2011 Total red
meat
1.22 (1.06, 1.40) 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
Pouchieu et al./
2014/France
SU.VI.MAX Study 190/4684 1994–2007 Red meat 1.19 (0.79, 1.80) Age, intervention group, number of
dietary records, smoking status,
educational level, physical activity,
height, BMI, family history of breast
cancer, menopausal status at baseline,
use of HTM at baseline, number of
live births, without-alcohol energy
intake, alcohol intake, total lipid
intake. In addition, the red meat model
is adjusted for processed meat intake
and conversely
Processed
meat
1.45 (0.92, 2.27)
RR relative risk, CI confidence interval, BMI body mass index, OCP oral contraceptive pill, HRT hormone replacement therapy, HTM hormonal
treatment for menopause, NHANES National Health and Nutrition Examination Survey
Breast Cancer Res Treat (2015) 151:191–198 195
123
44,231 women) also observed that higher consumption of
total red meat in adolescence was significantly associated
with increased premenopausal breast cancer risk (highest
vs. lowest quintiles, RR, 1.43; 95 % CI, 1.05–1.94;
Ptrend =0.007) [5]. Using the data from the SU.VI.MAX
study, Pouchieu C et al. demonstrated that processed meat
intake was prospectively associated with increased breast
cancer risk (highest vs. lowest quartiles, RR, 1.45; 95 %
CI, 0.92–2.27, Ptrend =0.03) [6]. In the current updated
meta-analysis, after excluding the studies from the same
study population, we finally included 14 prospective stud-
ies and found statistically significant relationship between
red and processed meat consumption and breast cancer risk
(highest vs. lowest categories, summary RR, 1.10; 95 %
CI, 1.02–1.19 for red meat, and summary RR, 1.08; 95 %
CI, 1.01–1.15 for processed meat).
Several suggested biological mechanisms might explain
the positive association between red meat or processed meat
intake and breast cancer risk. The first mechanism concerns
the heme iron and non-heme iron. Iron, which has a pro-
oxidant activity, has been suggested as a risk factor for many
types of cancers [30]. However, epidemiological studies
have yielded mixed and contentious results regarding the
relationship between iron and breast cancer [20]. Moreover,
a cohort study included in our meta-analysis revealed that
adjusting for heme iron did not appreciably change the as-
sociation between red meat intake and breast cancer risk [4],
indicating that heme iron might not be a major causal fact
for the association between red meat intake and breast
cancer risk. Another important mechanism that may explain
the positive association relates to the presence of some
carcinogenic compounds like the heterocyclic amines
(HCAs) and polycyclic aromatic hydrocarbons (PAHs),
by-products that are produced in the process of high-tem-
perature cooking of red meat [31,32]. Several human
studies have demonstrated a positive association between
HCA and PAH intake and overall breast cancer risks [31,
33–38]. In addition, hormone residues of the exogenous
hormones used to treat beef cattle also are recognized as
possible sources of the positive association between red
meat intake and breast cancer risk [39,40]. Recently, a new
study published on PNAS has revealed that the animal sugar
molecule N-glycolylneuraminic acid (Neu5Gc), which is
highly enriched in red meat, would be absorbed and accu-
mulated in human tissues, and eventually lead to chronic
inflammation and tumor formation [41].
Our meta-analysis has several strengths. Firstly, the
assessment was based on prospective studies, which tend to
be less likely to have recall and selection bias than retro-
spective case–control studies. Moreover, our studies in-
cluded a large sample size (1588,890 participants and 31,552
breast cancer cases) which would have a much greater pos-
sibility of reaching detecting smaller associations and per-
forming subgroup analysis. However, there were also some
limitations in this meta-analysis. First, the inherent problems
of residual confounders in the included studies are of concern
in the meta-analysis of observational studies. Most of the
studies included in our meta-analysis controlled for a wide
range of confounders (such as age, BMI, and total energy
intake), and some of these studies even had controlled for
postmenopausal hormone treatment and Hormone replace-
ment therapy (of note, adjustment for all possible con-
founders might result in over-adjustment.). However, we still
cannot exclude the possibility that other inadequately mea-
sured factors such as environmental pollution [42,43] and
sleep quality [44], which might confound the association,
Fig. 2 Relative risks of breast
cancer comparing the highest
with the lowest category of red
meat consumption. Squares
indicate study-specific relative
risks (size of the square reflects
the statistical weight that each
study contribute to the summary
estimate); horizontal lines
indicate 95 % CI; diamond
indicates summary relative risk
estimate with corresponding
95 % CI
196 Breast Cancer Res Treat (2015) 151:191–198
123
should be included in the future studies. Second, our findings
are likely to be affected by the misclassification of meat. In
the studies included in our meta-analysis, the term ‘‘red
meat’’ referred to total red meat, corresponding to processed
red meat in some studies and to unprocessed red meat in other
studies. However, misclassification is generally non-differ-
ential in cohort studies, which would most likely attenuate
the association. Third, the intake quantity and consumption
levels in the highest and lowest categories varied across
studies, which might contribute the heterogeneity among
studies in the analysis of the highest versus the lowest intake
categories. To account for these differences, we also esti-
mated the relative risks of breast cancer for an increase intake
of red meat of 120 g/day and of processed meat of 50 g/day,
and similar results were observed. Finally, as with any meta-
analysis, publication bias could be of concern, because
studies with null results or small sample sizes tend not to be
published. Thus, the summary results may overestimate the
relative risk of breast cancer with red and/or processed meat
intake.
In conclusion, the overall results of the present study
suggest that high intake of red and/or processed meat is
associated with an increased risk of breast cancer. How-
ever, additional well-designed cohort or interventional
studies will be needed to confirm the association.
Acknowledgments The study was supported by grants from the
Ministry of Science and Technology of China (2011CB510104 and
2012CB945004), the National Natural Science Foundation of China
(31090362), the National Natural Science Foundation of China
(81071684), the Hundred Talents Program (2010OHTP11), Shanghai
PuJiang Talent program (11PJ1411200), and the Ministry of Science
and Technology of China (2012BAK01B00).
Conflict of interest The authors of this study have no conflict of
interest or any financial disclosures to make.
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