C H A P T E R
19
Dietary Assessment
CATHERINE L. CARPENTER
INTRODUCTION
Over the past 25 years, dietary assessment methodology
has made significant progress in identifying associations
between patterns of dietary consumption and cancer risk.
Although it is not yet possible to quantify specific cancer
risks related to specific foods or dietary patterns, there is
considerable evidence that certain foods are associated with
increased cancer risk. For example, epidemiological studies
have identified a clear association of increased red meat
intake with an increased risk for colorectal cancer (Chao
et al., 2005; Willett, 2005).
The choice of optimal dietary assessment methods
depends on the research question being asked, the cancer site
under study, the research study design, and the metabolic/
biochemical measurements available for characterizing
dietary intake. Moreover, factors intrinsic to the dietary
assessment instruments have been shown to affect the results
obtained. These include the quality of nutrient and food com-
position databases, the sensitivity of specific assessment
instruments to differences in nutrient intake, and the flexibil-
ity of the assessment instrument for diverse dietary intakes. A
number of these methodological constraints that can lead to
inconsistent results on the association of diet and cancer risk
have appeared in published studies from different groups of
investigators.
STUDY DESIGN AND ASSESSMENT
Dietary Pattern Assessment
Measurements of dietary patterns are generally conducted
using recall methods (Tarasuk and Brooker, 1997). Recall of
subjects’ dietary histories are meant to approximate dietary
Nutritional Oncology
exposures before cancer induction. Because cancer tends to
develop very slowly over a 20–30 year period, memories of
subjects’ diets long ago are often inaccurate.
Recall bias can occur for many reasons. One example of
recall bias is reporting of dietary intake by obese subjects,
which is different from reporting of dietary habits by lean
subjects. Many obese subjects omit mentioning those foods
they know they should not be eating. Patients suffering from
cancer malnutrition may be weakened, or even cachectic, so
their ability to recall foods may be impaired in comparison
to healthy controls. Controls reporting higher consumption
with a particular food relative to cases that are cachectic may
distort associations toward a preventive or risk-enhancing
direction, leading to false conclusions.
Prospective Longitudinal Study Designs
The major advantage of conducting a prospective cohort
study is measurement of dietary intake before disease onset,
which can provide important insight into causal relation-
ships between dietary patterns and cancer. However, deter-
mination of the relevant etiological time period for dietary
assessment can be challenging (Tarasuk and Brooker, 1997).
Major disadvantages for conducting a prospective cohort
study include lengthy time of study, large sample sizes
required to detect associations with rare cancer outcomes,
the higher costs associated with subject recruitment and
measurement over time, and specialized composition of
cohorts that limit generalizability.
Nutrigenetics and Nutrigenomics
Genetic and molecular epidemiological study designs
such as case–case and gene-association studies are
Copyright © 2006, Elsevier Inc.
367 All rights of reproduction in any form reserved.
368 Chapter 19/Dietary Assessment
beginning to evaluate interactions between dietary intake
and genetic polymorphisms, as well as interactions between
dietary intake and gene expression. Genetic polymorphisms
are a function of inheritance and can be considered fixed
exposures over the lifetime, whereas gene expression and
epigenetic changes vary over the lifetime.
Both acquired genetic changes and inherited susceptibil-
ity, coupled with environmental exposures, are responsible
for development of cancer. The technology for measuring
gene expression and epigenetic changes such as DNA
methylation in relationship to nutritional intake and cancer
has only been developed recently. A study of DNA methy-
lation of gastric tumors was conducted among 58 male
patients who completed food frequency questionnaires
(FFQs) and lifestyle questionnaires. Tumors were catego-
rized according to methylation status, and dietary factors
were compared in relationship to methylation. The study
found an association between CDX2 gastric tumor methy-
lation and decreased intake of green tea and cruciferous veg-
etables (Yuasa et al., 2005).
Gene-association studies examine relationships between
polymorphisms of inherited genes, environmental expo-
sures, and risk of disease. Dietary intake and gene associa-
tion studies in relationship to cancer risk can be conducted
prospectively or retrospectively, using cross-sectional,
case-control, or prospective cohort designs. One example is
a report of serum biomarkers of carotenoids that were studied
in relationship to DNA repair gene (XRCC1) haplotypes and
breast cancer risk in the Nurses’ Health Study (Han et al.,
2003). The study found a marginally significant reduction in
breast cancer risk among women who carried at least one
194Trp allele compared wtih noncarriers. One of the haplo-
types of the XRCC1 gene, Arg194Trp, modified the inverse
associations of plasma α-carotene level and plasma β-
carotene level with breast cancer risk (Han et al., 2003).
METHODS OF DIETARY ASSESSMENT
Dietary assessment is used to identify and monitor types
and amounts of foods and beverages consumed by individ-
uals and groups of individuals. Results of dietary assess-
ments, in turn, shape public health policy and programs.
Identifying dietary patterns or food constituents that clearly
contribute to or prevent development of cancer is a primary
goal and challenge of diet and cancer research.
Accurate estimation of nutritional intake is fundamental
to studies of diet and cancer. Various methods exist for
assessment of dietary intake in free-living individuals. The
three main approaches are 24-hour recalls, diet records, and
FFQs. Both 24-hour recalls and diet records allow for free-
form open-ended recording of food intake. FFQs have pre-
assigned lists of foods and set categories for amount of food
consumed.
An ideal dietary assessment instrument should provide an
accurate, objective, unbiased, and quantitative measure of
long-term exposure to dietary constituents. The accuracy
of dietary assessment depends, in part, on the accuracy of
available food composition data; the need for expanded
composition data for commonly eaten foods is widely rec-
ognized. Epidemiological surveys, controlled feeding, meta-
bolic studies, and clinical trials of dietary modification all
use dietary assessment methods.
The general-purpose instruments used to estimate nutri-
ent intake in populations are not well suited to assessing the
modest dietary changes that might result from a dietary
intervention. Even within an intervention, different instru-
ments might be used for assessment at baseline versus after
intervention because of significant changes in consumption
and food preparation techniques.
Controlled feeding and metabolic studies, in which all
foods are provided, permit close monitoring of food and
nutrient intake, as well as biological and metabolic
responses that result from dietary change. Such studies
are important for development of validated standardized
nutritional biomarkers, which may be useful adjuncts to
traditional dietary assessment instruments. Selection of
the dietary survey methodology, among other things, is
dependent on the study design and timing of dietary expo-
sure measurement (Barrett-Connor, 1991; Sempos et al.,
1999).
Twenty-four Hour Recall
Twenty-four hour recalls ask individuals to describe, in
either an in-person or telephone interview with a nutrition-
ist or trained interviewer, what they have eaten during the
previous 24 hours (Willett et al., 1985; World Cancer
Research Fund [WCRF], 1997).
This method has the advantages of requiring minimal
effort on the part of the study participant (Willett, 1987).
Although single 24-hour recalls are highly accurate and reli-
able measures of recent intake, they do not account for day-
to-day variability in an individual’s diet and generally are
not recommended for use in longitudinal large-scale cohort
studies (Willett et al., 1985; Willett, 1987; WCRF, 1997).
On the other hand, 24-hour recall methods have better reli-
ability for assessing current and immediate dietary patterns
for validation of biomarkers that characterize the intake of
particular nutrients, as well as assessing dietary compliance
in dietary intervention studies.
Using data from a carefully designed validation study
conducted by Willett et al. (1985), Byar and Freedman
(1989) argue that one reason the precision of subjective
dietary assessment methods such as FFQs and dietary
records is limited or compromised is that individuals are not
aware of what they eat. Willett’s validation study included
173 female nurses who were asked to record everything they
 Methods of Dietary Assessment
ate for 7 days on four separate occasions ~3 months apart.
The same subjects also completed a semiquantitative FFQ
on two separate occasions. In this case, the dietary food
records served as the “gold standard” against which the
questionnaire data were validated.
Quintiles of intake from the FFQ were then cross-
classified with quintiles from the 7-day food records. If the
two methods were measuring the same intakes with no
measurement error, a one-to-one direct correlation (a corre-
lation of 1) between the same quintiles of intake would
result. Interestingly, however, only 53% of individuals in the
first quintile for the questionnaire data also were in the first
quintile for the food record data. Correlations were even
lower for the other quintile comparisons. Such data provide
insight into how well, or poorly, one assessment method
compares with another. Whether participants actually
provide different dietary profiles in the different instruments,
or whether questionnaires and recall methods do not
adequately match items described in personal food diaries,
warrants further investigation.
The new multiple-pass method for collecting 24-hour
dietary recalls maintains related systems and databases and
is designed to engage the respondent more completely to
provide more accurate recalls than earlier methods (Dwyer
et al., 2001). These types of 24-hour recalls have been con-
sistently used to characterize food intakes of large popula-
tion groups such as those surveyed in the National Health
and Nutrition Examination Survey (NHANES) (U.S.
Department of Health and Human Services, 2005). The Con-
tinuing Survey of Food Intakes by Individuals (CSFII) and
the NHANES have become integrated (Dwyer et al., 2001).
The integrated survey has been administered as part of the
NHANES that began in 2002.
Another well-respected automated 24-hour recall is the
Nutrition Data System for Research (NDS-R), developed by
the Nutrition Coordinating Center from the University of
Minnesota (Nutrition Coordinating Center, 2005). The com-
puter-based application allows entry of dietary data in a
standardized fashion and uses a multiple-pass approach for
dietary data collection that prompts for complete food
descriptions, food preparation methods, and diverse amount
descriptions. The Nutrition Data System links to an exten-
sive database that contains values for 136 nutrients, nutrient
ratios, and other food components and includes >18,000
foods, with many ethnic foods and >8000 brand-name prod-
ucts (Nutrition Coordinating Center, 2005).
Food Records
Food records or diaries are detailed descriptions of types
and amounts of foods and beverages consumed over a pre-
scribed period, usually 3–7 days. The record or diary may
be a special form or booklet that contains prompts or sug-
gested categories of foods for each day. In some applica-
369
tions, subjects measure food with scales using specific pro-
cedures (Willett, 1990).
Maintaining a food diary requires meticulous record
keeping; sustaining these activities over even a relatively
short period requires highly motivated literate individuals.
Recording daily intakes often increases subjects’ awareness
of what they are eating, which in turn can lead to immedi-
ate alterations in the diet. Because of this reactive effect of
the participant changing his or her dietary intake by omit-
ting foods to simplify record-keeping, dietary records often
do not represent actual intake (Willett, 1987; Bingham and
Paul, 1998). In dietary intervention studies, a heightened
awareness can be instilled in subjects to enhance the accu-
racy of diet records, and diet records become a teaching
device within the intervention (Willett, 1990).
In general, dietary record keeping is expensive and inap-
propriate for studies focused on past intake. Unlike most
other methods, however, food diaries do not depend heavily
on memory and thus are relatively free from recall bias, com-
pared with other methods. Food records also reduce day-
to-day variation in diet by averaging intake over a number of
days and can control for differential intakes between week-
days and weekends. Furthermore, record-keeping methods
that require foods and beverages to be weighed or measured
dramatically reduce errors associated with estimating portion
size (Willett, 1987). Food records can be invaluable tools
to monitor group compliance in dietary intervention trials;
however, the possibility that compliance may be good during
the period of recall and poor otherwise may promote biases in
reporting. Diet records are one of the several methods for val-
idating FFQs (Willett, 1990).
Food records are being used in large-scale prospective
studies to measure diet at various intervals over time. The
Data Into Nutrients for Epidemiological Research (DINER)
system program is a computerized software system for entry
of 7-day diaries in the EPIC-Norfolk cohort (Welch et al.,
2001). A food list of 9000 food items and values for 24,000
portion sizes have been incorporated into the database. Daily
food intake is recorded in a food diary booklet that is entered
into the DINER system using a series of pull-down menus
that record time of day and meal, food item, amount of food,
method of preparation, and so forth. Food items are then
merged to an extensive database that converts the food items
to nutrients and food groups (Welch et al., 2001).
There are possible drawbacks to recording and inferring
usual intake from 7-day food records (Gersovitz et al., 1978;
Willett, 1990; Flegal, 1999). Seven-day food records require
a high degree of respondent cooperation that may be diffi-
cult to achieve in a large study (Flegal, 1999). Moreover,
food records tend to become less accurate after the first 4
days of record keeping (Gersovitz et al., 1978). Other limi-
tations to food records include inability to fully represent
usual dietary intake and the requirement that the respondent
population be motivated, literate, and cooperative (Willett,
370 Chapter 19/Dietary Assessment
1990). Food records collected over specified time intervals
in a prospective design can, however, be a relatively accu-
rate and unbiased method for assessing dietary intake and
risk of disease (Barrett-Connor, 1991).
Food Frequency Questionnaires
FFQs are designed to assess frequencies with which food
items are consumed during a specified time (Tarasuk and
Brooker, 1997). FFQs generally provide a listing of foods
and include categories to mark, indicating how often a food
item is consumed on a monthly, weekly, or daily basis. The
underlying principle of the food frequency approach is that
average long-term diet, for example, consumption over
months or years, is the conceptually important exposure
rather than intake on a few specific days, such as what is
measured in 24 hours (Willett, 1990). Although recall of diet
>20 years ago is impractical, the food frequency approach
may approximate crude underlying dietary patterns that
have been present over the long term. Two well-known
FFQs, among others, have been used extensively in epi-
demiological studies of diet and cancer (Willett et al., 1985;
Block et al., 1986). In a comparability study of nutrient esti-
mation among subjects who completed both the Willett Food
Frequency Questionnaire (Willett et al., 1985) and the Block
Food Frequency Questionnaire (Block et al., 1986), both
questionnaires were found to be, on the average, inter-
changeable with respect to estimates of nutrients in the
overall diet (McCann et al., 1999).
FFQ data may be affected by the educational level of
research subjects. Completion of FFQs requires cognitive
ability to distinguish how often foods are consumed, remem-
bering which foods are consumed, and recording in such
a way that responses reflect usual intake (Flegal, 1999).
Portion size estimation also requires that respondents
modify and adjust their frequency responses according to,
in some cases, prespecified portion sizes (Willett, 1987).
Being able to specify portion size is another demanding cog-
nitive task. The challenges of completing FFQs may lead to
inaccurate reporting of usual intake.
The dietary assessment method selected may impact the
associations of diet and cancer risk observed. In one
example, diet was assessed with both an FFQ and a detailed
7-day food diary. This study was conducted in the EPIC-
Norfolk cohort among 13,070 women (Bingham et al.,
2003). Total fat measured by the 7-day food diaries was pos-
itively associated with increased breast cancer risk (p for
trend = 0.05), whereas total fat measured by the FFQ was not
associated with breast cancer risk (p for trend = 0.14). An
even stronger difference in measurement methodology was
seen for saturated fat intake, where saturated fat measured by
7-day diaries was strongly associated with breast cancer risk
(p for trend = 0.005) and saturated fat measured by the FFQ
was not (p for trend = 0.23). Models were adjusted for
weight, height, menopausal status, parity, hormone replace-
ment therapy, and nonfat energy (Bingham et al., 2003).
NUTRITIONAL BIOMARKERS
Nutritional biomarkers are biological consequences of
dietary intake or dietary patterns resulting in the presence of
components or metabolic byproducts (Consensus Group for
Biomarkers in Cancer Chemoprevention, 2001; Potischman
and Freudenheim, 2003). Exposure biomarkers may include
endogenous or exogenous agents and their metabolites or
adducts in tissues or body products, whether in physiologi-
cal or pathological amounts. Structural changes in the cell
or organism that reflect exposure are also included (Con-
sensus Group for Biomarkers in Cancer Chemoprevention,
2001). Biomarkers have the capacity to improve risk esti-
mation and define mechanisms of exposure–disease link-
ages. Furthermore, utility of biomarkers in population and
prevention studies is continuous; that is, some markers are
more informative than others, depending on how they are
being used, with a gradation from extremely useful to arti-
factual (Groopman, 2005).
Biomarkers can be sorted into functional use categories
(Consensus Group for Biomarkers in Cancer Chemopre-
vention, 2001), which include the following:
1. Validation of dietary instruments
2. Surrogate indicator of dietary intake
3. Integrated measure of nutritional status for a particular
nutrient
4. Measurement of nutrient metabolism or interaction meta-
bolic byproduct with other factors
Biomarkers and Dietary Assessment
Biomarkers as Validation Tools for
Dietary Assessments
Biomarker measurement can provide complementary
information to help assess performance of different dietary
assessment methods. The objectivity of biomarkers makes
reliance on subjects’ memory or cooperativeness less impor-
tant (Consensus Group for Biomarkers in Cancer Chemo-
prevention, 2001). The use of randomized controlled feeding
trials is one method for validating dietary assessments. Con-
trolled feeding studies in healthy humans have been used to
establish quantitative requirements and confirm functional
levels of nutrients. These studies rely on small sample sizes
with intensive control, including restriction of calories or
feeding of specific nutrients with determination of biologi-
cal availability in specific tissues (Lampe, 2004). Small-
scale intensive feeding studies can be enormously useful
in describing hypothesized mechanisms observed in large
population-based studies.
 Nutritional Biomarkers
An example of validation by feeding trial results is a
study that measured the effect of vegetable intake on plasma
carotenoid concentrations (Martini et al., 1995). High veg-
etable diets consisted of a control diet plus either carrots
and spinach (carotenoid diet), broccoli and cauliflower
(cruciferous diet), or tofu and a textured vegetable protein
product (soy diet). The control diet consisted of commonly
consumed foods and was essentially carotenoid free.
Participants consumed each of the experimental diets for 9
days, with at least a 10-day washout period between diets,
and were instructed to consume no other foods or beverages.
Carotenoid intakes of all diets were calculated using the
updated carotenoid food composition database developed
by Mangels et al. (1993). When compared with the control
diet, mean plasma concentration for α-carotene, β-carotene,
and lutein were 5.2, 3.3, and 2.2 times higher on the
carotenoid diet, respectively; plasma lutein concentrations
were 2.1 times higher on the cruciferous diet. Plasma
concentrations of β-cryptoxanthin and lycopene did not
differ among diets. Carotenoids are widespread in vegeta-
bles and fruits. These data indicate that plasma carotenoid
concentrations may be useful exposure markers for total
vegetable and fruit intake in a free-living population and
might be useful compliance markers in dietary interventions
that emphasize vegetable and fruit intake (Martini et al.,
1995).
Another example of the application of controlled feeding
studies involves a comprehensive investigation that com-
pared results of 12 dietary intervention studies using 7-day
food records with data from controlled feeding studies for
the same individuals (Mertz et al., 1991). Free-living par-
ticipants were trained by dietitians to keep 7-day food
records. Subsequently, participants received diets of con-
ventional foods for 45 days; these diets were adjusted so that
each individual maintained his or her body weight. Partici-
pants reported intakes using 7-day food records; the esti-
mated energy intake from the food records was compared
with the actual intake determined to maintain weight. These
comparisons found that 81% of the total subject population
reported usual energy intakes that were ~700 kcal below the
intake subsequently determined to maintain body weight;
8% reported a higher intake (by ~400 kcal); and 11%
reported and calculated intakes that were within 100 kcal of
each other. The mean difference between recorded and
determined intakes was equally underreported (by ~18%)
for both men and women; age had no effect on reporting
(Mertz et al., 1991).
Use of the doubly labeled water technique, a validated
reference method that permits a precise measure of energy
expenditure in free-living populations, confirmed the afore-
mentioned finding that subjects recording diet records may
underestimate their usual intake substantially (Black et al.,
1993; Hebert et al., 1995; Martin et al., 1996; Sawaya et al.,
1996). A review of studies in randomly recruited men and
371
women that compared dietary energy intake, as assessed
from weighed diet records, with total energy expenditure, as
measured by doubly labeled water, reported that energy
intake was only 82% (men) and 81% (women) of energy
expenditure (Black et al., 1993). A comparison of food
records with data from the doubly labeled water method
found a similar underreporting of ~20% in a subset of
women participating in the Canadian Diet and Breast Cancer
Prevention Trial (Black et al., 1993).
Such analyses suggest that a large proportion of indi-
viduals consistently underestimate caloric intake, even
those who have received training in keeping accurate food
records. The exact reasons for this inaccuracy have not
been determined, although the tendency of an individual
to convey an image in keeping with social norms (e.g.,
low-fat vs high-fat diets) and to avoid criticism in a testing
situation could bias self-reported dietary intake (Hebert
et al., 1995). In any event, caution should be used when
interpreting epidemiological survey data and the results of
other epidemiological studies that use self-reported dietary
assessment instruments to collect food data and estimate
nutrient intake, even those that use multiple-day food
records.
Other validation studies using doubly labeled water
found that both men and women underreported energy and
protein intakes on 24-hour recalls and FFQs (Subar et al.,
2003). In a partnered publication, attenuation of relative risk
estimates by FFQs was lessened by adjusting for energy
intake using nutrient density or nutrient residuals (Kipnis
et al., 2003), suggesting that caution is warranted in inter-
preting results from epidemiological studies that rely on
FFQs to estimate the effects of dietary intake. However,
energy adjustment can correct to some degree the impreci-
sion in estimating the true underlying association between
intake and cancer risk. In a commentary on both studies, it
was noted that the doubly labeled water technique itself is
error prone, suggesting that validation biomarkers carry
their own level of imprecision (Willett, 2003). Most impor-
tantly doubly labeled water sampling needs to be done over
several time points to account for within-subject variation.
FFQs are designed to assess usual intake, whereas 24-hour
recalls and daily food records are designed to assess proxi-
mate and immediate intake. It is assumed that individuals’
food intake varies over time, and that it is important to reli-
ably estimate the effect of foods during the 20–30 year
cancer induction period.
Biomarkers Used in Combination with
Dietary Assessment
Despite ongoing improvements in dietary assessment
methods, errors inherent in these tools persist. The search
for more objective measures of intake is leading researchers
372 Chapter 19/Dietary Assessment
to utilize biomarkers that reflect dietary intake in combina-
tion with those that predict disease outcome or status. Such
biomarkers ideally should (see Pearce et al., 1995; Consen-
sus Group for Biomarkers in Cancer Chemoprevention,
2001)
1. be inexpensive to collect and analyze,
2. be present in small amounts of a biological specimen that
can be obtained using a minimally invasive collection
method,
3. persist for an extended period and reflect all routes of
exposure,
4. be specific and highly predictive of the exposure of
interest,
5. be measurable using a sensitive, specific, and reliable
assay, and
6. be present in low concentrations in unexposed popula-
tions at baseline.
Although it is difficult to meet all of these criteria, there are
several promising biomarkers of intake. For example, tissue
and serum long-chain n-3 and n-6 polyunsaturated fatty
acids have been reported to be reflective of dietary intake of
fish, n-3, and n-6 fatty acids (Lands, 1995; Marckmann
et al., 1995; Andersen et al., 1996; Connor, 1996; Bagga
et al., 1997; Kohlmeier, 1997) and may be indicative of risk
for breast (Kohlmeier, 1997) and prostate (Godley et al.,
1996) cancers. Serum levels of β-carotene have been posi-
tively associated with intake of carotenoid-rich fruits and
vegetables (Mangels et al., 1993; Campbell et al., 1994;
Drewnowski et al., 1997). Several studies also corroborate
the use of vitamin E (α-tocopherol) concentrations in serum
and adipose tissue as measures of external intake (both
dietary and supplemental) of that nutrient (Riemersma et al.,
1991; Rimm et al., 1993).
A convincing body of evidence similarly suggests a direct
relationship between consumption of a variety of soy-based
products, lignans, isoflavones, isoflavonoid phytoestrogens,
and plasma and urinary concentrations (Adlercreutz et al.,
1993; Morton et al., 1994; Hutchins et al., 1995a,b; Kelly
et al., 1995; Gross et al., 1996). Wu et al. (2004) showed a
direct correlation between self-reported soy isoflavone
intake from a FFQ and plasma isoflavone levels drawn from
a subset of both cases and controls in a population-based
study of breast cancer among Asian American women living
in Los Angeles County. These findings suggested that, in this
instance, breast cancer cases and controls were reliably able
to recall their usual soy intake without selective recall biases
(Wu et al., 2004).
Although biomarkers appear to be a promising method
that could replace food frequency methods, it is important
to understand that not all foods have biomarkers of intake.
Moreover, several studies have shown a weak association
between dietary intake and biological markers of intake
(Polsinelli et al., 1998; Crews et al., 2001; El-Sohemy et al.,
2002; IARC Working Group on the Evaluation of Cancer-
Preventive Strategies, 2003). Well-designed studies of
dietary intake and cancer risk ought to include both dietary
recall methods and specific biomarkers of intake.
Biomarkers as Measures of Dietary Exposure
In instances in which specific biomarkers of intake exist
such as serum lycopene level as a marker of tomato product
intake, accuracy of dietary exposure measurement can be
improved by use of biomarkers. Results of epidemiological
studies of fruit, vegetables, and breast cancer risk have been
inconsistent and serve as a good example for how biomark-
ers can potentially increase the accuracy of dietary exposure
measurement.
Fruits and vegetables contain numerous compounds that
have demonstrated anticarcinogenic effects, including
carotenoids (Sato et al., 2002), flavonoids (Le, 2002), and
isothiocyanates (ITCs) (Fowke et al., 2003). Self-reported
dietary intake results from population-based case-control
studies of breast cancer all demonstrate a protective associ-
ation at the highest category of fruit and vegetable con-
sumption (Hirose et al., 2003; Malin et al., 2003; Shannon
et al., 2003), whereas eight prospective cohort studies, when
summarized together, report a null association (Smith-
Warner et al., 2001). Most epidemiological studies rely on
FFQs to measure dietary intake. The increased variability
introduced by self-reported intake has been suggested by
several reviews (WCRF, 1997; Smith-Warner et al., 2001;
Riboli and Norat, 2003) as one of the reasons for inconsis-
tent results of fruits and vegetables and breast cancer risk
observed across studies.
Inverse associations observed for biomarkers of fruit and
vegetable intake have strengthened biological evidence for
fruit and vegetable consumption and reduction of breast
cancer risk. Two nested case-control studies found protec-
tive associations between serum biomarkers of carotenoids
and breast cancer risk (Toniolo et al., 2001; Sato et al.,
2002). A protective association was observed for urinary
ITCs and breast cancer risk in a case-control study of
Shanghai Chinese (Fowke et al., 2003). Dietary intake of
soy (flavonoid family) that was later validated by plasma
isoflavone was found to be protective for breast cancer risk
in a case-control study of Asian Americans conducted in Los
Angeles County (Wu et al., 2002, 2004).
Protective associations between biomarkers of fruit and
vegetable intake and other diseases such as lung cancer have
also been found. Observational studies have consistently
shown that elevated intake of vegetables reduces the risk of
lung cancer (Ziegler et al., 1984, 1986, 1992; Fontham
et al., 1988; Le et al., 1989; Dorgan et al., 1993; Alpha-
Tocopherol, 1994; Mayne et al., 1994; Omenn et al., 1996;
Speizer et al., 1999). A report of fruit and vegetable con-
sumption in two prospective cohorts found the strongest pro-
 References
tective association from cruciferous vegetables, citrus fruits,
and foods high in total carotenoids (Feskanich et al., 2000).
Other large-scale population-based studies have also shown
overall inverse associations between cruciferous vegetable
intake and lung cancer risk (Le et al., 1989; Verhoeven
et al., 1996; Speizer et al., 1999). ITC, a marker for crucif-
erous vegetable consumption and metabolism found in urine
specimens, was inversely related to lung cancer risk in a
population (Shanghai) that consumes high levels of crucif-
erous vegetables. The protective effect was greatest in sub-
jects genetically deficient in glutathione-S-transferase M1
(GSTM1) (London et al., 2000). This observation has been
confirmed in a U.S. Texas population (Spitz et al., 2000) and
in Singapore Chinese (Zhao et al., 2001) using dietary ques-
tionnaire data.
A pooled analysis of eight cohort studies did not find an
association with consumption of broccoli or cabbage and
lung cancer risk (Smith-Warner et al., 2003). On the other
hand, a metaanalysis of cohort studies conducted by the
IARC Working Group on the Evaluation of Cancer Preven-
tive Strategies reported an odds ratio of 0.86 (95% confi-
dence interval [CI] = 0.75–0.98) for the association between
ITCs either measured directly in urine or calculated from
dietary intake reports (IARC Working Group on the Evalu-
ation of Cancer-Preventive Strategies, 2004).
SUMMARY
As research of diet and cancer moves forward, it is clear
that no one method of dietary assessment is ideal. The type
of nutrients under investigation, the study design, the study
hypothesis, and cancer site under investigation will help
determine the optimal assessment instrument and whether
biomarkers of intake should be included. If study design
permits, use of biomarkers and dietary assessment together
appears to be the most accurate and comprehensive method
for measurement of diet in relationship to cancer risk.
Acknowledgment
This research was supported by the National Cancer Institute (1 P01
CA 42710), California Breast Cancer Research Program (9PB-0117), and
the UCLA Center for Human Nutrition.
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