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HNUC#1776886, VOL 0, ISS 0
Carbohydrate Intake, Glycemic Index, and Glycemic Load and the
Risk of Breast Cancer among Iranian Women
Zeinab Alboghobeish, Azita Hekmatdoost, Saba Jalali, Maryam Ahmadi, and Bahram Rashidkhani
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Carbohydrate Intake, Glycemic Index, and Glycemic Load and the Risk of
Breast Cancer among Iranian Women
Zeinab Alboghobeish
a
, Azita Hekmatdoost
a
, Saba Jalali
a
, Maryam Ahmadi
b
, and Bahram Rashidkhani
c
a
Department of Clinical Nutrition and Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food
Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran;
b
Hamadan University of Medical Sciences
and Health Services, Hamedan, Iran;
c
Department of Community Nutrition, Faculty of Nutrition Sciences and Food Technology,
National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
ABSTRACT
Limited studies have conducted on the association between carbohydrate intake, glycemic
index (GI), glycemic load (GL), and BC risk among Middle Eastern women. Our objective was
to examine whether intake of carbohydrates, GI and GL would lead to more risk of BC
among Iranian women. In this case-control study, 136 women with histologically confirmed
BC and 272 control women were recruited. Dietary intake was assessed using a validated
168-item food frequency questionnaire (FFQ) from which GI and GL were estimated. We cal-
culated Odds ratios (OR) using logistic regression. The multivariate OR for the highest vs.
the lowest quartile was 2.49 (95% CI 1.28–4.82; Ptrend ¼0.005) for GI with a significant
trend. OR for GI and GL among postmenopausal women were 4.45 (95% CI 1.59–12.47; P
trend ¼0.002) and 4.15 (95% CI 0.87–19.67; Ptrend ¼0.03), respectively. OR for GI among
women with reduced vegetable intake was 13.55 (95% CI 3.90–46.99; Ptrend <0.001). Our
data suggest that high GI and GL play an important role in the risk of BC particularly among
postmenopausal woman.
ARTICLE HISTORY
Received 5 November 2019
Accepted 26 May 2020
Introduction
Breast cancer (BC) is the most common malignancy
diagnosed in women globally (1). The incidence of
this disease in the world is 1.2 million per year in
2018, of which 626,000 people have lost their lives
annually (1). BC is one of the most prevalent cancers
among women in Iran (2) and is rapidly increasing
(3). In 2012, the incidence rate and mortality of BC in
the country were estimated at 28.1 and 9.9 women
each year (per 100,000), respectively (4).
Various factors including genetic and environmen-
tal conditions (5) especially nutritional factors such as
alcohol consumption, high carbohydrate intake, diet
rich in simple sugars and low intake of fruits and veg-
etables are involved in the pathology of BC (6–9).
High intake of carbohydrate increases insulin levels
and subsequently stimulates cell proliferation and
inhibition of apoptosis in normal and breast cancer
cells by stimulating insulin receptors in the breast tis-
sue or indirectly by increasing IGF-I (10–12).
Physiological responses to the carbohydrate content of
the foods are measured by glycemic index (GI) and
glycemic load (GL)(13). GI shows the blood glucose
response 2 h, after consuming 50 grams of available
carbohydrates from a foodstuff compared to the
equivalent of a standard food such as glucose or white
bread(14). GL calculated by GI food items and carbo-
hydrates consumed in one serving(15). Thus, GI
shows the average quality of carbohydrate consump-
tion while GL diet represents the average quantity and
quality of dietary carbohydrates(16).
Studies that investigated the effects of GI and GL
as risk factors for BC have shown contradictory
results (7,13,17–22). A number of studies have
reported the direct relationship between GI and GL
with the risk of BC (13,19–22), while other studies
did not reach such effects (7,17,18).
To our knowledge, there is only one study has
already conducted on the relationship between GI and
GL with BC in Middle East and this study was carried
out with a small sample size without any sub-analysis
for the menopausal status (23). Thus, our goal in this
case-control study was to evaluate the relationship
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CONTACT Bahram Rashidkhani rashidkhani@yahoo.com Department of Community Nutrition, Faculty of Nutrition Sciences and Food Technology,
National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran 1981619573, Iran.
ß2020 Taylor & Francis Group, LLC
NUTRITION AND CANCER
https://doi.org/10.1080/01635581.2020.1776886
between carbohydrate, GI and GL with the risk of BC
according to menopausal status.
Patients and Methods
Study Design and Sample
In this hospital-based case-control study, cases were
136 women 30 years with a histologically confirmed
diagnosis of BC within the last 6 mo, who referred to
two general hospitals in Tehran (capital of Iran),
between September 2015 to February 2016. The con-
trols consisted of 272 women of similar age patients
who were admitted in other departments of the same
hospitals for a wide spectrum of nonmalignant dis-
eases that were irrelevant to alcohol abuse, smoking
and long-term diet modification. Conditions among
hospital controls included trauma and orthopedic
problems, disk disorders, acute surgical conditions,
eye, nose, ear and skin disorders. Controls and cases
were frequency matched by age (5-year groups). Less
than 8% of subjects came for the interview refused to
take part. Among participants, five controls and 2
cases withdrew from the analysis due to their energy
intakes was top and bottom three standard deviation
(SD) from the average population energy intakes.
Therefore, the final analysis of the data was performed
on 134 cases and 267 controls.
This study was carried out based on the guidelines
inserted in the Declaration of Helsinki and all proc-
esses related to the participants were approved by the
National Nutrition and Food Technology Research
Institute of Iran. Written informed consent was
obtained from each subject prior to enrollment.
Data Collection
All subjects were interviewed by professionally trained
dietitians. Physical activity level was determined using
a pre-tested questionnaire and data were indicated as
metabolic equivalent hours per day (MET-h/d) (24).
Additional information consisted of socio-demo-
graphic, lifestyle and clinical information was also col-
lected using a questionnaire in the same interview
procedure. The collected data consisted of socio-
demographic, lifestyle and clinical information. The
weight was measured using a digital scale with a pre-
cision of 0.1 kg (Seca, Hamburg, Germany) with min-
imal clothes without shoes. The height was measured
at a precision of 0.5 cm in standing position using a
wall mounted meter. Body mass index (BMI) was cal-
culated by dividing the weight (kg) by height
squared (m).
Dietary Assessment
Food intake was assessed in the year before diagnosis
(for cases) or interview date (for controls), using a
168 item validated and reliable food frequency ques-
tionnaire (FFQ) (25). This questionnaire contained the
Consumption frequency of each food item on a daily,
weekly, monthly and yearly. After converting intakes to
daily frequency, the household manual was used to
change the frequency of intakes to food consumption
in grams per day (26). Energy and nutrient content of
foods were calculated by the USDA dietary table.
Calculation of Glycemic Index and Glycemic Load
The values of the glycemic index of each carbohy-
drate-containing foodstuff as the percentage of gly-
cemic response compared to glucose (standard food)
comes from the International Glycemic Index Table
2008 (27) and data from the university of Sidney (28).
Since some Iranian food did not exist on the inter-
national table, for determining GI and GL, Iranian
food tables were used (29). GI value of each food item
for every subject calculated by multiplying the number
of servings of food per day in the carbohydrate avail-
able/serving of each food item and each foods GI.
Then, this value was divided by the total available
carbohydrate daily intake. Eventually, dietary GI for
each participant was achieved by summing the GI of
all food items together (30). Furthermore, GL was
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Table 1. Characteristics of breast cancer cases and controls,
Iranian breast cancer, Case control study, 2015–2016.
Cases (n¼134) Controls (n¼267)
Variables Mean SD Mean SD p value
Age 49.4 10.6 47.1 10.0 0.03
First pregnancy age 21.0 7.0 19.5 5.7 0.03
BMI 30.1 5.6 29.0 5.3 0.06
Physical activity (MET-h/d) 32.9 5.3 32.7 5.2 0.70
Total energy intake (kcal) 2562.5 612.8 2753.4 798.0 0.008
Available carbohydrate
intake (gr)
281.4 71.6 301.2 96.3 0.02
Total fiber intake (g) 36.5 14.3 39.8 18.5 0.04
number % number %
Smoking 0.86
Yes 4 3 9 3.4
No 130 97 258 96.6
Breast cancer family history 0.13
Yes 11 8.2 12 4.5
No 123 91.8 255 95.5
Menopausal status 0.03
Premenopausal 62 46.3 153 57.3
Postmenopausal 72 56.7 114 42.7
Education 0.31
Illiterate 13 10 24 9
Low education 55 42.3 134 50.4
High education 62 47.7 108 40.6
2 Z. ALBOGHOBEISH ET AL.
computed using the same method, however dividing
by 100 alternative of the total available carbohydrate
daily intake (15). Food items for which a GI had not
been determined were attributed to the GI of the
similar food (For example for GI of mandarin orange,
the GI of orange was replaced).
Statistical Analysis
Distributions of demographic, proposed risk factors,
clinical and dietary baseline characteristics were com-
pared between cases and controls using chi-square or
independent samples t test. Total available carbohy-
drate intake, GI and GL exposures were categorized as
quartiles based on the distribution among the con-
trols. Binary logistic regression method was applied to
estimate the odd ratios (ORs), 95% confidence inter-
vals (95% CI) and tests for trend for association of
available carbohydrate intake, GI, and GL (4th, 3rd
and 2nd quartiles vs. 1st quartile) with the risk of BC
while adjusting for other potential risk factors. Final
multivariate models included potential confounders
comprised of age (year), first pregnancy age, BMI,
physical activity (MET-h/day), current smoking (yes/
no), family history of BC (yes/no), menopausal status
(premenopausal/postmenopausal), education (illiterate,
Below diploma, diploma and university education),
total energy (kcal/day) and total fiber intake. Also to
assess whether the association of available carbohy-
drate, GI and GL with BC varied with menopausal
status or the amount of vegetable intake, analyses
were performed separately according to menopausal
status and vegetable intake (<307 and 307 gr/day).
All statistical analyses were performed by using SPSS
software version 25.0 (SPSS Inc., Chicago, IL, USA).
All P-values were according to 2-sided and the level
of significance were set at P-value <0.05.
Results
The distribution of known risk factors for breast can-
cer and socio-demographic characteristics of the 134
cases and 267 controls are reported in Table 1. There
were no differences between cases and controls in
BMI, physical activity level, smoking, BC family his-
tory and educational level. Compared with controls,
cases were older and reported a higher first pregnancy
age. Furthermore, cases were more likely to be post-
menopausal than controls (56.7% vs. 42.7%, P¼0.03).
Moreover, the mean (SD) of total energy, fiber and
available carbohydrate intakes were significantly lower
among cases (compared to controls).
Table 2 indicates the ORs and the corresponding
95% CIs for BC based on quartiles of dietary GI, GL,
and available carbohydrate intake among overall
women. No significant associations emerged for avail-
able carbohydrate intake and dietary GL with risk of
BC in the age-adjusted model (model 1), the model
adjusted additionally for known BC risk factors
(model 2), or the model adjusted additionally for total
fiber intake, Smoking, education level and menopausal
status (model 3). However, there was a significant
positive association between GI and risk of BC. The
multivariate adjusted OR comparing the highest with
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Table 2. Distribution of 134 breast cancer cases and 267 controls, according to available carbohydrates, glycemic index and gly-
cemic load in overall (Odds ratios and 95% confidence intervals).
Model 1 Model 2 Model 3
Quartiles of Carbohydrates, GI and GL Case/Control OR 95% CI OR 95% CI OR 95% CI
Available carbohydrates (g/day)
<230.1 36/64 1.00 ref 1.00 ref 1.00 ref
230.1–281.3 38/63 1.09 0.61–1.94 1.22 0.65–2.31 1.24 0.65–2.36
281.3–337.6 34/65 0.93 0.51–1.67 1.22 0.58–2.57 1.17 0.55–2.50
>337.6 26/75 0.62 0.34–1.14 1.09 0.41–2.90 1.05 0.38–2.87
P trend 0.11 0.77 0.85
Glycemic index
<46.6 33/68 1.00 ref 1.00 ref 1.00 ref
46.6–48.5 25/75 0.67 0.36–1.26 0.83 0.42–1.62 0.78 0.39–1.56
48.5–50.5 30/70 0.90 0.49–1.65 0.98 0.51–1.90 0.99 0.50–1.94
>50.5 46/54 1.78 1.00–3.17 2.35 1.24–4.43 2.49 1.28–4.82
P trend 0.02 0.006 0.005
Glycemic load
<111.2 30/71 1.00 ref 1.00 ref 1.00 ref
111.2–135.6 42/57 1.78 0.99–3.22 2.11 1.10–4.04 2.28 1.18–4.42
135.6–169.1 40/60 1.65 0.91–2.98 2.16 1.06–4.42 2.16 1.04–4.49
>169.1 22/79 0.67 0.35–1.27 1.25 0.49–3.23 1.37 0.51–3.63
P trend 0.24 0.32 0.28
Model 1: adjusted for age only.
Model 2: adjusted for age, age at first pregnancy, BMI, family history of breast cancer, Physical activity, total energy intake.
Model 3: adjusted for age, age at first pregnancy, BMI, family history of breast cancer, Physical activity, total energy intake, total fiber intake, Smoking,
education level and menopausal status.
NUTRITION AND CANCER 3
the lowest quartile was 2.49 (95% CI ¼1.28, 4.82; P
trend ¼0.005).
When analyses were stratified by menopausal status
(Table 3), a positive significant association was
detected between GI and risk of BC just among post-
menopausal women (Ptrend ¼0.002). Furthermore,
among postmenopausal women GL was associated
with increased risk of BC (Ptrend ¼0.03).
Since vegetables may neutralize the glycemic
response of food, the associations between available
carbohydrate intake, GI, GL and BC risk were further
assessed according to the vegetable consumption
(<307 and 307 g/d). Among women with vegetable
intake below the median (307 g/d) elevated dietary GI
was associated with an increased risk of BC (OR ¼
13.55, 95% CI: 3.90–46.99 for the highest category).
Although no such result was found for people vege-
table intake above this level (Table 4).
Discussion
In this hospital-based case control study, we found a
positive significant association of high overall GI, a
representative of quality of carbohydrate intake with
BC risk; however, dietary GL and total available
carbohydrate had no relation to risk. Dramatically,
this association was more strong in two groups of
women—in postmenopausal status and those with low
intake of vegetables. Although overall GL was not
associated with risk, we observed significant excess of
BC risk with elevated GL only among postmeno-
pausal women.
It has been previously shown that there is a direct
relationship between blood glucose level and IGF1
(28,31) high glycemic diet increases circulating glu-
cose concentrations and subsequently raises insulin
secretion (32). High concentration of insulin may
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Table 3. Distribution of 134 breast cancer cases and 267 controls, according to available carbohydrates, glycemic index and gly-
cemic load by menopausal Status (Odds ratios and 95% confidence intervals).
Model 1 Model 2 Model 3
Menopausal Status Quartiles of Carbohydrates,GI and GL Case/Control OR 95% CI OR 95% CI OR 95% CI
Premenopausal Available carbohydrates (g/day)
<230.1 19/33 1.00 ref 1.00 ref 1.00 ref
230.1–281.3 17/40 0.73 0.32–1.63 0.77 0.32–1.86 0.73 0.30–1.77
281.3–337.6 13/36 0.62 0.26–1.46 0.74 0.25–2.17 0.70 0.23–2.06
>337.6 13/44 0.51 0.22–1.18 0.89 0.21–3.70 0.72 0.17–3.10
P trend 0.10 0.75 0.58
Glycemic index
<46.6 16/38 1.00 ref 1.00 ref 1.00 ref
46.6–48.5 12/39 0.73 0.30–1.75 0.73 0.27–1.93 0.76 0.28–2.04
48.5–50.5 16/44 0.86 0.37–1.96 0.87 0.34–2.23 0.82 0.31–2.13
>50.5 18/32 1.33 0.58–3.03 1.71 0.67–4.37 1.80 0.68–4.70
P trend 0.46 0.23 0.23
Glycemic load
<111.2 15/36 1.00 ref 1.00 ref 1.00 ref
111.2–135.6 18/35 1.23 0.53–2.83 1.37 0.55–3.40 1.35 0.54–3.35
135.6–169.1 20/38 1.26 0.56–2.84 1.43 0.52–3.91 1.35 0.48–3.73
>169.1 9/44 0.49 0.19–1.25 0.87 0.21–3.50 0.89 0.22–3.60
P trend 0.19 0.88 0.92
Postmenopausal Available carbohydrates (g/day)
<230.1 17/31 1.00 ref 1.00 ref 1.00 ref
230.1–281.3 21/23 1.75 0.75–4.07 2.62 0.98–7.04 3.03 1.09–8.38
281.3–337.6 21/29 1.38 0.60–3.15 3.00 0.97–9.27 3.25 1.00–10.52
>337.6 13/31 0.79 0.32–1.92 2.46 0.56–10.73 2.89 0.62–13.46
P trend 0.56 0.15 0.11
Glycemic index
<46.6 17/30 1.00 ref 1.00 ref 1.00 ref
46.6–48.5 13/36 0.62 0.25–1.49 0.83 0.30–2.27 0.69 0.24–2.00
48.5–50.5 14/26 1.02 0.41–2.49 1.19 0.42–3.36 1.34 0.45–3.95
>50.5 28/22 2.40 1.05–5.50 3.85 1.48–10.00 4.45 1.59–12.47
P trend 0.01 0.003 0.002
Glycemic load
<111.2 15/35 1.00 ref 1.00 ref 1.00 ref
111.2–135.6 24/22 2.70 1.15–6.29 4.12 1.48–11.49 5.19 1.75–15.40
135.6–169.1 20/22 2.26 0.95–5.39 5.05 1.62–15.76 5.68 1.70–18.92
>169.1 13/35 0.92 0.37–2.23 2.82 0.69–11.49 4.15 0.87–19.67
P trend 0.77 0.08 0.03
Model 1: adjusted for age only.
Model 2: adjusted for age, age at first pregnancy, BMI, family history of breast cancer, Physical activity, total energy intake.
Model 3: adjusted for age, age at first pregnancy, BMI, family history of breast cancer, Physical activity, total energy intake, total fiber intake, Smoking
and education level.
4 Z. ALBOGHOBEISH ET AL.
increase the risk of BC whether directly, by stimula-
tion of insulin receptors in breast tissue, or indirectly,
through the mitogenic signals of insulin-like growth
factor I (IGF-I) (33). On the other hand, insulin and
IGF1 receptors are involved in pathways that stimu-
late proliferation and inhibit apoptosis (10,11).
Another mechanism in the pathogenesis of BC may
also be the interaction of insulin/IGF system with the
expression of estrogen receptor through GPER (G-
protein estrogen receptor) in normal breast cell as
well as in breast tumor cells (34,35). Probably
because the carbohydrate intake was higher in the
control group and GL incorporates of both quality
and quantity of carbohydrate consumed(36), overall
GL and available carbohydrates intake had no influ-
ence on BC risk. In addition, in postmenopausal
women, the risk of BC increases with promotion of
insulin resistance due to estrogen depletion and subse-
quent impairment of glucose transport into the cells
(37,38). Likely, due to the mechanism mentioned,
results suggested an increased risk related to both
dietary GI and GL among premenopausal women, but
not premenopausal women.
In the present study, the highest dietary GI vs. the
lowest one was associated with a 2.5-fold increase in
BC risk. Previous studies of overall GI, GL and total
carbohydrate exhibited different outcome. For
instance, some previous studies reported overall GI
and GL are not related to BC risk (7,39–42). In keep-
ing with our results, a recent meta-analysis of ten pro-
spective cohort studies indicated that high GI diet was
associated with a significantly increased risk of BC
(RR ¼1.08, 95% CI: 1.02–1.14), albeit dietary GL had
no interaction with risk of BC (43). Similarly, another
meta-analysis of 37 prospective observational studies
reported statistically significant increased risks related
to the top vs. bottom quintile of overall GI (RR ¼
1.08, 95% CI: 1.02–1.16) (22). Additional studies
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Table 4. Distribution of 134 breast cancer cases and 267 controls, according to available carbohydrates, glycemic index and gly-
cemic load by vegetable intake (Odds ratios and 95% confidence intervals).
Model 1 Model 2 Model 3
Vegetable intake (g/d) Quartiles of Carbohydrates, GI and GL Case/Control OR 95% CI OR 95% CI OR 95% CI
<307 Available carbohydrates (g/day)
<230.1 29/44 1.00 ref 1.00 ref 1.00 ref
230.1–281.3 22/32 1.02 0.49–2.12 1.13 0.50–2.57 1.13 0.49–2.59
281.3–337.6 15/32 0.68 0.31–1.48 0.82 0.29–2.29 0.83 0.29–2.38
>337.6 12/14 1.30 0.52–3.25 1.56 0.37–6.51 2.20 0.49–9.89
P trend 0.94 0.82 0.65
Glycemic index
<46.6 6/26 1.00 ref 1.00 ref 1.00 ref
46.6–48.5 14/33 1.83 0.61–5.50 2.65 0.75–9.31 2.79 0.77–10.11
48.5–50.5 18/37 2.26 0.78–6.56 2.55 0.76–8.60 2.87 0.83–9.87
>50.5 40/26 6.83 2.44–19.10 10.53 3.23–34.36 13.55 3.90–46.99
P trend <0.001 <0.001 <0.001
Glycemic load
<111.2 21/44 1.00 ref 1.00 ref 1.00 ref
111.2–135.6 24/29 1.82 0.85–3.90 2.33 0.98–5.48 2.48 1.02–5.99
135.6–169.1 21/29 1.61 0.73–3.51 2.06 0.78–5.44 2.17 0.80–5.89
>169.1 12/20 1.25 0.51–3.07 2.09 0.55–7.94 2.97 0.69–12.79
P trend 0.49 0.17 0.10
307Available carbohydrates (g/day)
<230.1 7/20 1.00 ref 1.00 ref 1.00 ref
230.1–281.3 16/31 1.59 0.55–4.64 1.79 0.56–5.70 1.77 0.54–5.79
281.3–337.6 19/33 1.76 0.62–4.98 2.55 0.73–8.93 2.39 0.65–8.71
>337.6 14/61 0.70 0.24–2.02 1.37 0.30–6.17 0.98 0.20–4.80
P trend 0.23 0.65 0.95
Glycemic index
<46.6 27/42 1.00 ref 1.00 ref 1.00 ref
46.6–48.5 11/42 0.40 0.17–0.91 0.48 0.20–1.15 0.43 0.17–1.08
48.5–50.5 12/33 0.56 0.24–1.28 0.64 0.26–1.55 0.62 0.24–1.58
>50.5 6/28 0.33 0.12–0.92 0.48 0.16–1.43 0.44 0.13–1.41
P trend 0.03 0.18 0.16
Glycemic load
<111.2 9/27 1.00 ref 1.00 ref 1.00 ref
111.2–135.6 18/28 1.96 0.74–5.13 1.94 0.68–5.53 2.23 0.76–6.53
135.6–169.1 19/31 1.92 0.74–4.98 2.10 0.68–6.46 2.17 0.66–7.05
>169.1 10/59 0.53 0.19–1.46 0.68 0.16–2.97 0.65 0.14–2.99
P trend 0.10 0.83 0.76
Model 1: adjusted for age only.
Model 2: adjusted for age, age at first pregnancy, BMI, family history of breast cancer, Physical activity, total energy intake.
Model 3: adjusted for age, age at first pregnancy, BMI, family history of breast cancer, Physical activity, total energy intake, total fiber intake, Smoking,
education level and menopausal status.
NUTRITION AND CANCER 5
present evidence that foods with high GI and GL, or
GL alone were positively associated with BC risk (20,
21,23,44–46).
In attempting to explain these differences, it is
important to highlight that these indices display dif-
ferent aspects of carbohydrate consumed. Dietary GI
gives information on overall quality of carbohydrates
in the diet, whereas dietary GL, by considering the
amount of carbohydrate intake, includes both the
quality and quantity of dietary carbohydrate intake
(36). Therefore, women with BC may have consumed
a wide range of foods with high GI but not consumed
a large amount of this foods compared to women
who did not have BC) so their diet was poor in carbo-
hydrate quality (.
Moreover, the results of this study indicate that the
associations between BC risk and GI may be stronger
among subjects with a reduced vegetable consumption
(<307 g/d) than in those with more intakes of vegeta-
bles (>307 g/d). A European cohort study (EPIC) sug-
gested a significant increased risk of BC with high
dietary GL in women with low fiber intake. Also, high
dietary GI was related to BC risk among postmeno-
pausal women reporting low dietary fiber consump-
tion (41). The proposed mechanism for this result is
that vegetable ingredients including fibers slow down
gastric emptying, delay amylolytic process in the small
bowel and modify carbohydrate absorption that ultim-
ately causes alleviating the glycemic effect (47,48).
When women stratified by menopausal status, high
GI and GL foods were related to a greater BC risk in
postmenopausal women, but not in premenopausal
women. Previous studies have achieved contradictory
results. Our results are consistent with a Korean case-
control study that reported BC risk was directly asso-
ciated with both GI and GL among postmenopausal
women (20). In another population-based case–con-
trol Study observed significantly direct association
between dietary GL alone and BC risk among postme-
nopausal Mexican women (45). In the prospective
Canadian National Breast Screening Study (NBSS),
Navarro Silvera et al. also indicated that high dietary
GI alone was associated with increased BC risk in
postmenopausal women (39). Likewise, two meta-ana-
lysis performed by Mulholland et al. and Schlesinger
et al. emerged that only the GL or GL had a positive
relationship with BC risk in these women (13,49). In
contrast, several prospective cohort studies have
shown these indices were unrelated with BC risk
among postmenopausal women (17,40,44,50). Our
findings are in agreement with previous published
data that reported absence of relationship between GI/
GL and BC risk in premenopausal women (7,13,39,
44,45,49). Conversely, other studies demonstrated a
higher risk of BC related to dietary GI or GL among
these women (20,40,46)
With regard to carbohydrate, our findings are con-
sistent with EPIC study that suggested no association
between carbohydrate and risk of BC (19,21,39,41);
however, some studies demonstrated that high dietary
carbohydrate was related to increased BC risk in over-
all or premenopausal women (7,51). These conflicting
results may be because of the disparities of dietary
carbohydrate intake and nutritional habits among the
study populations.
The strengths of present study include usage of a
validated and reliable food-frequency questionnaire.
The questionnaire, containing 168 items, has been
developed particularly to estimate the food items con-
sumed in Iran (25). To measure GL and GI, in add-
ition to applying international tables of GI and GL
values of 2008 (27), for number of foods (such as
Iranian bread) that are not documented in these
tables, the GI of Iranian food table was used. In add-
ition, high participation rate of patients is another
strength in our investigation. Also, this is the first
study in Iranian population that examined the rela-
tionship between GI/GL and BC risk with stratifica-
tion by menopausal status and amount of vegetable
intake. Despite these strengths, several limitations also
are inherent in our study. Recall bias is a limitation in
each dietary research and case-control study in the
data collection because of using questionnaires to
quantify dietary intake. Nonetheless, the patients who
were Over-reporting or under-reporting their energy
consumption ignored in data analysis. Furthermore, it
is probably difficult to avoid selection bias; although,
the high rate of participation (>90%), utility of new
incident of BC women and hospital controls, and
employing professional dietitian for administering
FFQs attenuated these potential problems. Likely con-
founding factors would be existed, however adjust-
ment for many recognized risk factors for BC
decreases this possibility. It should be pointed out that
the sample size in this study is lower than
prior studies.
In conclusion, present study has found a positive
association between diets high in GI/GL and the pro-
gress of BC, particularly in postmenopausal women.
We also observed strong relation between high GI
and BC in women with low vegetable intake, which
suggests that additional investigations are needed to
achieve clear results in this context, especially accord-
ing to special BC subsets.
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6 Z. ALBOGHOBEISH ET AL.
Disclosure Statement
The authors disclosed that they have no conflicts of interest.
Author Contributions
ZA and BR developed the proposal, obtained ethical appro-
vals, applied for funding, supervised data collection and pre-
pared the first draft. ZA, AH, MA, and SJ conceived the
idea, provided analysis of the study. ZA and BR were
involved in study analysis. All authors read and approved
the final manuscript.
Funding
This study was funded by the National Nutrition and Food
Technology Research Institute, Shahid Beheshti University
of Medical Sciences, Tehran, Iran.
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893
894
895
896
897
898
899
900
901
902
903
904
905
906
907
908
909
910
911
912
913
914
915
916
917
918
919
920
921
922
923
924
925
926
927
928
929
930
931
932
933
934
935
936
937
938
939
940
941
942
943
944
945
946
947
948
949
950
951
952
NUTRITION AND CANCER 9
