Download Prostate cancer and diet: food for thought?

R EVI E W A R T IC L E
BJUI
Prostate cancer and diet: food
for thought?
BJU INTERNATIONAL
Satoshi Hori, Elizabeth Butler* and John McLoughlin†
Department of Uro-oncology, University of Cambridge, Hutchison/MRC Research Centre,
Cambridge, *Department of Nutrition, Penny Brohn Cancer Care, Chapel Pill Lane, Bristol,
and †Departments of Urology, West Suffolk Hospital, Bury St. Edmunds and Addenbrooke’s
Hospital, Cambridge, UK
Accepted for publication 12 August 2010
What’s known on the subject? and What does the study add?
There has been increasing recognition that diet plays an important role in the pathogenesis
of prostate cancer. Despite this, the largely heterogenous nature of prostate cancer and
nutritional research often means that no definitive conclusions can be drawn for those
seeking answers in this important topic.
In this review article, we summarize the key evidence available in this topic to date. Although
we found mounting evidence on certain nutritional components being important in prostate
cancer prevention and progression, further high quality studies are needed to fully
understand the complex nature of diet and prostate cancer.
• There is now increasing evidence that diet plays a major role in prostate cancer biology and
tumorigenesis.
• In a health conscious society, it is becoming increasingly common for Urologists to be asked
about the impact of diet on prostate cancer.
• In the present review, we explore the current evidence for the role of different dietary
components and its’ effect on prostate cancer prevention and progression.
• A literature search was conducted using PubMed® to identify key studies.
• There was some evidence to suggest that green tea, isoflavones, lycopenes, cruciferous
vegetables and omega 3 polyunsaturated fatty acid intake to be beneficial in the prevention
and/or progression of prostate cancer.
• There was also evidence to suggest that a high total fat, meat (especially well cooked) and
multivitamin intake may be associated with an increased risk of developing prostate cancer.
• To date publications have been highly heterogeneous and variable in quality and design. More
robust, high quality research trials are needed to help us understand the complex relationship
between diet and prostate cancer.
KEYWORDS diet, dietary supplements, prostatic neoplasms, prevention, recurrence
INTRODUCTION Prostate cancer is the commonest male malignancy in the UK with 46 924 new cases reported
in 2008 and is the second leading cause of mortality after lung cancer [1]. There is now
increasing recognition that the Western diet, together with other lifestyle factors such as
physical activity levels, may be a significant risk factor in the development of prostate cancer.
The Western diet tends to be high in animal products and processed, refined foods resulting in
a high intake of saturated fats, processed polyunsaturated fats (such as the trans fats) and
refined carbohydrates. In addition, the Western diet is often low in fresh vegetables, fruit, pulses
and whole grains resulting in a low intake of fibre and phytonutrients. Overall, the Western diet
is often calorie-dense but lacking in certain essential nutrients. By contrast, in Far Eastern
countries, e.g. Japan and China, where the incidence of prostate cancer is lower, the traditional
diet is mainly plant-based and minimally processed or refined. Relatively small amounts of
animal products accompany the vegetables, fruit and other plant foods and overall the diet is
lower in calories than the Western diet but is likely to contain greater amounts of certain
essential nutrients. Particular foods that feature more heavily in a traditional Far Eastern diet
1348
©
BJU INTERNATIONAL
©
2 0 11 T H E A U T H O R S
2 0 11 B J U I N T E R N A T I O N A L | 1 0 7 , 1 3 4 8 – 1 3 6 0 | doi:10.1111/j.1464-410X.2010.09897,10321.x
PROSTATE CANCER AND DIET
that may have an impact on prostate cancer risk include green tea, soy and cruciferous vegetables. Epidemiological studies on migrant
populations from Japan and China to the USA have found that the rate of prostate cancer in these men was higher compared with men in their
native countries. By the second generation, their incidence rate was fast approaching those of the average American [2,3]. These studies suggest
a strong environmental factor in the development of prostate cancer.
With an ever increasing source of information
available from the internet and mass media,
our patients have become better informed
about the health benefits associated with
dietary and lifestyle modifications. Indeed the
sheer number of studies available on this
subject means that there are often no
clear-cut answers for patients and their
family seeking answers regarding the effect of
diet and prostate cancer. Thus, it is of
importance that Urologists are aware of the
current evidence to appropriately counsel
patients seeking advice on this frequently
asked topic.
In the present article, we focus on reviewing
the current evidence for different dietary
components and its’ impact on prostate
cancer prevention and progression.
METHODS
A literature search was performed on
PubMed® until May 2010 to identify key
studies investigating the association between
dietary components and prostate cancer. The
search terms included: diet, dietary, nutrition,
supplement, prostate, prostatic neoplasm,
prevention, progression, green tea,
polyphenol, soy, phytooestrogen, tomato,
lycopene, vegetable, vitamin, selenium,
calcium, dairy, fish, omega-3, omega-6, fatty
acid, fat, meat, heterocyclic amine and
carbohydrate. The search was limited to
publications in the English language. To
limit the size of this review, results from
randomised controlled trials (RCTs) were
©
favoured over observational studies due to
the higher quality of methodological design.
Additionally, results from systematic reviews
or meta-analysis of RCTs/observational
studies were given preference to quoting
individual studies where appropriate. Lifestyle
interventions and prostate cancer was not
included in our search as it is beyond the
scope of this article.
RESULTS
Green tea
Green tea plays a major role in the oriental
diet and has been consumed in the Far East
for several thousand years. Green tea, derived
from the plant Camellia sinensis, contains
polyphenolic compounds, which have
previously been suggested to decrease the risk
and slow the progression of prostate cancer in
vitro and in vivo [4]. The most abundant and
the best studied polyphenolic compound is
(−)-epigallocatechin-3-gallate (EGCG), an
antioxidant that is 25–100 times more potent
than Vitamin C and E [5]. Suggested
mechanisms of the anti-tumourigenic action
of green tea include apoptosis and cell cycle
arrest via alterations in the mitogen-activated
protein kinase, phosphatidylinositol-3-kinase
(PI3K)/Akt and protein kinase C pathways,
inhibition of inflammatory pathways [nuclear
factor κB and cyclooxygenase-2 (COX-2)] and
modulation of the insulin-like growth factor
(IGF) and androgen receptor (AR) axes [6].
To date, clinical studies have yielded some
promising results. A large prospective cohort
study of 49 920 men aged 40–69 years and
their green tea consumption habits was
conducted by the Japan Public Health Centre
between 1990 and 2004 [7]. During this time,
there were 404 cases of newly diagnosed
prostate cancer of which 114 cases were
advanced, 271 were localized and 19 were of
an undetermined stage. The results indicate
that there may be a dose-dependent decrease
in the risk of advanced prostate cancer in men
who consume > 5 cups of green tea per day
[relative risk (RR) 0.52]. Bettuzzi et al. [8] in a
small proof-of-principle trial, set out to assess
the efficacy of daily green tea supplement in
patients at a higher risk of developing
prostate cancer. In all, 60 patients with highgrade prostatic intraepithelial neoplasia
(HGPIN) were randomized to receive daily
green tea supplementation vs placebo. The
authors reported that there was a highly
significant reduction in the incidence of
prostate cancer in the group given daily green
tea supplements compared with the group
who took placebo alone [nine of 30 (30%) vs
one of 30 (3%)]. In addition, the PSA values in
the green tea supplement group remained
constantly lower than those given placebo
alone, although this was not statistically
significant.
A few studies have also investigated the role
of green tea in patients with confirmed
prostate cancer. In a multicentre, single-arm,
open-label Phase II trial, the effect of green
tea powder supplementation was evaluated in
42 patients with metastatic castrationresistant prostate cancer (CRPC) [9]. Of the 42
patients evaluated in this study, only one
2 0 11 T H E A U T H O R S
BJU INTERNATIONAL
©
2 0 11 B J U I N T E R N A T I O N A L
1349
H O R I ET AL.
to the same conclusion [odds ratio (OR) 0.69,
95% CI
0.57–0.84].
had a > 50% reduction in PSA level after
supplementation with green tea powder. For
the rest of the cohort, there was a median
increase of 43% in PSA level from baseline
to the end of the first month after
commencement of supplementation. Another
similar study by Choan et al. [10] evaluated
the role of green tea supplementation at a
dose of 250 mg given orally twice daily in
patients with CRPC. This study also yielded
disappointing results, with no patients
achieving a significant reduction in their PSA
levels. In conclusion, although green tea
appears to have some benefit in the
prevention of prostate cancer, there is no
data currently supporting the increased
consumption of green tea amongst men with
confirmed prostate cancer.
Soy phytooestrogens
Interest in soy phytooestrogens stem mainly
from epidemiological findings that a lower
incidence of prostate cancer occurs in Far
Eastern countries where the consumption
of soy products are typically high.
Phytooestrogens are a group of biologically
active plant compounds with a chemical
structure similar to oestradiol [11] of which,
isoflavones are the most important. Food
sources rich in isoflavones include soy bean,
tofu, kidney beans, chick peas, lentils and
peanuts. Isoflavones have been shown to alter
the expression of numerous genes associated
with prostate cancer [12] and is postulated to
work mainly through its’ oestrogenic effect,
binding to oestrogen receptors and thereby
suppressing cellular proliferation and
promoting differentiation in vitro and in vivo
[13].
Several clinical studies have investigated the
role of isoflavones in prostate cancer
prevention. A metaanalysis by Yan and
Spitznagel [14]
‘Several clinical studies have investigated the
based on eight
role of isoflavones in prostate cancer prevention’ observational
studies, examined
the relationship between soy isoflavone
intake and the risk of developing prostate
cancer. That study concluded that when
individual study results were pooled, the
overall risk estimate of developing prostate
cancer with high soy consumption was 0.70
(95% CI 0.59–0.83, P < 0.001) indicating an
inverse association between soy consumption
and risk of prostate cancer. A more recent
meta-analysis by Hwang et al. [15] also came
1350
Several small clinical trials have evaluated the
effect of consuming a diet rich in soy
isoflavones in patients with confirmed
prostate cancer. Bylund et al. [16] performed a
small RCT on 10 men with confirmed prostate
cancer who were on active surveillance. Men
in that study were randomized to receive
a daily supplement of rye bran bread
(phytooestrogen rich food) or to receive
wheat bread (control). Although the authors
did not report any statistically significant
change in PSA levels in the group treated
with phytooestrogen, apoptotic markers
as measured by the TUNEL (terminal
deoxynucleotidyl transferase-mediated dUTP
nick end-labelling) method, indicated a
significant increase in the group given high
phytooestrogen supplementation (P < 0.005).
A slightly larger RCT by Kumar et al. [17] of
59 men with prostate cancer on active
surveillance yielded similar results, failing
to show any beneficial effect of a high
phytooestrogen diet and PSA reduction. On
the other hand, Dalais et al. [18] performed a
double-blind RCT of high phytooestrogen diet
(soy) vs low phytooestrogen diet (wheat) in
men awaiting radical prostatectomy (RP) and
reported a statistically significant decrease in
PSA amongst the group who received a high
phytooestrogen diet compared with the
control group (decrease in PSA level of
12.7% vs an increase of 40%, respectively,
P = 0.02). In summary, current evidence
indicates a possible protective effect of
high phytooestrogen diet in prostate
cancer prevention but only limited evidence
amongst patients with confirmed prostate
cancer.
Tomatoes and lycopenes
Lycopene is a bright red carotenoid
pigment abundantly found in tomatoes,
watermelon and grapefruit. In vitro, it has
been shown to exert an antiproliferative
effect by inhibiting the cell cycle at the
G0/G1 phase [19]. It has also been shown
to increase the number of IGF-1 binding
proteins [20] resulting in a net decrease in
serum IGF-1, which has previously been
associated with an increased susceptibility to
prostate cancer [21]. As such, it has been
postulated that lycopene may be beneficial in
the prevention and progression of prostate
cancer.
©
BJU INTERNATIONAL
©
2 0 11 T H E A U T H O R S
2 0 11 B J U I N T E R N A T I O N A L
PROSTATE CANCER AND DIET
A meta-analysis of 21 observational studies
[22] evaluating the role of lycopene in
prostate cancer prevention reported that
compared with infrequent consumers of
tomato products, those eating a lot of raw
tomato and cooked tomato products had a RR
of developing prostate cancer of 0.89 (95% CI
0.80–1.00) and 0.81 (95% CI 0.71–0.92),
respectively, suggesting that a high intake of
tomato products has a modest role in the
prevention of prostate cancer. Similarly, there
is some evidence to suggest that lycopene
supplementation may also be of benefit in
men with confirmed prostate cancer. A recent
systematic review of eight interventional
studies by Haseen et al. [23] has shown an
inverse association between lycopene intake
and serum PSA levels in six of the studies [24–
29]. It is also worth noting that in one of the
studies, a RCT of lycopene and orchidectomy
vs lycopene alone in men with metastatic
prostate cancer [30], the results have been
particularly encouraging with radiological
evidence of disease retardation on serial
bone scans in the group given lycopene
supplementation. However, more recently a
small prospective open phase II study of daily
lycopene supplementation (15 mg) in men
with progressive CRPC did not result in any
clinically significant benefit in this group of
patients although five of 17 patients had a
plateau-like stabilization in their PSA levels
[31]. In addition, the USA Food and Drug
Administration (FDA) carried out an evidencebased review of the literature in response to
the growing number of claims that lycopene
is beneficial in reducing certain types of
cancer including prostate cancer [32]. In all,
13 observational studies evaluating the
association between increased tomato or
lycopene supplementation and prostate
cancer were evaluated. The FDA concluded
that at present, there was only very
limited evidence to support an association
between tomato/lycopene consumption
and reduced risk of prostate cancer. In
summary, although there is promising
data in the current literature, further
large scale RCTs are required to investigate
a more concrete beneficial association
between lycopene/tomato consumption
and prostate cancer.
active ingredient in cruciferous vegetable,
isothiocyanates (a metabolic derivative of
glucosinolates) has been shown to have
potent anticancer properties [33–36]. A recent
study has shown phenethyl isothiocyanates
to repress AR transcription and expression,
mediating growth arrest in both androgendependent and androgen-independent
prostate cancer cells [37].
Several epidemiological studies have
previously reported a reduced incidence of
prostate cancer amongst men who have a
high consumption of cruciferous vegetables
[38–40] but studies that are more recent have
failed to show this effect [41–44]. Currently
therefore, there is only limited evidence that
cruciferous vegetable may play a protective
role in the development and progression of
prostate cancer.
Vitamins
Cruciferous vegetables
Vitamins are a group of structurally and
functionally unrelated organic compounds
that are essential for the normal functioning
of the body and are present in various
different food sources. Foods rich in vitamin A
(retinol and carotenes) include cheese, eggs,
liver, oily fish, vegetables and fruit. The B
vitamins are found in a wide variety of foods.
For example, B6 (pyridoxine) is found in
pork, chicken, turkey and cod whilst B12
(cobalamin) is found in meat, salmon, cod,
milk and cheese. Vitamin C (ascorbic acid) is
present in various fruit and vegetables
including pepper, broccoli, brussels sprouts,
oranges and kiwi, whilst most vitamin D is
synthesized from our skin in response to sun
light but is also found in eggs, liver, butter and
oily fish. Vitamin E is found mainly in plant
oils such as soya, corn or olive oil whilst
vitamin K is abundant in leafy vegetables such
as spinach and broccoli. There is now
increasing recognition that vitamins are
important not only for the normal
functioning of our bodies, but that they also
appear to possess several anti-tumorigenic
properties in vitro. Possible mechanisms for
this includes the activation of pro-apoptotic
and cell cycle arrest transcription factors,
modulation of epigenetic events, interaction
with AR and also through anti-oxidative
mechanisms [45].
Cruciferous vegetables are part of the
Brassicaceae family which includes
horseradish, broccoli, cabbage, brussels
sprout, cauliflower, bok choy and wasabi. The
Virtually all clinical studies to date have
investigated the association of vitamin usage
and prevention of prostate cancer. Vitamin A
is found principally in two main food forms as
©
retinol and carotenes. The Carotene and
Retinol Efficacy Trial (CARET) was a doubleblind RCT investigating the effects of carotene
and retinol supplementation on preventing
lung cancer amongst high-risk patients [46].
As a secondary outcome, they were also
interested in evaluating the potential
association with prostate cancer [47]. Men
in the interventional arm who also used
additional dietary supplements had an
increased RR towards developing an
aggressive prostate cancer (RR 1.52, 95% CI
1.03–2.24; P < 0.05) compared with those
who did not, although this association
disappeared on cessation of the trial. The
authors concluded therefore that the
excessive use of high-dose vitamins especially
when taken in combination may increase the
risk of developing aggressive prostate cancer.
This association has also been reported in the
National Institutes of Health (NIH)-AARP
Diet and Health study where excessive
multivitamin intake was associated with an
increased risk of patients developing
advanced or fatal prostate cancer (RR 1.32,
95% CI 1.04–1.67 and RR 1.98, 95% CI
1.07–3.66, respectively) [48].
Several RCTs have evaluated the role of
vitamin E either alone or combined with other
vitamins. The α-tocopherol, β-carotene
Cancer Prevention Study (ATBC) was a large
RCT investigating the effect of vitamin A (βcarotene) and/or vitamin E (α-tocopherol)
supplementation in the prevention of lung
and other cancers [49]. After a median followup of 6 years, there was a 34% reduction in
the incidence of prostate cancer amongst
participants randomized to vitamin E (αtocopherol) supplementation whilst there was
a modest but statistically insignificant
increase in prostate cancer risk amongst
those patients given vitamin A (β-carotene)
supplementation [50]. The authors concluded
that vitamin E (α-tocopherol) appears to have
a favourable effect in reducing the risk of
prostate cancer but that these findings
would need to be substantiated in further
studies.
Unfortunately, subsequent studies on vitamin
E have failed to reproduce the initial benefit
reported in the ATBC study. Two large
observational studies, the Cancer Prevention
Study II Nutrition Cohort [51] and the NIHAARP Diet and Health Study [52] both failed
to show any beneficial association between
vitamin E supplementation and prostate
cancer risk. A recent RCT, the Physicians’
2 0 11 T H E A U T H O R S
BJU INTERNATIONAL
©
2 0 11 B J U I N T E R N A T I O N A L
1351
H O R I ET AL.
Health Study investigated the effect of longterm vitamin C and/or E supplementation on
prostate cancer and found that neither
vitamins decreased the risk of prostate cancer
[53]. The interim results of the much
anticipated Selenium and Vitamin E Cancer
Prevention Trial (SELECT) have also recently
become available [54]. This large, doubleblind, placebo-controlled RCT of 35 533 men
randomized to receive selenium, selenium and
vitamin E, vitamin E alone, and placebo was
terminated early as the interim analysis failed
to show any benefit with either components
in reducing the risk of prostate cancer. In
addition, there was also a trend in the vitamin
E group in developing prostate cancer
although this association was statistically not
significant (P = 0.09).
In summary, results from several large
observational and RCTs to date have failed to
show any beneficial role of vitamin
supplements in reducing the risk of prostate
cancer. On the contrary, some studies even
suggest that multivitamin supplements may
be associated with an increased risk of
prostate cancer.
Selenium
Selenium is a trace mineral that serves as an
antioxidant, which helps prevent cellular
damage from free radicals. It is found in large
quantities in Brazil nuts, fish such as tuna and
swordfish as well as in molluscs and oysters.
In vitro studies have shown selenium to
inhibit angiogenesis, inhibit cellular
proliferation and induce apoptosis [55]. Earlier
enthusiasm for selenium supplementation
came from the result of a large scale RCT in
the 1990s, the Nutritional Prevention of
Cancer trial [56], which was initially set
up to investigate the effect of selenium
supplementation for
prevention of skin
cancer recurrence in
‘Dairy products such as milk, butter, cheese and men with a past
history of cutaneous
yoghurt have all previously been postulated to
malignancy.
increase the risk of developing prostate cancer’
Although that study
did not show any
protective effect of selenium againstthe
development of skin cancer, it incidentally
found that supplementation with 200 μg
selenium was associated with a lower
incidence of lung, colorectal and prostate
cancer. This beneficial effect of selenium
against prostate cancer was also reflected in a
meta-analysis of 20 epidemiological studies
1352
that showed a significant increase in the
incidence of prostate cancer amongst men
with low levels of serum selenium [57].
Such findings may be of particular relevance
in populations with low levels of selenium in
the topsoil such as the UK where ice age
glaciers are thought to have washed out a
large proportion of the selenium from the
topsoil. As most of wheat in the UK is now
grown on home soil, this may magnify the
dietary deficiency of selenium in the UK
population.
The studies above initially raised the prospect
of using selenium supplementation for
chemoprevention of prostate cancer.
However, the interim results of the SELECT
trial [54] were disappointing, showing no
benefit of selenium alone or when combined
with vitamin E for prevention of prostate
cancer, which led to the early closure of this
trial. Recently, the results of another large
multicentre phase III RCT using selenium vs
placebo in men with HGPIN has proved
equally disappointing with no benefit seen in
the intervention group receiving selenium
supplementation [58]. The role of selenium
supplementation in men with an already
established diagnosis of prostate cancer
was recently studied by Chan et al. [59].
The authors concluded that selenium
supplementation in certain patients
may result in a more aggressive
prostate cancer phenotype especially
when patients have an altered genotype
for the manganese superoxide dismutase
(SOD2) enzyme. These results taken together
now challenge the previous notion of a
protective role of selenium supplementation
with some studies even suggesting the
converse.
Dairy products and calcium
Dairy products such as milk, butter,
cheese and yoghurt have all previously
been postulated to increase the risk of
developing prostate cancer. This increased
risk may in part be attributable to the high
amount of saturated fat present in dairy
products but the more likely mechanism
underpinning this association is the relative
suppression of 1,25 dihydroxyvitamin D3 (an
active form of vitamin D metabolite) in
response to the increased levels of plasma
calcium associated with a high dairy diet
[60]. In vitro studies have shown 1,25
dihydroxyvitamin D3 to halt cellular
proliferation and promote apoptosis in
©
BJU INTERNATIONAL
©
2 0 11 T H E A U T H O R S
2 0 11 B J U I N T E R N A T I O N A L
PROSTATE CANCER AND DIET
several different human cell lines including
prostate cancer cell lines [61–66]. In
addition, an increased dairy product
intake may also influence the levels of
circulating IGF-1, which has been shown
to increase the risk of developing prostate
cancer [67–69].
Clinical studies examining the relationship
between dairy product/milk and prostate
cancer have revealed conflicting results. A
meta-analysis performed by Gao et al. [70] of
16 prospective studies showed a positive,
albeit small association between high dairy
product, calcium intake and prostate cancer
(RR 1.11, 95% CI 1.00–1.22; P = 0.047 and
RR 1.39, 95% CI 1.09–1.77; P = 0.018,
respectively). Similarly, a more recent
meta-analysis of 18 cohort studies [71]
also concluded that the consumption of
milk and dairy products was associated
with a small increased risk of developing
prostate cancer (RR 1.13, 95% CI 1.02–1.24).
However, on the contrary a large recent
meta-analysis of 45 observational studies
showed no evidence of an increased risk of
developing prostate cancer with increased
dairy product (RR 1.06, 95% CI 0.92–1.22) or
milk consumption (RR 1.06, 95% CI 0.91–1.23)
[72].
In patients with confirmed prostate cancer,
the current literature specifically examining
the relationship between dairy product
consumption and prostate cancer progression
is sparse. One study evaluated this effect
indirectly by randomizing patients with
localized prostate cancer to either attend
a series of intensive dietary and cooking
classes or not [73]. The randomized group
attending these classes was noted to have
a significant reduction in the consumption
of saturated fat, animal protein and dairy
products. Although men randomized to
the interventional arm of the study had
a PSA level rise similar to those of the
control group, there was a substantially
longer PSA-doubling time in this group
at the 3-month follow-up visit. It remains
to be seen therefore in future studies
whether alterations in dairy or calcium
intake do actually alter the natural history
of prostate cancer progression. In summary,
there is some conflicting evidence to suggest
that a high dairy consumption is associated
with an increased risk of prostate cancer.
Little is currently known about the effect
of dairy consumption and prostate cancer
progression.
©
Fish and omega 3 (n-3) and 6 (n-6)
polyunsaturated fatty acids (PUFA)
Polyunsaturated fats such as omega 3 and 6
are essential fatty acids derived entirely from
the diet, as the body is unable to synthesize
these de novo. Oily fish such as tuna, sardine,
salmon and trout are an excellent source of
omega 3 PUFA whilst food such as eggs,
avocado, nuts and most vegetable oils are rich
in omega-6 PUFA.
Omega-3 PUFA has previously been shown to
possess several anticancer properties both in
vitro and in vivo. For example, studies using
prostate cancer cell lines have shown the
inhibitory effect of omega 3 PUFA on both
androgen sensitive (LNCaP) and androgen
insensitive (PC3) cell lines [74,75]. Omega 3
has also been shown to exert an inhibitory
effect on androgen-independent DU145
prostate cancer cells implanted s.c. in nude
mice [76,77].
Omega 6 PUFA on the other hand has an
adverse effect if taken in excess and has been
implicated in the development of several
cancers including prostate in vitro and in vivo
[78,79]. Omega 6 PUFA (namely arachidonic
acid) is converted by COX-2 enzyme into
prostaglandin E2, a pro-inflammatory
cytokine implicated in the development of
several cancers [80]. Omega 3 PUFA competes
against omega 6 as a substrate for COX-2
enzyme resulting in the production of
prostaglandin E3 [81], which does not possess
mitogenic properties [82].
Several clinical studies have been conducted
to evaluate the role of omega 3 PUFA and
prostate cancer. A few large observational
studies have suggested a beneficial
association between high fish or omega 3
PUFA consumption and reduced risk of
developing prostate cancer [83–85]. For
example, Terry et al. [83] investigated the
effect of dietary fish intake amongst 6272
Swedish men who were followed-up for 30
years. That study reported that men who ate
no fish had a two–three-fold increase in the
risk of developing prostate cancer compared
with those who consumed large amounts of
fish in their diet (RR 2.3, 95% CI 1.2–4.5;
P = 0.05). Although most studies suggest
omega 3 PUFA to be protective against
prostate cancer, there are also studies to the
contrary. A review of eight prospective cohort
studies and nine case-control studies failed to
show any convincing beneficial effect of high
fish and omega 3 PUFA intake and prostate
cancer [86]. A more recent systematic review
also concluded that the current literature
does not provide sufficient evidence to
suggest a beneficial association between
omega 3 PUFA consumption and cancer
prevention. One large prospective cohort
study even suggested an increased risk of
developing advanced prostate cancer with the
consumption of a certain type of omega 3
PUFA known as α-linolenic acid from both
non-animal and animal sources (RR 2.02, 95%
CI 1.35–3.03 and RR 1.53, 95% CI 0.88–2.66,
respectively) [85].
A few clinical studies have examined the
effect of omega 3 PUFA in patients with
prostate cancer. Demark-Wahnefried et al.
[87] performed a case-control pilot study to
examine whether a diet high in omega 3 PUFA
influences biomarkers involved in prostate
carcinogenesis. In all, 25 patients with
localized prostate cancer who were awaiting
RP were recruited and given omega 3
supplementation (flaxseed) together with a
low fat diet and were matched to a historical
control. Although the study did not show any
statistically significant decrease in PSA levels,
other markers of prostate cancer activity such
as total testosterone and free androgen index
decreased significantly in their respective
values. More recently, the same group
performed a RCT and reported that in those
men who received flaxseed supplementation
before RP, there was a statistically significant
decrease in tumour proliferation rates
compared with controls (P < 0.002) [88].
Presently therefore, there is evidence to
suggest that fish and omega 3 plays an
important role in reducing the risk of prostate
cancer development and may also be
beneficial amongst men with prostate
cancer.
Fats
High total fat and meat consumption in
the Western diet have been linked to an
increased risk of prostate cancer in several
epidemiological studies [89]. Fats are a wide
group of compounds that are chemically
comprised of triesters of glycerol and fatty
acids and are obtained from a wide variety of
animal and plant sources. Examples of edible
animal fat include lard, fish oil and butter that
are obtained from animal skin, meat or milk.
Soya bean, peanut, sunflower, sesame, olive
and vegetable oils are some examples of
edible plant fats. Total fats, especially from
2 0 11 T H E A U T H O R S
BJU INTERNATIONAL
©
2 0 11 B J U I N T E R N A T I O N A L
1353
H O R I ET AL.
animal sources, have been suggested to
increase the risk of developing prostate
cancer. The exact mechanism by which dietary
fat induces prostate carcinogenesis or
prostatic growth is currently unclear.
However, it is likely that the hormone IGF-1
plays an important role in dietary fat-induced
prostate cancer. Barnard et al. [90] have
previously shown in a feeding experiment
that the serum obtained from patients given a
low fat diet had much lower plasma
circulating levels of IGF-1 compared with
controls. Interestingly they also found that
LNCaP prostate cancer cells grown on serum
of these patients grew at a much slower
rate compared with those given a normal
fat diet, suggesting that IGF-1 plays a major
role in determining prostate cancer cell
behaviour.
A meta-analysis of 29 studies investigating
the effect of dietary fat intake and prostate
cancer risk was undertaken by Dennis et al.
[91]. The authors concluded that although
there appears to be a small but significant
increase in the risk of developing prostate
cancer with dietary fat consumption
of > 45 g/day (RR 1.2), the analysis of these
studies were problematic due to the large
heterogeneity between studies. More recently,
the World Cancer
Research Fund
(WCRF) and the
‘At present, there is little evidence to suggest
American Institute
that a diet high in fat is associated with
for Cancer Research
(AICR) also
an increased risk of prostate cancer’
published a report
evaluating several
dietary factors that may be associated with an
increased risk of prostate cancer [92]. The
authors reported similar difficulties in
extrapolating and pooling results from
previous studies for a robust conclusion to be
reached mainly due to the large variability in
study quality and design. However, since the
publication of this report in 2007, there have
been three large prospective trials that have
not shown any correlation between dietary
fat intake and the risk of developing prostate
cancer [93–95].
Several clinical studies have also examined
the effect of reducing total dietary fat intake
in the context of maintaining a general
healthy diet and lifestyle. A pilot study
evaluating the effect of dietary fat restriction
combined with flaxseed supplementation in a
group of newly diagnosed patients with
prostate cancer awaiting RP, observed that
1354
those who were on a low fat and flaxseed diet
had a significantly lower total plasma
testosterone levels compared with controls
[87]. A RCT by Ornish et al. [96] investigated
the effects of intensive dietary and lifestyle
changes on PSA level trends in patients with
confirmed prostate cancer. In the active
intervention arm, patients were given a diet
low in fat and simple carbohydrates and high
in fruit, vegetables, whole grains, legumes and
soy products. Additionally, patients in the
intervention arm underwent intensive
lifestyle modifications, which included stress
management techniques, daily meditation
and progressive relaxations. Interestingly,
patients randomized to the intervention arm
had a 4% decrease in PSA levels compared
with a 6% increase in the control arm. The
authors also found that LNCaP prostate
cancer cells that were grown on serum from
patients in the intervention group were
inhibited almost eight times more than by
serum obtained from the control group (70%
vs 9%, P < 0.001). The results of that study
appear to suggest that simple dietary changes
together with a general healthy lifestyle may
positively influence the progression of
prostate cancer.
At present, there is little evidence to suggest
that a diet high in fat is associated with an
increased risk of prostate cancer. Reduction of
dietary fat intake combined with a general
healthy diet and lifestyle may be beneficial in
slowing down the rate of progression of
prostate cancer in certain patients.
Carbohydrates
Carbohydrates (or saccharides) are a major
source of energy accounting for 45–70% of
total energy intake and expenditure in
humans [97]. Food sources rich in simple
carbohydrates include table sugar, corn syrup,
fruit, white bread, white pasta, fizzy drinks
and cakes, whilst complex carbohydrates can
be found in potato and whole grains such as
brown rice and whole-wheat products.
Carbohydrates, particularly those with a high
glycaemic load consumed in excessive
amounts result in increased fat stores due to
influences on blood glucose and excess
calories. This results in a state of relative
hyperinsulinaemia and obesity, which has
been postulated to increase the risk of
developing prostate cancer through higher
bioavailability of circulating oestrogen and
IGF-1 [69]. Indeed a recent case-control study
evaluating the dietary habits of 1294 Italian
©
BJU INTERNATIONAL
©
2 0 11 T H E A U T H O R S
2 0 11 B J U I N T E R N A T I O N A L
PROSTATE CANCER AND DIET
men found that starch consumption is
directly associated with an increased risk of
prostate cancer (OR 1.4, 95% CI 1.1–1.8) [98].
The effect of carbohydrate on prostate cancer
has been investigated in several in vivo
studies [99–101]. Mice injected s.c. with
androgen-sensitive LNCaP prostate cancer
cells that were fed on a high carbohydrate
(40% carbohydrate, 45% fat, 45% protein)
diet were heavier (P = 0.003), had higher
levels of serum insulin and IGF-1 (P = 0.039)
and had a 45% relative increase in prostate
cancer tumour volume compared with mice
given a low carbohydrate diet (10%
carbohydrate, 45% fat, 45% protein) [99].
Even in experiments where body weight was
maintained, mice on low carbohydrate (12%
fat, 71% carbohydrate, 17% protein) or a no
carbohydrate (83% fat, 0% carbohydrate,
17% protein) diet had a significantly
prolonged survival compared with mice
on a typical Western diet (40% fat, 43%
carbohydrate, 17% protein) with a HR of 0.49
(95% CI 0.29–0.79, P = 0.004) and 0.59 (95%
CI 0.37–0.93, P = 0.02), respectively [101].
Interestingly, the phospho-Akt:total-Akt ratio
in prostate cancer cells from mice in both
these studies had increased with a higher
carbohydrate consumption, presumably as a
result of higher circulating serum insulin and
IGF-1 levels [99,101]. The results of these
studies therefore seem to suggest that
carbohydrate (and not calorie restriction) has
a direct influence on prostate cancer biology
and growth in vivo.
In humans, studies evaluating the direct
impact of carbohydrate intake and prostate
cancer are currently lacking. In a small
feasibility study, Lin et al. [102] examined
whether a low fat, low carbohydrate diet
(classified according to glycaemic load) can
alter the gene expression in prostatic tissues
of men awaiting radical RP compared with
men who were given a control (Western) diet.
In that study, men who were randomised to
receive a low-fat low-carbohydrate diet had a
significant alteration in several genes involved
in cell migration and intracellular signal
transduction. The study therefore provides
exciting data suggesting that carbohydrate
consumption directly alters gene expression
in prostatic tissue but is limited by the few
cases (eight patients) and lack of multiple
intervention arms.
In summary, although several studies suggest
a possible adverse effect of increased
©
carbohydrate consumption and prostate
cancer, most evidence to date stems from
small preclinical studies. Further studies and
RCTs are urgently required to investigate the
potential role of carbohydrate consumption
and prostate cancer in humans.
Meat
There is now increasing evidence that
heterocyclic amines (HCAs) found in
cooked meat are crucial carcinogens that
have been implicated in the pathogenesis
of several human cancers [103]. HCAs are a
group of compounds formed during high
temperature cooking from the reaction of
creatine, amino acids and sugars [104].
2-amino-1-methyl-6-phenylimidazo[4,5b]pyridine (PhIP) is a type of HCA that has
been particularly shown to induce prostate
cancer in vivo and is postulated to act on DNA
causing subsequent instability and
mutagenesis [105].
Several clinical studies have evaluated the
relation between increased meat intake
and the risk of prostate cancer. Kolonel
et al. [89] found in a large epidemiological
review of 22 observational studies that
several of the evaluated studies had a
statistically significant positive correlation
between increased meat consumption and
the risk of developing prostate cancer. More
recently, Zheng and Lee [103] expanded this
observation further by reviewing the
literature for the association between high
HCAs/well done meat and prostate cancer. Of
the four published studies reviewed in this
article, three [106–108] have consistently
shown a positive correlation between very
well done meat and risk of developing
prostate cancer.
In patients with confirmed prostate cancer, it
is currently not known whether a high meat
intake affects the progression of the disease.
However, a recent prospective study of 1294
men with prostate cancer did not identify
any association between increased meat
consumption and prostate cancer recurrence
or progression [109]. Taken together, the
current evidence seems to suggest that a high
meat diet, particularly if very well cooked, may
be associated with an increased risk of
developing prostate cancer. The association
between high meat consumption and
prostate cancer progression is currently
unclear.
CONCLUSION
In an increasingly health conscious society, it
is commonplace for Urologists to be asked
about what constitutes an ‘ideal’ diet for the
prostate. In addition, a growing number
of patients consume vitamins, dietary
supplements and other complementary
medicine remedies in the belief that they are
all ‘natural, safe and good for you’ [110]. We
found evidence in the present review that
certain vitamins for example, when taken
in combination can result in an increased
risk of aggressive prostate cancer [47,48].
Additionally, recent data from the American
Association of Poison Control Centre has
shown a stark increase in the number of
adverse events and deaths as a result of
vitamin, herbal or dietary supplement
consumption from 14 006 to 125 595
adverse events and 5–27 deaths between
1983 and 2005, respectively [111]. Patients
should therefore be advised of the
potential benefits and risks of taking
supplements and should be warned that
not all supplements or alternative remedies
are of benefit.
At present, there is no single dietary factor
that has been shown to conclusively reduce
the risk of developing or delaying the
progression of prostate cancer. However, it is
increasingly evident that diet plays a major
role in the pathogenesis of prostate cancer
and that general dietary modification may be
of benefit to patients. Also, it is important to
note that the current evidence is limited
largely due to the heterogeneous nature of
the studies, which vary greatly in design and
quality. In addition, much of the current
nutritional studies assume a traditional linear
cause-effect relationship where a single
dietary component is investigated for a
particular effect. This reductionism approach
may not be optimal in the study of complex
systems such as diet and health [112]. It is
therefore of paramount importance that a
concerted effort is made amongst the
Urological and Nutritional communities to
improve the design of studies and produce
more robust, high quality research trials that
will help us improve our understanding of the
complexities that exist between diet and
prostate cancer.
Given these limitations however, and based
on the analysis of the current literature, we
feel that the ‘ideal’ prostate diet would be
comprised of a diet low in saturated fat,
2 0 11 T H E A U T H O R S
BJU INTERNATIONAL
©
2 0 11 B J U I N T E R N A T I O N A L
1355
H O R I ET AL.
refined carbohydrates, meat and dairy
products with high vegetable, tomatoes (both
cooked and uncooked), soy and green tea
consumption. In addition, an increasing body
of evidence suggests that lifestyle (mainly
obesity) is a major risk factor for several
cancers including prostate cancer [113].
Patients should therefore also be encouraged
to maintain a healthy weight and lifestyle
through healthy eating and regular exercise.
When educating and discussing the complex
nature of diet and prostate cancer with
patients, it is useful to use an analogy that has
been suggested by Moyad and Lowe [114],
who draw attention to the fact that a
sedentary Western lifestyle is a major risk
factor for both cardiovascular as well as
prostatic diseases. ‘Heart healthy equals
prostate healthy’ is probably the most
effective way of summarizing the importance
of healthy dietary intake and lifestyle in
patients seeking advice on this important
topic.
4
5
6
7
8
ACKNOWLEDGEMENTS
Satoshi Hori gratefully acknowledges
the financial support given by the Royal
College of Surgeons of England Surgical
Research Fellowship and the Addenbrooke’s
Charitable Trust Oncology Research
Fellowship.
9
10
CONFLICT OF INTEREST
None declared.
11
REFERENCES
12
1
2
3
World Health Organization/
International Agency for Research on
Cancer. GLOBOCAN 2008 (Cancer
incidence and mortality worldwide in
2008). Available at: http://globocan.iarc.
fr/. Accessed October 2010
Tominaga S. Cancer incidence in
Japanese in Japan, Hawaii, and western
United States. Natl Cancer Inst Monogr
1985; 69: 83–92
Shimizu H, Ross RK, Bernstein L,
Yatani R, Henderson BE, Mack TM.
Cancers of the prostate and breast
among Japanese and white immigrants
in Los Angeles County. Br J Cancer 1991;
63: 963–6
1356
13
14
15
Khan N, Adhami VM, Mukhtar H.
Review: green tea polyphenols in
chemoprevention of prostate cancer:
preclinical and clinical studies. Nutr
Cancer 2009; 61: 836–41
Cao Y, Cao R, Brakenhielm E.
Antiangiogenic mechanisms of dietderived polyphenols. J Nutr Biochem
2002; 13: 380–90
Johnson JJ, Bailey HH, Mukhtar H.
Green tea polyphenols for prostate
cancer chemoprevention: a translational
perspective. Phytomedicine 2010; 17: 3–
13
Kurahashi N, Sasazuki S, Iwasaki M,
Inoue M, Tsugane S. Green tea
consumption and prostate cancer risk in
Japanese men: a prospective study. Am J
Epidemiol 2008; 167: 71–7
Bettuzzi S, Brausi M, Rizzi F,
Castagnetti G, Peracchia G, Corti A.
Chemoprevention of human prostate
cancer by oral administration of green
tea catechins in volunteers with highgrade prostate intraepithelial neoplasia:
a preliminary report from a one-year
proof-of-principle study. Cancer Res
2006; 66: 1234–40
Jatoi A, Ellison N, Burch PA et al. A
phase II trial of green tea in the
treatment of patients with androgen
independent metastatic prostate
carcinoma. Cancer 2003; 97: 1442–
6
Choan E, Segal R, Jonker D et al. A
prospective clinical trial of green tea for
hormone refractory prostate cancer: an
evaluation of the complementary/
alternative therapy approach. Urol Oncol
2005; 23: 108–13
Usui T. Pharmaceutical prospects of
phytoestrogens. Endocr J 2006; 53: 7–20
Handayani R, Rice L, Cui Y et al. Soy
isoflavones alter expression of genes
associated with cancer progression,
including interleukin-8, in androgenindependent PC-3 human prostate
cancer cells. J Nutr 2006; 136: 75–
82
Goetzl MA, Van Veldhuizen PJ,
Thrasher JB. Effects of soy
phytoestrogens on the prostate. Prostate
Cancer Prostatic Dis 2007; 10: 216–
23
Yan L, Spitznagel EL. Meta-analysis of
soy food and risk of prostate cancer in
men. Int J Cancer 2005; 117: 667–9
Hwang YW, Kim SY, Jee SH, Kim YN,
Nam CM. Soy food consumption and
16
17
18
19
20
21
22
23
24
25
risk of prostate cancer: a meta-analysis
of observational studies. Nutr Cancer
2009; 61: 598–606
Bylund A, Lundin E, Zhang JX et al.
Randomised controlled short-term
intervention pilot study on rye bran
bread in prostate cancer. Eur J Cancer
Prev 2003; 12: 407–15
Kumar NB, Cantor A, Allen K et al. The
specific role of isoflavones in reducing
prostate cancer risk. Prostate 2004; 59:
141–7
Dalais FS, Meliala A,
Wattanapenpaiboon N et al. Effects of
a diet rich in phytoestrogens on
prostate-specific antigen and sex
hormones in men diagnosed with
prostate cancer. Urology 2004; 64: 510–
5
Amir H, Karas M, Giat J et al. Lycopene
and 1,25-dihydroxyvitamin D3
cooperate in the inhibition of cell
cycle progression and induction of
differentiation in HL-60 leukemic cells.
Nutr Cancer 1999; 33: 105–12
Karas M, Amir H, Fishman D et al.
Lycopene interferes with cell cycle
progression and insulin-like growth
factor I signaling in mammary cancer
cells. Nutr Cancer 2000; 36: 101–11
Santillo VM, Lowe FC. Role of vitamins,
minerals and supplements in the
prevention and management of prostate
cancer. Int Braz J Urol 2006; 32: 3–14
Etminan M, Takkouche B, CaamanoIsorna F. The role of tomato products
and lycopene in the prevention of
prostate cancer: a meta-analysis of
observational studies. Cancer Epidemiol
Biomarkers Prev 2004; 13: 340–5
Haseen F, Cantwell MM, O’Sullivan
JM, Murray LJ. Is there a benefit from
lycopene supplementation in men with
prostate cancer? A systematic review.
Prostate Cancer Prostatic Dis 2009; 12:
325–32
Chen L, Stacewicz-Sapuntzakis M,
Duncan C et al. Oxidative DNA damage
in prostate cancer patients consuming
tomato sauce-based entrees as a wholefood intervention. J Natl Cancer Inst
2001; 93: 1872–9
Jatoi A, Burch P, Hillman D et al. A
tomato-based, lycopene-containing
intervention for androgen-independent
prostate cancer: results of a Phase II
study from the North Central Cancer
Treatment Group. Urology 2007; 69:
289–94
©
BJU INTERNATIONAL
©
2 0 11 T H E A U T H O R S
2 0 11 B J U I N T E R N A T I O N A L
PROSTATE CANCER AND DIET
26 Kim HS, Bowen P, Chen L et al. Effects
of tomato sauce consumption on
apoptotic cell death in prostate benign
hyperplasia and carcinoma. Nutr Cancer
2003; 47: 40–7
27 Ansari MS, Gupta NP. Lycopene:
a novel drug therapy in hormone
refractory metastatic prostate
cancer. Urol Oncol 2004; 22: 415–
20
28 Barber NJ, Zhang X, Zhu G et al.
Lycopene inhibits DNA synthesis in
primary prostate epithelial cells in vitro
and its administration is associated with
a reduced prostate-specific antigen
velocity in a phase II clinical study.
Prostate Cancer Prostatic Dis 2006; 9:
407–13
29 Clark PE, Hall MC, Borden LS Jr et al.
Phase I–II prospective dose-escalating
trial of lycopene in patients with
biochemical relapse of prostate cancer
after definitive local therapy. Urology
2006; 67: 1257–61
30 Ansari MS, Gupta NP. A comparison of
lycopene and orchidectomy vs
orchidectomy alone in the management
of advanced prostate cancer. BJU Int
2003; 92: 375–8
31 Schwenke C, Ubrig B, Thurmann P,
Eggersmann C, Roth S. Lycopene
for advanced hormone refractory
prostate cancer: a prospective, open
phase II pilot study. J Urol 2009; 181:
1098–103
32 Kavanaugh CJ, Trumbo PR, Ellwood
KC. The U.S. Food and Drug
Administration’s evidence-based review
for qualified health claims: tomatoes,
lycopene, and cancer. J Natl Cancer Inst
2007; 99: 1074–85
33 Chung FL, Morse MA, Eklind KI, Lewis
J. Quantitation of human uptake of the
anticarcinogen phenethyl isothiocyanate
after a watercress meal. Cancer
Epidemiol Biomarkers Prev 1992; 1: 383–
8
34 Yang CS, Smith TJ, Hong JY.
Cytochrome P-450 enzymes as targets
for chemoprevention against chemical
carcinogenesis and toxicity:
opportunities and limitations. Cancer
Res 1994; 54 (Suppl.): 1982s–1986s
35 Zhang Y, Kensler TW, Cho CG, Posner
GH, Talalay P. Anticarcinogenic
activities of sulforaphane and
structurally related synthetic norbornyl
isothiocyanates. Proc Natl Acad Sci USA
1994; 91: 3147–50
©
36 Hecht SS. Chemoprevention by
isothiocyanates. J Cell Biochem Suppl
1995; 22: 195–209
37 Wang LG, Liu XM, Chiao JW.
Repression of androgen receptor in
prostate cancer cells by phenethyl
isothiocyanate. Carcinogenesis 2006;
27: 2124–32
38 Kolonel LN, Hankin JH, Whittemore
AS et al. Vegetables, fruits, legumes and
prostate cancer: a multiethnic casecontrol study. Cancer Epidemiol
Biomarkers Prev 2000; 9: 795–804
39 Cohen JH, Kristal AR, Stanford JL.
Fruit and vegetable intakes and prostate
cancer risk. J Natl Cancer Inst 2000; 92:
61–8
40 Kristal AR, Lampe JW. Brassica
vegetables and prostate cancer risk: a
review of the epidemiological evidence.
Nutr Cancer 2002; 42: 1–9
41 Giovannucci E, Rimm EB, Liu Y,
Stampfer MJ, Willett WC. A
prospective study of cruciferous
vegetables and prostate cancer. Cancer
Epidemiol Biomarkers Prev 2003; 12:
1403–9
42 Key TJ, Allen N, Appleby P et al. Fruits
and vegetables and prostate cancer: no
association among 1104 cases in a
prospective study of 130544 men in the
European Prospective Investigation into
Cancer and Nutrition (EPIC). Int J Cancer
2004; 109: 119–24
43 Stram DO, Hankin JH, Wilkens LR et al.
Prostate cancer incidence and intake
of fruits, vegetables and related
micronutrients: the multiethnic cohort
study* (United States). Cancer Causes
Control 2006; 17: 1193–207
44 Takachi R, Inoue M, Sawada N et al.
Fruits and vegetables in relation to
prostate cancer in Japanese men: the
Japan Public Health Center-Based
Prospective Study. Nutr Cancer 2010;
62: 30–9
45 Donkena KV, Karnes RJ, Young CY.
Vitamins and prostate cancer risk.
Molecules 2010; 15: 1762–83
46 Omenn GS, Goodman GE, Thornquist
MD et al. Effects of a combination of
beta carotene and vitamin A on lung
cancer and cardiovascular disease. N
Engl J Med 1996; 334: 1150–5
47 Neuhouser ML, Barnett MJ, Kristal AR
et al. Dietary supplement use and
prostate cancer risk in the Carotene and
Retinol Efficacy Trial. Cancer Epidemiol
Biomarkers Prev 2009; 18: 2202–6
48 Lawson KA, Wright ME, Subar A et al.
Multivitamin use and risk of prostate
cancer in the National Institutes of
Health-AARP Diet and Health Study.
J Natl Cancer Inst 2007; 99: 754–64
49 The Alpha-Tocopherol, Beta Carotene
Cancer Prevention Study Group. The
effect of vitamin E and beta carotene on
the incidence of lung cancer and other
cancers in male smokers. The AlphaTocopherol, Beta Carotene Cancer
Prevention Study Group. N Engl J Med
1994; 330: 1029–35
50 Virtamo J, Pietinen P, Huttunen JK
et al. Incidence of cancer and mortality
following alpha-tocopherol and betacarotene supplementation: a
postintervention follow-up. JAMA 2003;
290: 476–85
51 Rodriguez C, Jacobs EJ, Mondul AM,
Calle EE, McCullough ML, Thun MJ.
Vitamin E supplements and risk of
prostate cancer in U.S. Men. Cancer
Epidemiol Biomarkers Prev 2004; 13:
378–82
52 Wright ME, Weinstein SJ, Lawson KA
et al. Supplemental and dietary vitamin E
intakes and risk of prostate cancer in a
large prospective study. Cancer
Epidemiol Biomarkers Prev 2007; 16:
1128–35
53 Gaziano JM, Glynn RJ, Christen WG
et al. Vitamins E and C in the prevention
of prostate and total cancer in men: the
Physicians’ Health Study II randomized
controlled trial. JAMA 2009; 301:
52–62
54 Lippman SM, Klein EA, Goodman PJ
et al. Effect of selenium and vitamin E on
risk of prostate cancer and other
cancers: the Selenium and Vitamin E
Cancer Prevention Trial (SELECT). JAMA
2009; 301: 39–51
55 Chan JM, Gann PH, Giovannucci EL.
Role of diet in prostate cancer
development and progression. J Clin
Oncol 2005; 23: 8152–60
56 Clark LC, Combs GF Jr, Turnbull
BW et al. Effects of selenium
supplementation for cancer prevention
in patients with carcinoma of the skin. A
randomized controlled trial. Nutritional
Prevention of Cancer Study Group. JAMA
1996; 276: 1957–63
57 Brinkman M, Reulen RC, Kellen E,
Buntinx F, Zeegers MP. Are men with
low selenium levels at increased risk of
prostate cancer? Eur J Cancer 2006; 42:
2463–71
2 0 11 T H E A U T H O R S
BJU INTERNATIONAL
©
2 0 11 B J U I N T E R N A T I O N A L
1357
H O R I ET AL.
58 Marshall JR. Randomized phase III trial
of selenium supplementation to prevent
prostate cancer among men with high
grade prostatic intraepithelial neoplasia.
Paper presented at the 2010 American
Urological Association (AUA) Annual
Meeting; June 1, 2010; San Francisco,
USA
59 Chan JM, Oh WK, Xie W et al. Plasma
selenium, manganese superoxide
dismutase, and intermediate- or highrisk prostate cancer. J Clin Oncol 2009;
27: 3577–83
60 Giovannucci E, Rimm EB, Wolk A et al.
Calcium and fructose intake in relation
to risk of prostate cancer. Cancer Res
1998; 58: 442–7
61 Miller GJ. Vitamin D and prostate
cancer: biologic interactions and clinical
potentials. Cancer Metastasis Rev 1998;
17: 353–60
62 Zhao XY, Feldman D. The role of
vitamin D in prostate cancer. Steroids
2001; 66: 293–300
63 Polek TC, Weigel NL. Vitamin D and
prostate cancer. J Androl 2002; 23: 9–
17
64 Stewart LV, Weigel NL. Vitamin D and
prostate cancer. Exp Biol Med (Maywood)
2004; 229: 277–84
65 Beer TM, Myrthue A. Calcitriol in the
treatment of prostate cancer. Anticancer
Res 2006; 26: 2647–51
66 Moreno J, Krishnan AV, Peehl DM,
Feldman D. Mechanisms of vitamin Dmediated growth inhibition in prostate
cancer cells: inhibition of the
prostaglandin pathway. Anticancer Res
2006; 26: 2525–30
67 Chan JM, Stampfer MJ, Ma J et al.
Insulin-like growth factor-I (IGF-I) and
IGF binding protein-3 as predictors of
advanced-stage prostate cancer. J Natl
Cancer Inst 2002; 94: 1099–106
68 Gunnell D, Oliver SE, Peters TJ et al.
Are diet–prostate cancer associations
mediated by the IGF axis? A crosssectional analysis of diet, IGF-I and
IGFBP-3 in healthy middle-aged men. Br
J Cancer 2003; 88: 1682–6
69 Pollak MN, Schernhammer ES,
Hankinson SE. Insulin-like growth
factors and neoplasia. Nat Rev Cancer
2004; 4: 505–18
70 Gao X, LaValley MP, Tucker KL.
Prospective studies of dairy product and
calcium intakes and prostate cancer risk:
a meta-analysis. J Natl Cancer Inst 2005;
97: 1768–77
1358
71
72
73
74
75
76
77
78
79
80
81
Qin LQ, Xu JY, Wang PY, Tong J, Hoshi
K. Milk consumption is a risk factor for
prostate cancer in Western countries:
evidence from cohort studies. Asia Pac J
Clin Nutr 2007; 16: 467–76
Huncharek M, Muscat J, Kupelnick B.
Dairy products, dietary calcium and
vitamin D intake as risk factors for
prostate cancer: a meta-analysis of
26,769 cases from 45 observational
studies. Nutr Cancer 2008; 60: 421–41
Carmody J, Olendzki B, Reed G,
Andersen V, Rosenzweig P. A dietary
intervention for recurrent prostate
cancer after definitive primary
treatment: results of a randomized pilot
trial. Urology 2008; 72: 1324–8
Rose DP, Connolly JM. Effects of fatty
acids and eicosanoid synthesis inhibitors
on the growth of two human prostate
cancer cell lines. Prostate 1991; 18: 243–
54
Pandalai PK, Pilat MJ, Yamazaki K,
Naik H, Pienta KJ. The effects of
omega-3 and omega-6 fatty acids on in
vitro prostate cancer growth. Anticancer
Res 1996; 16: 815–20
Karmali RA, Reichel P, Cohen LA et al.
The effects of dietary omega-3 fatty
acids on the DU-145 transplantable
human prostatic tumor. Anticancer Res
1987; 7: 1173–9
Rose DP, Cohen LA. Effects of dietary
menhaden oil and retinyl acetate on the
growth of DU 145 human prostatic
adenocarcinoma cells transplanted into
athymic nude mice. Carcinogenesis
1988; 9: 603–5
Berquin IM, Min Y, Wu R et al.
Modulation of prostate cancer
genetic risk by omega-3 and omega-6
fatty acids. J Clin Invest 2007; 117:
1866–75
Brown MD, Hart C, Gazi E, Gardner P,
Lockyer N, Clarke N. Influence of
omega-6 PUFA arachidonic acid and
bone marrow adipocytes on metastatic
spread from prostate cancer. Br J Cancer
2010; 102: 403–13
Wang MT, Honn KV, Nie D.
Cyclooxygenases, prostanoids, and
tumor progression. Cancer Metastasis
Rev 2007; 26: 525–34
Needleman P, Raz A, Minkes MS,
Ferrendelli JA, Sprecher H. Triene
prostaglandins: prostacyclin and
thromboxane biosynthesis and unique
biological properties. Proc Natl Acad Sci
USA 1979; 76: 944–8
82 Bagga D, Wang L, Farias-Eisner R,
Glaspy JA, Reddy ST. Differential
effects of prostaglandin derived from
omega-6 and omega-3 polyunsaturated
fatty acids on COX-2 expression and IL-6
secretion. Proc Natl Acad Sci USA 2003;
100: 1751–6
83 Terry P, Lichtenstein P, Feychting M,
Ahlbom A, Wolk A. Fatty fish
consumption and risk of prostate cancer.
Lancet 2001; 357: 1764–6
84 Augustsson K, Michaud DS, Rimm EB
et al. A prospective study of intake of fish
and marine fatty acids and prostate
cancer. Cancer Epidemiol Biomarkers
Prev 2003; 12: 64–7
85 Leitzmann MF, Stampfer MJ, Michaud
DS et al. Dietary intake of n-3 and n-6
fatty acids and the risk of prostate
cancer. Am J Clin Nutr 2004; 80:
204–16
86 Terry PD, Rohan TE, Wolk A. Intakes of
fish and marine fatty acids and the risks
of cancers of the breast and prostate and
of other hormone-related cancers: a
review of the epidemiologic evidence.
Am J Clin Nutr 2003; 77: 532–43
87 Demark-Wahnefried W, Price DT,
Polascik TJ et al. Pilot study of dietary
fat restriction and flaxseed
supplementation in men with prostate
cancer before surgery: exploring the
effects on hormonal levels, prostatespecific antigen, and histopathologic
features. Urology 2001; 58: 47–52
88 Demark-Wahnefried W, Polascik TJ,
George SL et al. Flaxseed
supplementation (not dietary fat
restriction) reduces prostate cancer
proliferation rates in men presurgery.
Cancer Epidemiol Biomarkers Prev 2008;
17: 3577–87
89 Kolonel LN. Fat, meat, and prostate
cancer. Epidemiol Rev 2001; 23: 72–81
90 Barnard RJ, Ngo TH, Leung PS,
Aronson WJ, Golding LA. A low-fat diet
and/or strenuous exercise alters the IGF
axis in vivo and reduces prostate tumor
cell growth in vitro. Prostate 2003; 56:
201–6
91 Dennis LK, Snetselaar LG, Smith BJ,
Stewart RE, Robbins ME. Problems
with the assessment of dietary fat in
prostate cancer studies. Am J Epidemiol
2004; 160: 436–44
92 World Cancer Research Fund/
American Institute for Cancer
Research. Food, Nutrition, Physical
Activity and the Prevention of Cancer: a
©
BJU INTERNATIONAL
©
2 0 11 T H E A U T H O R S
2 0 11 B J U I N T E R N A T I O N A L
PROSTATE CANCER AND DIET
93
94
95
96
97
98
99
100
101
102
103
104
©
Global Pespective. Washington DC: AICR,
2007
Park SY, Murphy SP, Wilkens LR,
Henderson BE, Kolonel LN. Fat and
meat intake and prostate cancer risk: the
multiethnic cohort study. Int J Cancer
2007; 121: 1339–45
Neuhouser ML, Barnett MJ, Kristal AR
et al. (n-6) PUFA increase and dairy foods
decrease prostate cancer risk in heavy
smokers. J Nutr 2007; 137: 1821–7
Crowe FL, Key TJ, Appleby PN et al.
Dietary fat intake and risk of prostate
cancer in the European Prospective
Investigation into Cancer and Nutrition.
Am J Clin Nutr 2008; 87: 1405–13
Ornish D, Weidner G, Fair WR et al.
Intensive lifestyle changes may affect
the progression of prostate cancer. J Urol
2005; 174: 1065–70
Elia M, Cummings JH. Physiological
aspects of energy metabolism
and gastrointestinal effects of
carbohydrates. Eur J Clin Nutr 2007; 61
(Suppl. 1): S40–74
Bidoli E, Talamini R, Bosetti C et al.
Macronutrients, fatty acids, cholesterol
and prostate cancer risk. Ann Oncol
2005; 16: 152–7
Venkateswaran V, Haddad AQ,
Fleshner NE et al. Association of
diet-induced hyperinsulinemia with
accelerated growth of prostate cancer
(LNCaP) xenografts. J Natl Cancer Inst
2007; 99: 1793–800
Freedland SJ, Mavropoulos J, Wang A
et al. Carbohydrate restriction, prostate
cancer growth, and the insulin-like
growth factor axis. Prostate 2008; 68:
11–9
Mavropoulos JC, Buschemeyer WC III,
Tewari AK et al. The effects of varying
dietary carbohydrate and fat content on
survival in a murine LNCaP prostate
cancer xenograft model. Cancer Prev Res
(Phila) 2009; 2: 557–65
Lin DW, Neuhouser ML, Schenk JM
et al. Low-fat, low-glycemic load diet
and gene expression in human prostate
epithelium: a feasibility study of using
cDNA microarrays to assess the response
to dietary intervention in target tissues.
Cancer Epidemiol Biomarkers Prev 2007;
16: 2150–4
Zheng W, Lee SA. Well-done meat
intake, heterocyclic amine exposure, and
cancer risk. Nutr Cancer 2009; 61: 437–
46
Knize MG, Felton JS. Formation and
105
106
107
108
109
110
111
112
113
114
human risk of carcinogenic heterocyclic
amines formed from natural precursors
in meat. Nutr Rev 2005; 63: 158–65
Shirai T, Sano M, Tamano S et al. The
prostate: a target for carcinogenicity of
2-amino-1-methyl-6phenylimidazo[4,5-b]pyridine (PhIP)
derived from cooked foods. Cancer Res
1997; 57: 195–8
Cross AJ, Peters U, Kirsh VA et al.
A prospective study of meat and meat
mutagens and prostate cancer risk.
Cancer Res 2005; 65: 11779–84
Koutros S, Cross AJ, Sandler DP et al.
Meat and meat mutagens and risk of
prostate cancer in the Agricultural
Health Study. Cancer Epidemiol
Biomarkers Prev 2008; 17: 80–7
Norrish AE, Ferguson LR, Knize MG,
Felton JS, Sharpe SJ, Jackson RT.
Heterocyclic amine content of
cooked meat and risk of prostate
cancer. J Natl Cancer Inst 1999; 91:
2038–44
Richman EL, Stampfer MJ, Paciorek A,
Broering JM, Carroll PR, Chan JM.
Intakes of meat, fish, poultry, and
eggs and risk of prostate cancer
progression. Am J Clin Nutr 2010; 91:
712–21
Barnes PM, Bloom B, Nahin RL.
Complementary and Alternative
Medicine Use Among Adults and
Children: United States, 2007. CDC
National Health Statistics Report #12,
December 10, 2008. Available at:
http://www.cdc.gov/nchs/data/nhsr/
nhsr012.pdf. Accessed October 2010
Lowe FC, Patel T. Complementary and
alternative medicine in urology: what we
need to know in 2008. BJU Int 2008;
102: 422–4
Hoffmann I. Transcending reductionism
in nutrition research. Am J Clin Nutr
2003; 78 (Suppl.): 514S–6S
Khan N, Afaq F, Mukhtar H. Lifestyle
as risk factor for cancer: evidence from
human studies. Cancer Lett 2010; 28:
133–43
Moyad MA, Lowe FC. Educating
patients about lifestyle modifications for
prostate health. Am J Med 2008; 121:
S34–42
Correspondence: Satoshi Hori, Department of
Uro-oncology, University of Cambridge,
Hutchison/MRC Research Centre, Cambridge,
UK.
e-mail: [email protected]
Abbreviations: AR, androgen receptor;
ATBC, α-tocopherol, β-carotene
cancer prevention study; COX-2,
cyclooxygenase-2; CRPC, castrationresistant prostate cancer; FDA, the USA
Food and Drug Administration; HCA,
heterocyclic amine; HGPIN, high-grade
prostatic intraepithelial neoplasia; IGF,
insulin-like growth factor; NIH, the
National Institutes of Health; OR, odds
ratio; PUFA, polyunsaturated fatty acids;
RCT, randomised controlled trial; RR,
relative risk; RP, radical prostatectomy;
SELECT, Selenium and Vitamin E Cancer
Prevention Trial.
EDITORIAL COMMENT
PROSTATE CANCER AND DIET: FOOD
FOR THOUGHT?
In the above review Hori et al. discuss the
complex relationship between dietary
composition and prostate cancer prevention
and progression. Using a literature review
comprising primarily of randomized control
trials, the authors summarized key topics
relevant to prostate cancer.
The role of diet and cancer is complicated,
as a diet is composed of both macro- and
micronutrients. However, people do not eat
nutrients; they eat whole foods such as
chicken, vegetables, or fruits. These foods may
also contain minerals and be a source of
compounds known as phytochemicals. Diet is
also composed of calories. Thus, determining
which specific factors are linked with cancer is
not easy and indeed this may explain the
often ‘negative’ findings between diet and
prostate cancer, although some common
patterns are starting to emerge.
The authors nicely review the role of
phytochemicals in green tea, soy, and
cruciferous vegetables. While the molecular
structure of each compound is distinctly
different, all share similar antioxidant and
anti-inflammatory properties that decrease
DNA damage caused by reactive oxygen
species and increase apoptosis in cancer cells
[1]. Therefore, we suggest perhaps the source
of phytochemicals is less important than the
amount of overall consumption.
For macronutrients, preclinical data suggest
there may be a bell-shaped relationship
2 0 11 T H E A U T H O R S
BJU INTERNATIONAL
©
2 0 11 B J U I N T E R N A T I O N A L
1359