RESEARCH

Original Research: Brief

Chocolate Candy and Incident Invasive Cancer

Risk in the Women’s Health Initiative: An
Observational Prospective Analysis
James A. Greenberg, PhD; Marian L. Neuhouser, PhD, RD; Lesley F. Tinker, PhD, RD; Dorothy S. Lane, MD, PhD;
Electra D. Paskett, MSPH, PHD; Linda V. Van Horn, PhD; Sylvia Wassertheil-Smoller, PhD; James M. Shikany, DrPH; Lihong Qi, PhD;
Shawnita Sealy-Jefferson, PhD, MPH; JoAnn E. Manson, MD, DrPH

ARTICLE INFORMATION ABSTRACT

Article history: Background Laboratory and animal studies suggest an inverse association between
Submitted 10 October 2019 chocolate consumption and the risk of cancer. Epidemiological studies have yielded
Accepted 9 June 2020 inconsistent evidence.
Objective To assess the association of chocolate candy consumption with incident,
Keywords: invasive total, breast, colorectal, and lung cancers in a large cohort of postmenopausal
Women’s Health Initiative American women.
Chocolate consumption
Invasive cancer
Design Prospective cohort study with a mean 14.8-year follow-up. Chocolate candy
Invasive colorectal cancer intake was assessed by food frequency questionnaire. Invasive cancer events were
Obesity assessed by physician adjudication.
Participants/setting The Women’s Health Initiative Study enrolled 161,808 post-
Supplementary materials:
Tables 3, 4, and 5 and the Appendix are available at
menopausal women at 40 clinical centers nationwide between 1993 and 1998. Of these
www.jandonline.org. women, 114,281 with plausible food frequency or biometric data and no missing data on
chocolate candy exposure were selected for analysis.
2212-2672/Copyright ª 2021 by the Academy of
Main outcome measures Cancer risk in quartiles of chocolate candy consumption with
Nutrition and Dietetics. the first quartile as referent.
https://doi.org/10.1016/j.jand.2020.06.014 Statistical analyses Multivariable Cox regression was used to calculate hazard ratios
and 95% confidence intervals.
Results There were 16,164 documented incident invasive cancers, representing an inci-
dence rate of 17.0 per 100 participants and 12.3 per 1000 person years during follow-up
among participants without any preexisting cancers or missing outcome data. There were
no statistically significant associations for total invasive cancer (P-linear ¼ .47, P-
curvature ¼ .14), or invasive breast cancer (P-linear ¼ .77, P-curvature ¼ .26). For colo-
rectal cancer P-linear was .02, P-curvature was .03, and compared with women eating a 1
oz (28.4 g) chocolate candy serving <1 time per month, the hazard ratio for 1.5 times/
wk was 1.18 (95% confidence interval: 1.04-1.35). This result may be attributable to the
excess adiposity associated with frequent chocolate candy consumption.
Conclusions In the Women’s Health Initiative, there was no significant association
between chocolate candy consumption and invasive total or breast cancer. There was a
modest 18% higher risk of invasive colorectal cancer for women who ate chocolate
candy at least 1.5 times/wk. These results require confirmation.
J Acad Nutr Diet. 2021;121(2):314-326.

A
LARGE AND GROWING BODY OF EVIDENCE SUG-
gests that flavonoids in chocolate and cocoa have
the potential to decrease the risk of cancer in
humans.1-9 Chocolate, particularly dark chocolate, is
a major source of flavonoids, a subgroup of dietary phyto-
chemicals.1 Cocoa flavonoids are thought to reduce the risk of
cancer via a number of biological mechanisms that include
enhancing immune response,2 decreasing indicators of
oxidative stress,3 modulating inflammatory responses,4,5
apoptosis,6 cellular proliferation, and reducing angiogenesis
and metastasis.8
Most of the evidence for an anticancer potential in chocolate
is from laboratory and animal studies.8 To date, there have
been no published long-term randomized trials of the effects
of chocolate on cancer risk in humans. Some small-scale short-
term human trials have yielded evidence indicating that
chocolate or flavonoid intake has beneficial effects on factors
that could attenuate oncogenesis such as antioxidant capacity
and inflammatory markers.9 One ecologic study found an in-
verse association between cocoa intake and cancer among the
Kuna tribe living in the Panamanian San Blas islands, a pop-
ulation documented to have a high cocoa intake.10

314 JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS ª 2021 by the Academy of Nutrition and Dietetics.

Results from observational epidemiological studies are
mixed, although most have found no association between
chocolate intake and cancer risk.11-15
The objective was to add empirical evidence from a pro-
spective study on the association between chocolate intake
and the risk of cancer in postmenopausal American women. A
priori null hypotheses were that in the prospective Women’s
Health Initiative (WHI) cohort there would be no significant
associations between chocolate candy (chocolate) intake and
the risk of total cancer and the 3 most common cancer
types—breast, colorectal, and lung cancer. An additional hy-
pothesis was that body mass index (BMI) is a mediator var-
iable in the association between chocolate consumption and
risk of the 2 cancers for which excess adiposity is an estab-
lished risk factor—breast and colorectal cancers.16
MATERIALS AND METHODS
Participants
The design and conduct of the WHI have been described
previously.17 Briefly, 161,808 postmenopausal women 50 to
79 years of age were enrolled into the WHI observational
study (OS) or 1 or more overlapping clinical trials (CTs) be-
tween 1993 and 1998. The OS is a prospective follow-up
study. Data on OS and CT participant characteristics and
morbidity and mortality are collected on a continuing basis.
Follow-up for our analysis ended on February 28, 2017.
Of the original 161,808 women, 93,676 OS and 68,132 CT
subjects, all OS and CT participants in a control arm (CT
controls) were selected. Next, the following women were
excluded: those (1) with implausible self-reported energy
intake by food frequency questionnaire (FFQ), defined as
<600 kcal/d or >5000 kcal/d; (2) with implausible anthro-
pometric measures, including BMI, defined as <15 or >50,
and height, defined as <122 cm (4 ft); (3) with preexisting
cancer or missing values on preexisting cancer at baseline;
and (4) with missing values for any outcome or covariate
variables This left 95,046 women who provided the data used
in the analysis for total cancer (see Fig 1); and 95,342 for
breast cancer, 104,845 for colorectal cancer, and 105,374 for
lung cancer.
Data were missing for <1.5% for all predictor, outcome, and
confounder variables, except for the following 4 covariates:
use of female hormones (the missing percentage was 2.4%),
recreational physical activity (2.9%), previous colonoscopy or
sigmoidoscopy (3.3%), and preexisting emphysema (4.7%).
Chocolate Intake
The exposure variable, chocolate consumption, was assessed
by the baseline self-administered WHI FFQ.18 A single line
item on chocolate asked how often over the past 3 months
the participant ate a portion of “chocolate candy and candy
bars” and to specify whether the portion was small (0.5 oz or
14.2 g), medium (1 oz or 28.4 g), or large (0.75 oz or 42.6 g).
There were 9 frequency options—never or less than monthly,
1 per month, 2 to 3 per month, 1 per week, 2 per week, 3 to 4
per week, 5 to 6 per week, 1 per day, and 2 or more per day.
Each participant’s responses were converted by WHI re-
searchers into the number of medium (1 oz) servings per day.
For this study, 4 levels of intake frequency of a 1 oz serving of
chocolate were derived from the WHI data: <1 time/mo, 1
time/mo to <0.5 times/wk, 0.5 times/wk to <1.5 times/wk,
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RESEARCH SNAPSHOT
Research Question: Is long-term consumption of chocolate
candy associated with increased risk of invasive cancers
among postmenopausal American women?
Key Findings: In this prospective study within the Women’s
Health Initiative cohort, there was no significant association
between chocolate candy consumption and invasive total or
invasive breast cancer. There was a significant modest 18%
higher risk of invasive colorectal cancer for women who ate
at least 1.5 oz of chocolate candy per week.
and 1.5 times/wk. Cut points were selected that resulted in
levels corresponding as closely as possible to quartiles, given
that the lowest level (<1 time/mo) contained more than 30%
of cases. A continuous version of chocolate intake was also
created—the number of 1 oz servings consumed per day.
Outcome Variables
The outcome event was the first occurrence of the invasive
cancer being analyzed. Cancers graded as in situ and cancer
deaths were excluded. For total cancer, all forms of cancer
except nonmelanoma skin cancer were included. All reported
events were confirmed and adjudicated based on reviews of
medical records and pathology reports by trained WHI phy-
sicians.19 Participants were followed from the baseline survey
(1993-1998) to the first occurrence of the cancer being
analyzed, loss to follow-up, or the end of follow-up on
February 28, 2017, whichever occurred first. Participants were
censored if and when they were lost to follow-up or died
from a cause other than the cancer being analyzed. Partici-
pants were also censored if and when they were diagnosed
with a cancer different from the cancer being analyzed prior
to the first occurrence of the cancer being analyzed. None of
the outcome events changed during the course of the study
or during post hoc analyses.
Covariates
Two regression models were built for each type of cancer. In
the basic model the covariates were age in years; race or
ethnicity (White, Black, Hispanic or other); and WHI study
arm (OS or CT controls). All full models included the
following established risk-factor variables: smoking status
(never, past, or current smoker); total recreational energy
expended in metabolic equivalent of task hours per week
including walking and mild, moderate, and strenuous phys-
ical activity; nonchocolate daily energy intake20; the Revised
Alternative Healthy Eating Index21; alcohol intake with 6
levels; and education (<high school, some high school to
<college, some college to <postgraduate study, or
postgraduate study or degree). Full models were also
adjusted for additional covariates for the following cancers:
(1) for total cancer: close relatives with a history of any type
of cancer (none, 1 male or female relative, or both a male and
female relative); (2) for breast cancer: total months spent
breastfeeding; number of live births; female hormone usage
(never, previous or current); previous mammograms (yes or
no); close relatives with age <45 years and a history of breast
cancer (0-5); age at menopause; and a Gail model-2
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Figure 1. Participant flowchart for total cancer, showing the number of available participants, the numbers meeting different
inclusion criteria, and the number included in the analytic sample. BMI ¼ body mass index; FFQ ¼ food frequency questionnaire;
WHI ¼ Women’s Health Initiative.

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Figure 2. Chocolate candy intake and the risk of total cancer in the Women’s Health Initiative. CI ¼ confidence interval; CL ¼
confidence limit.
variable,22 which replaced age and race or ethnicity; (3) for
colorectal cancer: number of close female or male relatives
with age < 45 years and preexisting colorectal cancer; prior
colonoscopy (yes or no); preexisting diabetes (yes or no); and
preexisting ulcerative colitis or Cohn’s disease (yes or no);
and (4) for lung cancer: preexisting emphysema (yes or no).
BMI was not included as a covariate in the main analyses
due to its potential role as a mediator variable. BMI was
tested for interaction effects. In a sensitivity analysis, the ef-
fects of including BMI as a covariate were assessed.
Statistical Power Calculations
Equation 1 in Hsieh and Lavori23 was used to estimate the
number of events needed to be able to detect a hazard ratio
(HR) decrease of 0.20 or an increase of 0.25 at the 2-sided 5%
significance level with a statistical power of 80%. It was
assumed that the predictor was divided into quartiles and
that the survival analyses were performed with Cox regres-
sion. The number of needed events was estimated as 1686.
Statistical Methods
Multivariable adjusted Cox regression HRs were estimated for
each outcome cancer event in different levels of chocolate
intake frequency and for a 1 oz/d (28.4 g/d) increment. The
proportional hazards assumption was tested by means of
Schoenfeld residuals. The effects of potential non-
proportionality on HR estimates were assessed by means of
time-dependent Cox regression analysis.24,25 This latter
analysis showed that the potential nonproportionality caused
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essentially no changes in HR estimates or 95% confidence
intervals (CIs).
Restricted-cubic-splines26 versions of continuous cova-
riates and ordinal and categorical covariates with 5 levels
were used if they caused a significant increase in the model’s
likelihood ratio. Figures 2 through 5 and P-curvature27 were
derived from Cox regression analyses in which the exposure
variable was a restricted cubic splines version of the
exposure.
Significance of the linear trend across quartiles of chocolate
intake (P-linear) used the median value in each quartile as a
continuous variable. Differences between the fit of restricted
cubic splines curves in Figures 2 through 5 and linear curves
were assessed by means of the likelihood ratio test.
Based on a priori hypotheses, BMI was tested for interac-
tion effects by inserting a cross-product of the predictor and
BMI into the full model.
Two-sided P < .05 was considered significant, except that
2-sided P < 0.1 was the criterion for tests of interaction. SAS
version 9.4 (SAS Institute Inc, Cary, NC, 2019) was used for all
analyses.
The WHI study is registered at Clinictrials.gov
(#NCT00000611). The manuscript was prepared using the
STROBE guidelines for observational studies.28
Ethical Statement
The WHI study protocol (available at www.whi.org) was
approved by institutional review boards at each participating
institution, and all participants provided written informed
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Figure 3. Chocolate candy intake and the risk of invasive breast cancer in the Women’s Health Initiative. CI ¼ confidence interval;
CL ¼ confidence limit.

Figure 4. Chocolate candy intake and the risk of invasive colorectal cancer in the Women’s Health Initiative. CI ¼ confidence in-
terval; CL ¼ confidence limit.

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Figure 5. Chocolate candy intake and the risk of invasive lung cancer in the Women’s Health Initiative. CI ¼ confidence interval;
CL ¼ confidence limit.
consent. The study was conducted in accordance with the
Helsinki Declaration of 1975 as revised in 1989.29
RESULTS
Participant Baseline Characteristics
Sixty-nine percent of the participants reported consuming a 1
oz serving of chocolate more often than monthly (Table 1).
Higher frequency of chocolate intake was associated with (1)
higher BMI, total energy intake, nonchocolate energy intake,
and the Gail Model-2 breast cancer risk indicator and (2) a
higher proportion of participants who were White, had a
high-school diploma or some college education, consumed
an alcoholic drink between once per week and once per day,
were current smokers, had 1 or more close relative who had
had cancer, had previous mammograms, were currently us-
ing female hormones, or had preexisting emphysema.
Conversely, higher frequency of chocolate consumption was
associated with (1) lower levels of physical activity and diet
quality and (2) a lower proportion of participants who were
non-White, had less than a high school diploma, abstained
from alcohol consumption or consumed alcohol more than
once a day, or had preexisting diabetes.
Prospective Association Between Chocolate
Consumption and Invasive Cancer Risk
After all exclusions, there were 96,045, 95,342, 104,845, and
105,374 participants and 16,164, 6038, 1763, and 1965 inci-
dent cases, representing an incidence rate of 17.0, 6.3, 1.9, and
1.7 per 100 participants and 12.3, 4.4, 1.3, and 1.1 per 1000
person years, during a mean follow-up period of 14.7 years
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for uncensored participants in the full-model survival ana-
lyses for total, breast, lung, and colorectal cancer,
respectively.
In the full-model analyses, there were no significant HRs
for total or breast cancer (Table 2 and Figures 2 and 3). There
was a modest significant positive association between choc-
olate intake and the risk of colorectal cancer only for women
who ate a 1 oz (28.4 g) serving of chocolate 1.5 times/wk
(Table 2 and Figure 4). The restricted cubic splines curve
(Figure 4) was not a better fit than the linear curve (P-linear ¼
.02, P-curvature ¼ .03, P for difference ¼ .63). For lung cancer,
the HRs were slightly and significantly lower than 1.0 for
chocolate intakes of <1.5 servings/wk (Table 2 and Figure 5).
The restricted cubic splines curve (Figure 5) was a better fit
than the linear curve (P-linear ¼ .64, P-curvature ¼ .01, P for
difference ¼ .005).
Tests of interaction for BMI in the full-model analyses were
not significant for total (P ¼ .79), breast (P ¼ .51), colorectal
(P ¼ .33), or lung (P ¼ .96) cancer.
Sensitivity and Secondary Analyses
An exploratory analysis was performed with the full model
and the combination of the 13 cancers for which there is
relatively strong evidence that obesity is a risk factor16 as
outcome variable. These cancers are adenocarcinoma of the
esophagus, postmenopausal breast, gallbladder, stomach,
liver, pancreatic, renal, ovarian, uterine, thyroid, and colo-
rectal cancer, as well as meningioma and multiple myeloma.
The results were similar to those for breast cancer in Table 2.
The HR for a first occurrence of 1 of the obesity-related
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Table 1. Baseline characteristicsa of postmenopausal women in different levels of chocolate candy consumption in the Women’s
Health Initiative

Frequency of Consumption of a 1 oz Serving of Chocolate Candy

<1/mo 1 to <0.5/wk 0.5 to <1.5/wk ‡1.5/wk
Characteristics (n [ 30,539) (n [ 19,110) (n [ 24,352) (n [ 24,467)

Variable for predictor ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒmean (SDb)ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ!

Chocolate candy (1 oz servings/d)cd 0.00 (0.01) 0.04 (0.01) 0.11 (0.03) 0.57 (0.48)
Covariates for all cancers
Age (y)cd 64.0 (7.2) 63.7 (7.2) 63.3 (7.2) 63.5 (7.3)
BMIcde 26.8 (5.4) 27.1 (5.3) 27.6 (5.4) 28.0 (5.6)
f cdg
Physical activity (MET h/wk) 14.7 (15.1) 13.7 (14.1) 12.6 (13.3) 11.6 (13.0)
Total dietary energy (kcal/d)cd 1425 (539) 1494 (543) 1633 (574) 1899 (693
Nonchocolate energy (kcal/d)cd 1425 (539) 1489 (543) 1619 (574) 1825 (681)
Alternative Healthy Eating Indexcdh 54.6 (10.6) 53.4 (10.2) 52.3 (10.2) 50.7 (10.4)
Race or ethnicity c
ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ%ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ!
White 80.1 84.7 87.3 89.2
Black 9.9 7.4 6.5 5.1
Hispanic 5.0 3.3 2.3 2.0
Other 5.0 4.5 4.0 3.6
cg
Educational level
<High school 6.0 4.3 3.5 3.6
High school to <college 52.6 52.3 54.0 54.6
College to <postgraduate study 23.0 24.4 23.5 23.5
Postgraduate study or degree 18.4 19.0 19.0 18.3
Alcoholc
Nondrinker 12.3 10.5 9.1 9.7
Former drinker to <1 drink/wk 32.2 28.4 28.3 30.9
1 drink/wk to <1 drink/d 41.5 48.3 49.9 48.9
1 drink/d 14.1 12.8 12.7 10.5
c
Smoking
Never 50.6 51.3 50.2 50.5
Former 43.7 42.6 43.4 42.1
Current 5.7 6.1 6.4 7.4
Covariate for total cancer
Number of close relatives who had
cancerci
0 36.9 36.1 34.9 34.8
1 45.9 46.5 46.8 46.8
2 17.3 17.5 18.3 18.3
Covariates for breast cancer
Mammogram evercd 96.8 97.3 97.4 97.2
ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒmean (SD)ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ!
Gail Model-2 breast cancer riskcdj 1.78 (1.01) 1.79 (1.00) 1.78 (0.99) 1.81 (1.00)
Age at menopause (y) 48.1 (6.4) 48.2 (6.3) 48.2 (6.3) 48.2 (6.3)
(continued on next page)

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Table 1. Baseline characteristicsa of postmenopausal women in different levels of chocolate candy consumption in the Women’s
Health Initiative (continued)

Frequency of Consumption of a 1 oz Serving of Chocolate Candy

<1/mo 1 to <0.5/wk 0.5 to <1.5/wk ‡1.5/wk
Characteristics (n [ 30,539) (n [ 19,110) (n [ 24,352) (n [ 24,467)

Female hormone usec ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ%ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ!

Never 31.5 28.2 28.7 28.9
In the past 22.1 21.5 21.4 22.2
Currently 46.4 50.2 49.9 48.9
i
Number of live births
0 12.8 12.0 12.4 12.9
1-3 60.1 61.2 60.5 59.7
4 27.2 26.8 27.1 27.4
Time breastfeeding (mo)
0 49.1 48.1 49.3 49.5
1-3 37.0 37.9 37.0 36.4
4 13.9 14.0 13.8 14.0
Number of close relatives aged<45 years
who had breast canceri
0 96.8 96.7 96.9 96.7
1 3.0 3.1 3.0 3.2
2 0.2 0.2 0.2 0.2
3 0.0 0.0 0.0 0.0
4 0.0 0.0 0.0 0.0
Covariates for colorectal cancer
Colonoscopy or sigmoidoscopy ever 53.8 54.6 53.8 53.7
Preexisting diabetescd 6.8 3.7 2.6 2.3
Preexisting colitis 1.1 1.1 1.2 1.2
Number of close relatives aged<45 y
who had colorectal cancerg
0 97.0 97.2 97.1 97.1
1-3 3.0 2.8 2.9 2.9
4 0.0 0.0 0.0 0.0
Covariate for lung cancer
Emphysema everc 3.5 3.6 3.7 4.1
a
Data are for observational study and clinical trial control participants with (1) plausible food frequency questionnaire energy intakes, defined as mean intakes <600 kcal/d or >5,000 kcal/d;
BMI (<15 or >50); and height < 122 cm (4 ft) or (2) missing values for any of the characteristics in this table or any outcome variables in our survival analyses.
b
SD ¼ standard deviation.
c
This characteristic showed significant differences between levels of chocolate intake (P < .05) based on analysis of variance, Welch’s analysis of variance, or c2 test. P for trend was <.05 for
all continuous variables except age at menopause. P for trend, based on Cochran-Armitage test, was <.05 for all binary variables, except preexisting colitis and colonoscopy or
sigmoidoscopy ever.
d
P for trend was <.05. For bivariate variables, P for trend was based on the Cochran-Armitage test.
e
BMI ¼ body mass index (measured in kg/m2).
f
MET ¼ metabolic equivalent of task.
g
Educational level and physical activity were quantified by Women’s Health Initiative researchers. Physical activity was total energy expended in recreational physical activity.
h
The Modified Alternative Healthy Eating Index.21
i
Close relatives were defined as mother, father, sister, brother, daughter, or son.
j
Gail Model-2 Breast Cancer Risk22 was calculated by Women’s Health Initiative researchers.

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Table 2. Chocolate intake, HRsa, and 95% CIsb for incidence of different types of invasive cancer in the WHIcd

Frequencye of Chocolate Candy Consumption (1 oz Servings) P-linear /

Covariates in the model <1/mof 1/mo to <0.5/wk 0.5/wk to <1.5/wk ‡1.5/wk Total P-curvatureg

First occurrence of invasive

total cancer
Age, race or ethnicity, and .03 / .02
WHI study arm
HR (95% CI)h 1.00 0.99 (0.94-1.03) 1.03 (0.99-1.07) 1.04 (1.00-1.08)
i
No. of women 31,164 19,340 24,717 24,883 100,104
No. of eventsi 5,062 3,226 4,337 4,428 17,053
j
Full model .47 / .14
HR (95% CI) 1.00 0.98 (0.94-1.03) 1.02 (0.97-1.06) 1.01 (0.97-1.06)
No. of women 29,696 18,356 23,492 23,502 95,046
No. of events 4,814 3,053 4,136 4,161 16,164
First occurrence of invasive
breast cancer
Age, race or ethnicity, and
WHI study arm
HR (95% CI) 1.00 1.01 (0.94-1.08) 1.04 (0.98-1.11) 1.03 (0.97-1.10) .37 / .22
No. of women 33,433 20,765 26,493 26,663 107,354
No. of events 1,980 1,291 1,733 1,726 6,730
Full model .77 / .26
HR (95% CI) 1.00 0.98 (0.91-1.06) 1.02 (0.96-1.10) 0.99 (0.92-1.06)
No. of women 29,559 18,504 23,606 23,673 95,342
No. of events 1,770 1,156 1,570 1,542 6,038
First occurrence of invasive
colorectal cancer
Age, race or ethnicity, and .003 / .01
WHI study arm
HR (95% CI) 1.00 1.08 (0.94-1.23) 1.07 (0.94-1.21) 1.21 (1.07-1.36)
No. of women 35,149 21,757 27,609 27,869 112,384
No. of events 537 364 459 527 1,887
Full model .02 / .03
HR (95% CI) 1.00 1.08 (0.94-1.24) 1.07 (0.94-1.22) 1.18 (1.04-1.35)
No. of women 32,823 20,289 25,835 25,898 104,845
No. of events 501 337 432 493 1,763
First occurrence of invasive
lung cancer
Age, race or ethnicity, and .63 / .02
WHI study arm
HR (95% CI) 1.00 0.81 (0.71-0.92) 0.90 (0.81-1.01) 0.95 (0.85-1.07)
No. of women 34,994 21,688 27,614 27,836 112,132
No. of events 677 353 510 548 2,088
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Table 2. Chocolate intake, HRsa, and 95% CIsb for incidence of different types of invasive cancer in the WHIcd (continued)

Frequencye of Chocolate Candy Consumption (1 oz Servings) P-linear /

Covariates in the model <1/mof 1/mo to <0.5/wk 0.5/wk to <1.5/wk ‡1.5/wk Total P-curvatureg

Full model .64 / .01

HR (95% CI) 1.00 0.79 (0.69-0.90) 0.87 (0.78-0.99) 0.90 (0.80-1.01)
No. of women 32,958 20,375 26,000 26,041 105,374
No. of events 642 330 479 514 1,965
a
HR ¼ hazard ratio.
b
CI ¼ confidence interval.
c
WHI ¼ Women’s Health Initiative.
d
The analytic sample included observational study and clinical trial control participants with nonextreme self-reported dietary energy intake (600 and 5,000 kcal/d), body mass index
(15 and 50) and height (122 cm or 4 ft).
e
Frequency of chocolate intake was assessed by means of a semiquantitative food frequency question.
f
Referent chocolate consumption category.
g
P-linear was calculated using the median frequency of chocolate intake in each quartile as sole predictor in the model. P-curvature was the significance level of the restricted cubic splines
curve for the hazard ratio and chocolate intake.
h
HR (95% CI) determined by means of Cox regression.
i
No. of women at year 0 (baseline), the number of participants without preexisting cancer of the type in the outcome at year 0 who provided data on all variables at year 0. No. of events, the
number of new cases of the type of cancer in the outcome during the follow-up period for patients who were uncensored for the type of cancer in the outcome.
j
Full models were adjusted for the following covariates: age; race or ethnicity status (White, Black, Hispanic, other); WHI study arm (observational study and clinical trial control); smoking
status (never, past, <15/d, 15/d); total recreational energy expended in metabolic equivalent of task hours per week (includes walking; mild, moderate, and strenuous physical activity);
Alternative Health Eating Index 21; alcohol intake; education to <high school, some high school to <college, some college to <postgraduate study, postgraduate study or degree. Full
models were also adjusted for additional covariates for the following site-specific cancers: (1) total cancer—close relatives with a history of any type of cancer (0 ¼ no, 1 ¼ 1 male or female
relative, 2 ¼ both a male and female relative); (2) breast cancer—total months breast fed children (0-6), number of live births (0-7, 8þ), female hormone usage (0 ¼ never, 1 ¼ in the past,
2 ¼ current), previous mammograms (yes or no), close relatives with age <45 y and a history of breast cancer (0-5); age at menopause (20-60 y) and a Gail Model 2 variable,22 which
replaced age and race or ethnicity; (3) colorectal cancer—number of close female or male relatives diagnosed with colorectal cancer before the age of 45 y (0-5), prior colonoscopy or
sigmoidoscopy (yes or no), preexisting diabetes (yes or no) or preexisting ulcerative colitis or Crohn’s disease (yes or no); and (4) lung cancer—preexisting emphysema (yes or no).

cancers was 1.00 for a 1 oz serving of chocolate <1 time/mo,
0.99 (95% CI: 0.93-1.05) for 1 time/mo to <0.5 times/wk, 1.04
(95% CI: 0.98-1.09) for 0.5 to <1.5 times/wk, and 1.01 (95% CI:
0.96-1.07) for 1.5 times/wk (P-linear ¼.67, P-curvature ¼ .55,
P for difference ¼ .41).
The full-model analyses in Table 2 were repeated after
adding BMI as a covariate due to its potential role as a
mediator variable for the 2 cancers for which excess adiposity
is an established risk factor—breast and colorectal cancer. A
similar exploratory analysis was performed for the combined
obesity-related cancers. All 9 of the nonreferent HRs showed
a change in the second or third decimal place, which brought
them closer to the null value of 1.0. (See Table 3, available at
www.jandonline.org.)
Time-dependent Cox regression was used in the full-model
analyses in Table 2 as an exploratory analysis to assess the
effect of updating the predictor at year 3, when the WHI FFQ
was readministered. The results were very similar to those in
Tables 2. (See Table 4, available at www.jandonline.org.)
The full-model analyses in Table 2 were repeated after
adding participants in the 3 WHI CT intervention groups to
our analytic sample. The purpose was to explore the effects of
including these participants in the survival analyses. The re-
sults were similar to those in Table 2, except that there were
fewer significant HRs for the analyses for colorectal and lung
cancer. (See Table 5, available at www.jandonline.org.)
DISCUSSION
This prospective analysis of data from postmenopausal
women in the WHI cohort yielded a weak positive association
between chocolate candy consumption and invasive colo-
rectal cancer among women who ate chocolate most
frequently. The increased risk of incidence of colorectal can-
cer was 18% (95% CI: 4%-35%) for women who consumed a 1
oz serving 1.5 times/wk. This positive association was
robust in that it was also observed in 3 exploratory sensitivity
analyses. Given that adiposity is an established risk factor for
colorectal cancer,16 this result may be attributable to the
excess adiposity associated with frequent chocolate candy
consumption in WHI participants.30 Supporting this idea is
the fact that WHI participants who were more frequent
consumers of chocolate also consumed more dietary energy
and food of lower dietary quality (see Table 1).
Two previously published case-control studies of the as-
sociation between chocolate consumption among adults and
the risk of colorectal cancer were identified. The first study by
McKelvey et al12 focused on American adults between the
ages of 30 and 89. There was no significant association be-
tween chocolate candy intake and the prevalence of colo-
rectal adenomas in their second or third tertile of intake
when compared with their first tertile. This result conflicts
with the finding here of a significant positive association in
the fourth quartile among WHI women when compared with
the first quartile. On the other hand, the second study, by
Boutron-Ruault et al14 did find an elevated risk of colorectal
cancer among women (and men) in their third quartile of
chocolate intake in French adults between the age of 30 and
79 years. This result is similar to the present finding, and
French and American per-capita chocolate candy consump-
tion was similar in the 1990s31 when Boutron-Ruault and the
WHI assessed chocolate intake among their participants.

February 2021 Volume 121 Number 2 JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS 323
RESEARCH
However, French and American chocolate candy in the 1990s
may have contained different concentrations of ingredients
that can affect the risk of colorectal cancer. Hence, it is
possible that the present significant finding is due to residual
confounding.
The weak inverse association between chocolate intake
and the risk of lung cancer at intake between monthly and
<1.5 times/wk is not consonant with the results from Arts
et al,13 who used data from 738 men in the prospective
Zutphen Elderly Study. They found that an increase in
chocolate consumption equivalent to a 7.5 mg/d increase in
catechin intake was associated with a nonsignificant 24%
decrease in risk of lung cancer. The present analysis
showed 21% and 13% significant decreases in risk of lung
cancer for chocolate intake in the second and third quar-
tiles, respectively, of chocolate intake, with the first quartile
of intake as referent. It is difficult to compare the present
results with those of Arts et al because Arts et al did not
assess relative risks in different categories of intake. Also,
the large sample size in the WHI enabled calculation of
relative risks in different quartiles and assessment of cur-
vature in the association. These differences may explain
why the result in this study was significant and the result
in the study by Arts et al was not. However, a literature
search did not yield empirical evidence to cogently explain
the ability of intake of 1 oz of chocolate candy <1.5 times/
wk to reduce the risk of lung cancer. It seems likely,
therefore, that residual confounding accounts for the pre-
sent significant outcome.
This study has several strengths. The WHI data were
carefully collected, edited, and validated with the use of
current, empirically based techniques,17,32 and cancer end
points were rigorously adjudicated. Second, the data set is
large enough to have provided adequate statistical power and
a rich variety of important confounder variables for the an-
alyses reported here.
This study also has several limitations. First, this study
was an observational study. It is therefore possible that its
significant findings were due to residual confounding. Long-
term randomized human trials are needed to more rigor-
ously account for confounding in the association between
chocolate or cocoa flavonoid consumption and cancer risk.
Second, the chocolate-intake variable was derived from self-
reported answer to a single FFQ question, and FFQ data18 are
subject to measurement error33 that can distort HR
estimates.34 In this regard, the present sensitivity analysis
with time-dependent Cox regression using an average of 2
assessments of the exposure variable 3 years apart produced
evidence suggesting that regression-dilution effects were
not large enough to invalidate the results of this study.
Third, the WHI FFQ did not request information on the type
of chocolate consumed by WHI participants. The concen-
tration of chocolate, cocoa, energy, added sugars, and fat
was not assessed and is likely to be different in different
types and brands of chocolate and chocolate candy.35 Simi-
larly, the concentration of cocoa and flavonoids varies
greatly in different types of chocolate.36 Hence, the present
analysis was unable to explore the potential effects of these
factors. Future studies should include, and assess the effects
of, constituents such as energy, fats, added sugars, and cocoa
compounds including flavanols and flavonols in the
consumed chocolate.
324 JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS
CONCLUSIONS
The analysis of data from the prospective WHI cohort showed
no significant association between intake of chocolate candy
and the risk of invasive total or breast cancer. There was a
modest 18% higher risk of invasive colorectal cancer for
women who ate chocolate candy relatively frequently (1.5
times/wk). This result could be due to residual confounding.
More rigorous controlled prospective trials are needed to test
the validity of these findings.
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16. Lauby-Secretan B, Scoccianti C, Loomis D, et al. Body fatness and
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17. WHI Study Group. Design of the Women’s Health Initiative clinical
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21. Chiuve SE, Fung TT, Rimm EB, et al. Alternative dietary indices both
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JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS 325
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AUTHOR INFORMATION
J. A. Greenberg is an emeritus professor, Department of Health and Nutrition Sciences, Brooklyn College of the City University of New York,
Brooklyn. M. L. Neuhouser is the program head and L. F. Tinker is a nutrition scientist, Division of Public Health Sciences, Fred Hutchinson Cancer
Research Center, Seattle, WA. D. S. Lane is a distinguished service professor and vice chair, Department of Family, Population and Preventive
Medicine, School of Medicine, Stony Brook University, Stony Brook, NY. E. D. Paskett is a Marion N. Rowley professor of cancer research,
Department of Internal Medicine, Division of Cancer Prevention and Control, College of Medicine, Comprehensive Cancer Center, and S. Sealy-
Jefferson is an assistant professor, Division of Epidemiology, College of Public Health, both at Ohio State University, Columbus, OH. L. V. Van Horn
is the chief of nutrition, Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL. S. Wassertheil-
Smoller is a distinguished university professor emerita, Department of Epidemiology and Population Health, Albert Einstein College of Medicine,
Bronx, NY. J. M. Shikany is an endowed professor of cardiovascular disease and associate director for research, Division of Preventive Medicine,
School of Medicine, University of Alabama at Birmingham. L. Qi is a professor, Department of Public Health Sciences, School of Medicine,
University of California Davis. J. E. Manson is a professor, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School,
Boston, MA.
Address correspondence to: James A. Greenberg, PhD, Department of Health & Nutrition Sciences, Brooklyn College of the City University of New
York, 2900 Bedford Ave, Brooklyn, NY 11201. E-mail: jamesg@brooklyn.cuny.edu
STATEMENT OF POTENTIAL CONFLICT OF INTEREST
J. E. Manson and colleagues at Brigham and Women’s Hospital, Harvard Medical School are recipients of funding from Mars Symbioscience for an
investigator-initiated randomized trial of cocoa flavanols and chronic disease outcomes. No potential conflict of interest was reported by the
other authors.
FUNDING/SUPPORT
The Women’s Health Initiative (WHI) program is funded by National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI),
US Department of Health and Human Services through contracts HHSN268201600018C, HHSN268201600001C, HHSN268201600002C,
HHSN268201600003C, and HHSN268201600004C. In addition, the following authors had funding related to this project: J. E. Manson had partial
support from HHSN268201100001C from NIH/NHLBI, the Women’s Health Initiative program. J. E. Manson and colleagues at Brigham and
Women’s Hospital, Harvard Medical School are recipients of funding from Mars Symbioscience for an investigator-initiated randomized trial of
cocoa flavanols and chronic disease outcomes. L. F. Tinker and M. L. Neuhouser received support from NIH/NHLBI, US Department of Health and
Human Services contract HHSN268201100046C. D. S. Lane received support from Stony Brook WHI Center grant, NHLBI contract no. NO1-WH-4-
2115.
ACKNOWLEDGEMENTS
Many thanks to the WHI Investigators (see the Appendix, available at www.jandonline.org) for their efforts in the collection of the WHI data.

AUTHOR CONTRIBUTIONS
J. A. Greenberg, J. E. Manson, and L. Qi designed the research. J. A. Greenberg analyzed the data. J. A. Greenberg, J. E. Manson, L. F. Tinker, J. M.
Shikany, and M. L. Neuhouser interpreted data. J. A. Greenberg wrote the paper and had primary responsibility for final content. J. A. Greenberg,
J. E. Manson, L. F. Tinker, M. L. Neuhouser, D. S. Lane, E. D. Paskett, L. V. Van Horn, S. Wassertheil-Smoller, S. Sealy-Jefferson, J. M. Shikany, and L. Qi
read, edited, and approved the final manuscript before submission.

326 JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS February 2021 Volume 121 Number 2
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Table 3. Chocolate intake, HRsa, and 95% CIsb for incidence of invasive breast, colorectal and the other 11 obesity-related
cancers with body mass index as a covariate in the Women’s Health Initiativec

Frequencyd of Chocolate Candy Consumption (1 oz Servings)

Covariates in the model <1/moe 1/mo to <0.5/wk 0.5/wk to <1.5/wk ‡1.5/wk Total

First occurrence of an invasive

obesity-related cancer
Full modelf
HR (95% CI)g 1.00 0.99 (0.93-1.05) 1.03 (0.97-1.09) 1.01 (0.95-1.06)
No. of womenh 29,696 18,356 23,492 23,502 95,046
h
No. of events 2,814 1,804 2,459 2,429 9,506
First occurrence of invasive breast
cancer
Full model
HR (95% CI) 1.00 0.99 (0.93-1.05) 1.02 (0.95-1.09) 0.98 (0.91-1.05)
No. of women 29,559 18,504 23,606 23,673 95,342
No. of events 1,770 1,156 1,570 1,542 6,038
First occurrence of invasive
colorectal cancer
Full model
HR (95% CI) 1.00 1.07 (0.93-1.23) 1.06 (0.93-1.21) 1.17 (1.02-1.33)
No. of women 32,823 20,289 25,835 25,898 104,845
No. of events 501 337 432 493 1,763
a
HR ¼ hazard ratio.
b
CI ¼ confidence interval.
c
The analytic sample included observational study and clinical trial control participants with nonextreme self-reported dietary energy intake (600 and 5000 kcal/d), body mass index
(15 and 50 kg/m2) and height (122 cm or 4 ft).
d
Frequency of chocolate intake was assessed by means of a semiquantitative food frequency question.
e
Referent chocolate consumption category.
f
Full models were adjusted for the following covariates: age; body mass index; race or ethnic status (White, Black, Hispanic, other); Women’s Health Initiative study arm (observational study
and clinical trial control); smoking status (never, past, <15/d, 15/d); total recreational energy expended in metabolic equivalent of task hours per week (includes walking; mild, moderate,
and strenuous physical activity); Alternative Health Eating Index21; alcohol intake; education (<high school, some high school to <college, some college to <postgraduate study,
postgraduate study or degree). Full models were also adjusted for additional covariates for the following site-specific cancers: (1) total cancer—close relatives with a history of any type of
cancer (0 ¼ no, 1 ¼ 1 male or female relative, 2 ¼ both a male and female relative); (2) breast cancer—total months breastfed children (0-6), number of live births (0-7, 8þ), female
hormone usage (0 ¼ never,1 ¼ in the past, 2 ¼ current), previous mammograms (yes or no), close relatives with age <45 y and a history of breast cancer (0-5), age at menopause (20-60
y), and a Gail Model 2 variable,22 which replaced age and race or ethnicity; (3) colorectal cancer—number of close female or male relatives diagnosed with colorectal cancer before the age
of 45 y (0-5), prior colonoscopy or sigmoidoscopy (yes or no), preexisting diabetes (yes or no) or preexisting ulcerative colitis or Crohn’s disease (yes or no); and 4) lung cancer—preexisting
emphysema (yes or no).
g
HR (95% CI) determined by means of Cox regression.
h
No. of women at year 0 (baseline), the number of participants without preexisting cancer of the type in the outcome at year 0 who provided data on all variables at year 0. No. of events,
the number of new cases of the type of cancer in the outcome during the follow-up period for patients who were uncensored for the type of cancer in the outcome.

February 2021 Volume 121 Number 2 JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS 326.e1
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Table 4. Chocolate intake, time-dependent covariate HRsa, and 95% CIsb for incidence of different types of invasive cancer in
the Women’s Health Initiativec

Frequencyd of Chocolate Candy Consumption (1 oz Servings)

Covariates in the model <1/moe 1/mo to <0.5/wk 0.5/wk to <1.5/wk ‡1.5/wk Total

First occurrence of invasive total cancer

Full modelf 1.00 1.01 (0.97-1.06) 1.02 (0.98-1.07) 1.02 (0.98-1.07)
g
HR (95% CI)
No. of womenh 29,696 18,356 23,492 23,502 95,046
h
No. of events 4,814 3,053 4,136 4,161 16,164
First occurrence of invasive breast cancer
Full model
HR (95% CI) 1.00 1.06 (0.99-1.14) 1.01 (0.94-1.08) 1.01 (0.94-1.09)
No. of women 29,559 18,504 23,606 23,673 95,342
No. of events 1,770 1,156 1,570 1,542 6,038
First occurrence of invasive colorectal cancer
Full model
HR (95% CI) 1.00 1.00 (0.87-1.16) 1.07 (0.94-1.22) 1.14 (1.00-1.30)
No. of women 32,823 20,289 25,835 25,898 104,845
No. of events 501 337 432 493 1,763
First occurrence of invasive lung cancer
Full model
HR (95% CI) 1.00 0.83 (0.73-0.95) 0.89 (0.78-1.00) 0.91 (0.80-1.02)
No. of women 32,958 20,375 26,000 26,041 105,374
No. of events 642 330 479 514 1,965
a
HR ¼ hazard ratio.
b
CI ¼ confidence interval.
c
The analytic sample included observational study and clinical trial control participants with nonextreme self-reported dietary energy intake (600 and 5000 kcal/d), body mass index
(>15 and <50 kg/m2), and height (>122 cm or >4 ft).
d
Frequency of chocolate intake was assessed by means of a semiquantitative food frequency question.
e
Referent chocolate consumption category.
f
Full models were adjusted for the following covariates: age; race or ethnic status (White, Black, Hispanic, other); Women’s Health Initiative study arm (observational study and clinical trial
control); smoking status (never, past, <15/d, 15/d); total recreational energy expended in metabolic equivalent of task hours per week (includes walking; mild, moderate, and strenuous
physical activity); Alternative Health Eating Index21; alcohol intake; education (<high school, some high school to <college, some college to <postgraduate study, postgraduate study or
degree). Full models were also adjusted for additional covariates for the following site-specific cancers: (1) total cancer—close relatives with a history of any type of cancer (0 ¼ no, 1 ¼ 1
male or female relative, 2 ¼ both a male and female relative); (2) breast cancer—total months breastfed children (0-6), number of live births (0-7, 8þ), female hormone usage (0 ¼
never,1 ¼ in the past, 2 ¼ current), previous mammograms (yes or no), close relatives with age <45 y and a history of breast cancer (0-5), age at menopause (20-60 y), and a Gail Model 2
variable,22 which replaced age and race or ethnicity; (3) colorectal cancer—number of close female or male relatives diagnosed with colorectal cancer before the age of 45 y (0-5), prior
colonoscopy or sigmoidoscopy (yes or no), preexisting diabetes (yes or no) or preexisting ulcerative colitis or Crohn’s disease (yes or no); and (4) lung cancer—preexisting emphysema (yes
or no).
g
HR (95% CI) determined by means of Cox regression.
h
No. of women at year 0 (baseline), the number of participants without preexisting cancer of the type in the outcome at year 0 who provided data on all variables at year 0. No. of events,
the number of new cases of the type of cancer in the outcome during the follow-up period for patients who were uncensored for the type of cancer in the outcome.

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Table 5. Chocolate intake, covariate HRsa, and 95% CIsb for incidence of different types of invasive cancer, with all clinical trial
participants in the Women’s Health Initiativec

Frequencyd of Chocolate Candy Consumption (1 oz Servings)

Covariates in the model <1/moe 1/mo to <0.5/wk 0.5/wk to <1.5/wk ‡1.5/wk Total

First occurrence of invasive total cancer

Full modelf 1.00 0.99 (0.95-1.03) 1.03 (0.99-1.06) 1.01 (0.98-1.05)
g
HR (95% CI)
No. of womenh 38,173 24,415 32,716 33,743 129,047
h
No. of events 6,211 4,119 5,830 6,032 22,192
First occurrence of invasive breast cancer
Full model
HR (95% CI) 1.00 1.01 (0.94-1.07) 1.05 (0.99-1.12) 1.00 (0.94-1.07)
No. of women 37,691 24,378 32,593 33,770 128,432
No. of events 2,219 1,534 2,191 2,206 8,150
First occurrence of invasive colorectal cancer
Full model
HR (95% CI) 1.00 1.06 (0.94-1.19) 1.03 (0.92-1.15) 1.11 (1.00-1.25)
No. of women 41,520 26,519 35,294 36,472 139,805
No. of events 676 462 606 692 2,436
First occurrence of invasive lung cancer
Full model
HR (95% CI) 1.00 0.82 (0.73-0.92) 0.94 (0.84-1.04) 0.93 (0.84-1.03)
No. of women 41,634 26,584 35,438 36,596 140,252
No. of events 809 439 683 720 2,651
a
HR ¼ hazard ratio.
b
CI ¼ confidence interval.
c
The analytic sample included observational study and all clinical trial participants with nonextreme self-reported dietary energy intake (600 and 5000 kcal/d), body mass index (>15
and <50 kg/m2), and height (>122 cm or >4 ft).
d
Frequency of chocolate intake was assessed by means of a semiquantitative food frequency question.
e
Referent chocolate consumption category.
f
Full models were adjusted for the following covariates: age; race or ethnic status (White, Black, Hispanic, other); Women’s Health Initiative study arm (observational study, clinical trial control
and the 10 different combinations of clinical trials in which the women participated); smoking status (never, past, <15/d, 15/d); total recreational energy expended in metabolic
equivalent of task hours per week (includes walking; mild, moderate, and strenuous physical activity); Alternative Health Eating Index21; alcohol intake; education (<high school, some high
school to <college, some college to <postgraduate study, postgraduate study or degree). Full models were also adjusted for additional covariates for the following site-specific cancers:
(1) total cancer—close relatives with a history of any type of cancer (0 ¼ no, 1 ¼ 1 male or female relative, 2 ¼ both a male and female relative); (2) breast cancer—total months breastfed
children (0-6), number of live births (0-7, 8þ), female hormone usage (0 ¼ never, 1 ¼ in the past, 2 ¼ current), previous mammograms (yes or no), close relatives with age <45 y and a
history of breast cancer (0-5), age at menopause (20-60 y), and a Gail Model 2 variable,22 which replaced age and race or ethnicity; (3) colorectal cancer—number of close female or male
relatives diagnosed with colorectal cancer before the age of 45 y (0-5), prior colonoscopy or sigmoidoscopy (yes or no), preexisting diabetes (yes or no), or preexisting ulcerative colitis or
Crohn’s disease (yes or no); and (4) lung cancer—preexisting emphysema (yes or no).
g
HR (95% CI) determined by means of Cox regression.
h
No. of women at year 0 (baseline), the number of participants without preexisting cancer of the type in the outcome at year 0 who provided data on all variables at year 0. No. of events,
the number of new cases of the type of cancer in the outcome during the follow up period for patients who were uncensored for the type of cancer in the outcome.

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RESEARCH

APPENDIX. WOMEN’S HEALTH INITIATIVE INVESTIGATORS

Title of Publication: Chocolate Candy and Incident Invasive Cancer Risk in the Women’s Health Initiative: An Observational
Prospective Analysis
Authors: James A. Greenberg1, Marian L. Neuhouser2, Lesley F. Tinker3, Dorothy S. Lane4, Electra D. Paskett5, Linda V. Van
Horn6, Sylvia Wassertheil-Smoller7, James M. Shikany8, Lihong Qi9, Shawnita Sealy-Jefferson10, JoAnn E. Manson11
Affiliations: (1) Department of Health and Nutrition Sciences, Brooklyn College of the City University of New York, Brooklyn,
NY; (2) Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA; (3) Division of Public Health
Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA; (4) Department of Family, Population and Preventive Medicine,
School of Medicine, Stony Brook University, Stony Brook, NY; (5) Division of Cancer Prevention and Control, Department of
Internal Medicine, College of Medicine; Comprehensive Cancer Center, The Ohio State University, Columbus, OH; (6) Depart-
ment of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL; (7) Department of Epidemi-
ology and Population Health, Albert Einstein College of Medicine, Bronx, NY; (8) Division of Preventive Medicine, School of
Medicine, University of Alabama at Birmingham, AL; (9) Department of Public Health Sciences, School of Medicine, University of
California Davis, Davis, CA; (10) Division of Epidemiology, College of Public Health, Ohio State University, Columbus, OH; (11)
Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA.

Short List of Women’s Health Initiative Investigators

Program Office: National Heart, Lung, and Blood Institute, Bethesda, Maryland: Jacques Rossouw, Shari Ludlam, Dale Burwen,
Joan McGowan, Leslie Ford, and Nancy Geller
Clinical Coordinating Center: (Fred Hutchinson Cancer Research Center, Seattle, WA) Garnet Anderson, Ross Prentice, Andrea
LaCroix, and Charles Kooperberg
Investigators and Academic Centers: (Brigham and Women’s Hospital, Harvard Medical School, Boston, MA) JoAnn E. Manson;
(MedStar Health Research Institute/Howard University, Washington, DC) Barbara V. Howard; (Stanford Prevention Research
Center, Stanford, CA) Marcia L. Stefanick; (The Ohio State University, Columbus, OH) Rebecca Jackson; (University of Arizona,
Tucson/Phoenix, AZ) Cynthia A. Thomson; (University at Buffalo, Buffalo, NY) Jean Wactawski-Wende; (University of Florida,
Gainesville/Jacksonville, FL) Marian Limacher; (University of Iowa, Iowa City/Davenport, IA) Robert Wallace; (University of
Pittsburgh, Pittsburgh, PA) Lewis Kuller; (Wake Forest University School of Medicine, Winston-Salem, NC) Sally Shumaker
Women’s Health Initiative Memory Study: (Wake Forest University School of Medicine, Winston-Salem, NC) Sally Shumaker
For a list of all the investigators who have contributed to Women’s Health Initiative science, please visit: https://www.whi.
org/researchers/Documents%20%20Write%20a%20Paper/WHI%20Investigator%20Long%20List.pdf.

326.e4 JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS February 2021 Volume 121 Number 2