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The role of plant-based nutrition in cancer prevention
Mariah Madigan1, Elisa Karhu2
1Northern Ontario School of Medicine, Sudbury P3E 2C6 , Canada .
2Universit y of Miami Miller School of Medicine, Miami 33136, USA.
Correspondence to: Dr. Mariah Madigan, Northern Ontario School of Medicine, 935 Ramsey Lake Rd Sudbury, Sudbury P3E 2C6,
Canada. E-mail: email@example.com
How to cite this article: Madigan M, Karhu E. The role of plant-based nutrition in cancer prevention.
J Unexplored Med Data
8 Jul 2018 Fir
9 Jul 2018 Revised: 24 Oct 2018 Accepted
24 Oct 2018 Published
8 Nov 2018
Science Editor: Tarek Shalaby Copy Editor: Cui Yu Production Editor: Zhong-Yu Guo
Plant-based nutrition has been shown to protect against the 15 leading causes of death in the world, including many
cancers, and may offer beneﬁts as a disease modifying tool to improve the management and treatment of these conditions.
Results on the effects of plant-based nutrition on breast, prostate, colorectal and gastrointestinal cancers have been the
most extensively studied, and thus have the most published supporting evidence thus far. Whole foods plant-based diets
have shown to signiﬁcantly protect against these cancers, as well as additional cancers and other chronic disease states.
Nutritional interventions in the prevention of various cancers offer a signiﬁcant beneﬁt to currently used medical therapies,
and should be employed more often as an adjunct to ﬁrst-line medical therapy. Although the effects of diet are becoming
more well-known and the role of diet and lifestyle factors in health and disease is gaining more attention and emphasis, the
beneﬁts or detriments are still underestimated and undervalued.
Vegan nutrition, plant-based diet, cancer, nutritional therapy
In the United States and many other industrialized countries, the main causes of death are preventable.
In particular, our diet remains the number-one cause of premature death and the number-one cause of dis-
ability. Populations consuming diets of mostly plant-based foods have been characterized by a marked
reduction in mortality and age-adjusted incidence of many cancers common in Western society. These
cancers include breast, prostate, colon, pancreas, ovary, and uterine endometrium cancers[3, 4]. However, this
phenomenon is becoming less prominent as the Westernized diet and lifestyle spread throughout the world.
Reports by the International Agency for Research on Cancer, the cancer agency of the World Health Orga-
nization implicate red and processed meats as important carcinogens. In contrast, other nutritional aspects
such as high intake of ber, fruits and vegetables have a protective eect on cancer[6-9]. While the importance
of plant-based foods such as fruits, vegetables, nuts, seeds, and legumes as sources of nutrients is generally
accepted, utilization of diet for prevention and management of disease is still uncommon. is is despite the
fact that multiple observational and experimental research studies have demonstrated a signicant protective
eect of plant-based diets against the incidence of cancer as well as many other disease conditions includ-
ing the 15 leading causes of death in the western world . A recent comprehensive meta-analysis reported a
signicant protective eect of a vegetarian diet vs. the incidence from total cancer (-8%) while a vegan diet
conferred a signicant reduced risk (-15%) of incidence from total cancer.
Current treatment options for cancer include surgery, radiotherapy, and chemotherapy. These cancer
treatments impose a large nancial burden not only on health care systems but also to patients themselves.
erefore, nutritional interventions should be used for prevention and could serve as a cost-eective and
safe adjunct therapy to standard medical treatments. This review explores the existing evidence of the
inuence of diet on cancer incidence and progression with a specic focus on the eects of a reduction or
total elimination of animal protein, in addition to notable bioactive compounds in plant foods that offer
protection against cancers. Though plant-based nutrition has been shown to help prevent and improve
survival in many cancers, our review will focus mainly on breast, prostate, colorectal and gastrointestinal (GI)
cancers, since these are the classes that have the most supporting evidence for plant-based diets to date. We
will also briey touch on “other” cancers before our concluding section.
A PubMed search was conducted using terms such as vegan diet and cancer, vegetarian diet and cancer,
plant-based nutrition and cancer, vegan diet and breast cancer, vegan diet and prostate cancer, vegan diet
and GI cancer. Secondary search strategy included cross referencing articles as well as identifying potential
resources from the Physicians Committee for Responsible Medicine nutrition guide for clinicians. Sources
included systematic reviews and meta-analyses, as well as original studies with various methodologies such
as longitudinal prospective cohort studies, randomized controlled trials, and case series.
PLANT-BASED NUTRITION AND BREAST CANCER
Next to skin cancer, the most common cancer among American women is breast cancer. Each year an
estimated 250,000 are diagnosed (in addition to 2,500 cases in men), and 40,000 women as well as 460 men
die from it. Typically, imaging and early detection is emphasized in order to improve survival. However,
early detection and screening does not prevent breast cancer, it simply picks up disease that already exists.
Furthermore, modern imaging isn’t good enough to detect cancer’s earliest stages, thus what has come to be
described by the medical community as “early detection”, is unfortunately actually “late detection”. For
example, a breast cancer tumor must be the size of about 2 billion cells (30 doublings) in order to get picked
up by a mammogram[15 ,16 ]. The main factor that determines doubling time, and thus the timing of when
someone gets diagnosed with cancer, can range from 25 days to over a thousand days. is means that
someone could be diagnosed anywhere between 2 and 100 years, and a primary determination as to where
an individual falls on that timeline, may depend on what they eat.
Based on autopsy studies, as many as 39% of women in their 40’s already have developed breast cancers
that may simply be too small to detect by mammograms[19 , 20] . Breast cancers may even begin developing in
utero due to a mother’s diet. Thus, waiting until diagnosis to start eating and living healthier, might be
too late. Typically, someone is considered to be “healthy” if they haven’t shown to have any pathologies or
abnormalities on scans/diagnostic screening tests, and if they don’t show any clinical symptoms of a disease
state. However, if someone has been harbouring a malignancy for decades that was simply too small to be
detected or to lead to signicant noticeable clinical signs, can that individual truly be considered “healthy”?
Since there is much more going on at a cellular level within the human body than scans may ever be able to
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fully demonstrate, a more benecial framework may be to look at living in a constant state of prevention and
treatment, rather than waiting until a disease has progressed to the point of showing outward signs. erefore,
perhaps we should be living as if we already have the beginnings of disease in our bodies, because a diet and
lifestyle of prevention may also be one of treatment for the potential occult diseases that we cannot yet see.
In 2014, the American Institute for Cancer Research (AICR) came up with 10 recommendations for cancer
prevention[2 2]. e conclusion around diet was that the intake of primarily whole plant foods (vegetables,
fruits, whole grains, beans) decreases the risk of many cancers and other disease states. Looking at breast
cancer specifically, a 2013 study that followed approximately 30,000 post-menopausal women with
no history of breast cancer for 7 years showed that by achieving just 3 of 10 AICR recommendations
(maintaining a normal body weight, limiting alcohol, and eating mostly plant-based), a 62% decreased risk
of breast cancer was achieved. Additionally, the rate at which eating plant-based can change an individual’s
physiology is quite remarkable. In 2006, the effects of a healthy diet (plant-based) and lifestyle (walking
every day) on tumor cell growth and apoptosis in vitro were tested. Researchers found that within only
2 weeks of healthy living, participants blood samples were able to suppress cancer growth and kill 20%-
30% more malignant cells than blood samples taken prior to the diet/lifestyle change. It was concluded that
the cancer suppression effect could be attributed to decreased levels of insulin-like growth factor 1 (IGF-1)
due to reduced intake of animal protein[25 ,26]. IGF-1 is a hormone crucial for cell growth, and the more IGF-1
presents in the blood stream, the higher ones risk for cancer development. erefore, it is hypothesized that
by reducing animal intake, we reduce IGF-1 and boost our body’s natural cancer defences. In 2002, Ngo
and colleagues found that aer 11 days of reducing animal protein consumption, levels of circulating IGF-1
dropped by 20%, whereas levels of the cancer protective IGF-1 binding protein increased by 50%. In terms
of how much the intake of animal proteins must be reduced in order to obtain these protective eects, it
is only those following a fully plant-based (vegan) diet that experience cancer protection due to decreased
growth hormone and increased binding protein levels. Vegetarians who consume eggs and dairy do not have
the same protective eect, because all animal proteins stimulate the production of IGF-1, regardless of if the
source is from the muscle, eggs, or dairy[26 ,2 9].
Heterocyclic amines and breast cancer
Another substance besides IGF-1 that is found in animal products and contributes to cancer risk is hetero-
cyclic amines (HCAs). Since an original paper in 1939, it has been found that cancer producing substances
are present in animal products cooked in various forms at high temperatures (roasting, pan-frying, grill-
ing, baking)[30 ]. HCAs are described by the National Cancer Institute as “chemicals found when muscle
in meat, including beef, pork, sh, and poultry, is cooked using high-temperature methods”. HCAs are
formed when these high temperatures promote chemical reactions between components of muscle tissue,
compounds that are lacking in plants and thus cooked veggie burgers/products do not contain measurable
amounts of HCAs. e longer the meat is cooked, the more HCAs produced, and results show that well-
done meat is associated with increased risk of breast, colon, esophagus, pancreas, prostate and stomach.
is however, does not mean that less cooking time doesn’t produce HCAs, and even baking chicken for
15 min at 350 degrees leads to the production of measurable amounts that lead to DNA damage and thus an
increased risk for cancer development[34, 35].
A number of studies, including the Long Island Breast Cancer Study Project and the Iowa Women’s Health
Study have demonstrated signicant correlation between women eating more cooked meats and higher odds
of developing breast cancer[36 ,37]. e Long Island study saw a 47% increased odds in women who ate more
grilled, barbecue, or smoked meat across their lifetime, and the Iowa study saw a 5-fold increased odds of
cancer occurrence in women who ate their meat “well-done”. Studies have also shown a link between the
amount of DNA damage in the breast tissue and fried meat consumption. One mechanism behind this
increased odds of breast cancer is that 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), the most
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abundant HCA in cooked meat, has potent estrogen-like eects and can contribute to cell growth almost as
much as endogenous estrogen which is the hormone responsible for feeding most human breast cancer tu-
mours[3 9]. Aer initial in vitro studies, in order to determine if HCAs actually make their way into women’s
breast ducts from their food, researchers measured levels of PhIP in subject’s breast milk, and amounts were
detected in concentrations known to be carcinogenic. In another study, PhIP was found in hair samples of
both meat-eating and vegetarian women, since HCAs are also found in other forms of animal proteins than
just muscle tissue, such as fried eggs. erefore, in order to be protected from PhIP and other HCAs, eat-
ing a fully plant-based diet appears safest.
Preventing breast cancer with eating plants
Unfortunately, even post breast cancer diagnosis, most don’t adopt the necessary dietary and lifestyle changes
to combat their disease and prolong life, notably consuming more whole plant foods. is is for various
reasons ranging from lack of personal realization, failure of physicians to educate their patients or be educated
enough themselves in the field of nutrition to accurately and adequately counsel patients on nutritional
interventions for disease states. Making a couple simple changes, such as consuming just 5 or more servings of
fruits and vegetables per day along with walking 30 min 6 days a week is shown to lead to a notable survival
advantage, with 50% less risk of 2-year post-diagnosis mortality rates.
Some of the notable plant foods/components of plant foods that are particularly beneficial include fiber,
greens, and flaxseeds. Studies have shown that women consuming 6 g or more of soluble fiber a day
(equivalent of a cup of black beans) had a 62% risk reduction of breast cancer compared to those consuming
less than 4 g. Notably, the effects seem to be more significant for the harder to treat estrogen receptor
negative (ER-) tumors, where premenopausal women with high ber intake had an 85% risk reduction.
Dozens of reports including case control and prospective cohort studies have reported similar findings,
with the consensus being that the more plant-based one’s diet, the better for one’s health[45,4 6]. Results have
associated every 20 g of ber consumed per day with approximately a 15% risk reduction of breast cancer,
however some suggest that the eects may only be achieved once a baseline of 20 g per day is achieved.
One might think that 20 g may not seem like very much, given that just one cup of split peas has 16 g, yet
the average American women generally gets less than 15 g per day, with vegetarians slightly higher at 20 g,
healthy vegetarians at 37 g, vegans at 46 g, and whole-food plant-based diets recommended as therapeutic
interventions for many chronic disease averaging about 60 g[48- 50]. These results paint a clear picture that
individuals in America and Westernized countries around the world are ber decient, and an increase in
ber intake from whole foods (not supplements) can be of great benet in improving health.
In the above mentioned Long Island women’s study where cooked meat consumption was linked to a 47%
increased risk of breast cancer, those who also had low intake of fruits and vegetables, had a 74% increased
risk. Higher fruit and vegetable intake is not only associated with better health and lifestyle habits overall,
but there are many bioactive compounds in fruits and vegetables that protect against cancer. For example,
cruciferous vegetables like broccoli boost the activity of detoxifying enzymes in the liver. Research has
shown that consumption of broccoli and brussels sprouts causes increased caffeine clearance, and it was
discovered that the same happens with carcinogens. When feeding non-smokers pan-fried meat for 2 weeks
in addition to 3 cups of broccoli and brussels sprouts, and measuring levels of HCAs in urine samples, liver
clearance was increased. Although consuming the same amount of carcinogens, signicantly less came
out in subject’s urine, a nding consistent with the theory of cruciferous vegetables detoxifying ability. It
was also found that liver function remained enhanced for up to 2 weeks aer vegetable consumption ceased.
However, choosing the veggie burger with no HCAs to detoxify in the rst place is the safest option.
Next, axseeds, one of the rst things considered to be health food, known for their rich source of omega-3
fatty acids, are also signicant as a health product because of their lignan content, which is about 100 times
more than other plant foods[54-56]. Lignans are a class of phytoestrogens that like other phytoestrogens,
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modulate and suppress eects of endogenous estrogen, which is why they are used as a rst line therapy for
menstrual breast pain.
Regarding breast cancer risk, consumption of approximately one tablespoon of ground axseed daily can
extend a women’s menstrual cycle by about a day, meaning less lifetime estrogen exposure and less risk
of breast cancer. In terms of the biological action of axseeds, they actually contain lignan precursors,
which then get activated by intestinal bacteria, a nding that may explain in part why women with frequent
urinary tract infections and thus increased antibiotic consumption (killing natural as well as pathological
gut ora) have higher risk of breast cancer.
In vitro as well as interventional studies have shown lignans to directly suppress the growth and proliferation
of breast cancer cells. In a 2010 National Cancer Institute funded study of 45 women with high breast
cancer risk (due to either suspicious biopsies or previous breast cancer diagnoses) given 2 tablespoons of
ground axseed per day, their cancer risk was found to be greatly reduced. Compared to pre-study, needle
biopsies post yearlong study showed fewer precancerous changes than before, and 80% had decreased levels
of Ki-67, a biomarker for increased cell proliferation, suggesting that breast cancer risk can be signicantly
reduced by just adding a few tablespoons of ground axseeds to one’s food each day. In considering women
already diagnosed with breast cancer, women with higher serum lignan levels[61,62] and who consume more
dietary lignans show increased survival rates. Researchers hypothesize that this nding may be a result of
the concurrent rise of the protein endostatin, which plays a role in starving tumors of their blood supply in
the breasts of women who consume more lignans.
Because of positive preliminary studies with axseeds, randomized, double blind, placebo controlled trials
were developed to test this treatment for breast cancer patients. Flaxseeds are one of the few food items that
have ever been rigorously tested in clinical trials. e study population consisted of women scheduled for
breast cancer surgery, divided into the experimental group, consuming one axseed containing mun each
day, and a control group consuming a placebo mun without axseeds that looked and tasted the same.
Based on tumor biopsies taken about 5 weeks before, and then aer surgery, women in the axseed group
showed decreased tumor proliferation, increased cancer cell death rate, and lower c-erB2 scores which
is a marker of cancer aggressiveness. Therefore, flaxseeds appeared to make tumors less aggressive and
researchers concluded that “dietary axseed has the potential to reduce tumor growth in patients with breast
cancer”. Despite the promising results there has been a lack of translation of these ndings and other studies
showing similar results into clinical practice.
Soy and breast cancer
One way researchers discovered the effects of soy on breast cancer risk, is through population studies.
It has been found that women in Asia are about 5 times less likely to develop breast cancer than North
Americans. Possible explanations may include green tea consumption which is known to decrease risk
by about 30%, as well as increased mushroom consumption. White mushrooms have been shown to
block estrogen synthase enzymes in vitro, and researchers found that when comparing 1000 breast cancer
patients to the same number of healthy controls, those who ate more than just one half of a mushroom
per day experienced a 64% risk reduction over women who ate no mushrooms. erefore, in combination
with drinking half of a tea bag of green tea per day, eating mushrooms leads to a 90% risk reduction.
Furthermore, another factor accounting for the population discrepancies in breast cancer risk is increased
soy consumption throughout the lifespan beginning in childhood in Asian individuals. Lifelong soy
consumption oers the most protective eect, reducing breast cancer risk by 50%, compared to only a 25%
risk reduction if soy is consumed beginning in adulthood[70 ].
e specic compound in soy that is signicant in creating its breast cancer protection are isoavones, a
class of phytoestrogens. There is a common misconception that since estrogen is in word phytoestrogen,
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these compounds have estrogen-like eects, which is not entirely true. ough phytoestrogens bind to the
same receptors as endogenous estrogen, they have a weaker eect and thus actually act to block the eects
of more powerful endogenous and animal product derived estrogen. Of the human body’s two kinds of
estrogen receptors (ERs), endogenous estrogen has stronger anity for alpha receptors, and phytoestrogens
(plant estrogens) for beta receptors. Because of the distribution of alpha and beta receptors in various
tissues, estrogens (and phytoestrogens) have dierent eects depending on receptor distribution in tissues.
For example, estrogen has positive eects on the bones, but contributes to increased risk of breast cancer.
For this reason, ideally the body would benet from a selective ER modulator, allowing positive estrogenic
eects in some tissues (bones), and anti-estrogen eects in others (breast). Phytoestrogens appear to act in
that way[73 ], and soy for example, lowers breast cancer risk (an anti-estrogenic eect) yet reduces menopausal
symptoms such as hot ashes (a pro-estrogenic eect)[74, 75].
In addition to preventing breast cancer, a number of studies have looked at soy consumption of breast
cancer survivors. A meta-analysis of cohort studies showed that increased survival rates and lower cancer
recurrence rates were found in women with the greatest soy consumption. A 2012 study showed that of
the patients who ate the most phytoestrogens post diagnosis, the 5-year survival rate was 90%, compared to
50% in those who did not consume much soy. It was suggested that just a single cup of soymilk contains
enough phytoestrogens to decrease recurrence risk by 25%. Notably, this nding was present in women
with both ER+ and ER- tumors, and was not age dependent.
Another hypothesis as to the mechanism of action of the protective effects of soy’s isoflavones is in its
ability to reactivate BRCA genes. BRCA1 and BRCA2 are known as caretaker genes, suppressing cancer and
repairing DNA, which is why mutations in these genes increase the odds of developing breast cancer[79 ].
However, though genetics do play a role and many individuals believe that the majority of breast cancers
are due to a family history, only 2.5% of cases are actually genetically linked[8 0]. Perhaps the reason that
breast cancers seem to run in families more often than is explained by genetics, is because dietary and
lifestyle habits tend to run in families. Thus, since most patients have functional BRCA genes, cancer in
those individuals is promoted and spread through methylation, a process that suppresses gene expression
and turns o the cancer regulating BRCA genes[8 1]. e mechanism by which isoavones appear to protect
against cancer growth and spread is by their ability to turn suppressed BRCA genes back on through
demethylation, and it is estimated to take only about 1 cup of soybeans to obtain enough phytoestrogens to
alter gene expression[79 ]. Furthermore, in addition to cancers that are BRCA related, soy can also benet those
with M DM2 and CY P1B1 genetic forms of breast cancer, and thus increased soy intake may be of benet to
women with increased genetic risk of any breast cancer, whether genetically caused or not.
PLANT-BASED NUTRITION AND PROSTATE CANCER
It is estimated that in 2018, approximately 1,735,350 new cases of prostate cancer will be diagnosed, 609,640
will die from the disease. Additionally, based on autopsy studies, approximately 50% of men over 80 years
of age die with prostate cancer, not yet knowing they had it. A number of dietary components have been
implicated in prostate cancer risk, and just like in breast cancer, the contributing food sources are of animal
origin. For prostate cancer, this is particularly milk and eggs.
Dairy and prostate cancer
Dairy products are oen advertised as “natural”, yet humans are the only species who consume milk aer
weaning, let alone drink the milk of another species. Advertising also promotes milk and other dairy as
“good” for the body, yet every animal derived food product contains high levels of sex steroid hormones,
especially in dairy due to the fact that milk is taken from lactating female cows. Even hormone levels
in so called “organic” cows have levels high enough to influence hormone related conditions including
acne, reproductive dysfunction, premature puberty, and higher rates of twins[86 -89]. In looking at cancer in
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particular, the concern lies with the effects of growth hormones in addition to sex steroid hormones.
When considering that cow milk is meant to cause a calf to gain a couple hundred pounds within a few
months, it makes sense that a lifetime of human exposure to those growth factors could contribute to
developing cancer, and particularly hormone sensitive tumors[91,92].
The first population studies that prompted concerns linking dairy and cancer were during World War II
when Japanese men were found to have a 25-fold increase incidence of prostate cancer, a nding/trend that
coincided with a 7-fold, 9-fold, and 20-fold increase in egg, meat, and dairy consumption respectively.
Similar trends were also observed in other countries around the world at that time. Numerous case
control and cohort studies then conrmed that consuming cow’s milk is a risk factor for prostate cancer, and
additionally, that the consumption of any dairy product, not just milk, increases prostate cancer risk[95 -9 7].
Experimental tests demonstrated that dripping even organic milk on human prostate cancer cells resulted
in a more than 30% increase in cancer growth compared to a 30% suppression when almond milk was
tested[92,9 8]. Furthermore, observational studies and animal research has indicated that in addition to cancer
risk, dairy consumption may contribute to other negative health eects, including overall mortality rates[99-10 2].
Eggs, choline, and prostate cancer
When prostate cancer is caught early, while cancer cells are localized to the prostate gland, the 5-year
survival rate is nearly 100%, yet when metastasis occurs, it can be as low as 33% . Given this signicant
discrepancy, researchers aim to determine factors that contribute to its spread. To study dietary factors that
may lead to prostate cancer progression, Harvard University researchers followed over 1000 men with early
state prostate cancer for a number of years. In comparison to men who rarely ate eggs, those who ate even
a single egg or less per day had a 2-fold increased risk of metastasis. Even worse than eggs, was poultry, with
regular consumption being linked to a 4-fold increase in risk for metastasis. One hypothesis to explain these
ndings has to do with HCAs, similar to that in breast cancer, which seems to build up in the muscle tissue
of poultry more than other animals. Researchers determined that the substance in eggs responsible for cancer
promotion, is choline, a product concentrated in eggs. Choline is converted into a toxin called trimethylamine
by bacteria present in individuals who consume animal protein and is linked to higher risk of myocardial
infarction, cerebrovascular events, and overall premature death[104,105]. Higher serum concentrations of choline
have been linked with prostate cancer development and progression[106-108], and consuming as little as one egg
every 3 days has shown to increase the risk prostate cancer mortality by about 81%.
Diet vs. exercise for prostate cancer
In 2005, Dean Ornish, a researcher well known for his studies showing that plant based diets can reverse
atherosclerotic plaque lesions in heart disease, began studying the 2nd leading cause of death, cancer. Ornish
created a series of experiments where he placed subjects on dierent diets, dripped their blood on cancer cells
in vitro, and observed their growth rates[10 9]. Results showed that those randomized to the plant nutrition
group has blood samples much less hospitable to cancer growth, fighting cancer 8 times better than the
standard American diet. ose eating the standard American diets blood suppressed cancer cell growth by
about 9%, vs. 70% in men who were eating plant based for a year[10 9]. One limitation in interpreting these
results is that most lifestyle interventional studies involve changing not only diet, but exercise regimens
as well. A University of California at Los Angeles team thus devised a research study comparing among
3 groups of men in order to isolate the eects of diet. One group ate plant based and exercised, one just
exercised while eating standard American diet, and one was a control of sedentary individuals eating the
standard American diet. In the diet and exercise group, those subjects had been following a plant based diet
for 14 years in addition to regular moderate exercise, whereas the exercise group consisted of those with
a 15-year history of daily strenuous exercise for at least an hour per day. After dripping the blood of the
participants on prostate cancer cells in vitro, it was found that the control groups blood killed 1%-2% of cancer
cells, the exercise group killed 2000% more than controls, and the plant eaters killed 4000% more. erefore,
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results showed that exercise does play a part in cancer protection and an overall healthy lifestyle, but it cannot
substitute for eating a healthy plant-based diet, and does not negate the eects of eating animal products.
Prostate cancer regression via nutritional intervention
In 2005 Dr. Dean Ornish studied 93 men with prostate cancer who chose not to undergo conventional
therapy in order to test the effects of intensive lifestyle changes on disease progression. Men were
randomized into the control group who weren’t given additional diet/lifestyle instructions outside of what
their primary care physicians may have told them, and the experimental group were prescribed a vegan diet
along with walking 30 min a day, 6 days a week[108 ]. Prostate cancer progression was tracked using prostate
specic antigen (PSA) levels. At 1-year follow-up, control group PSA levels rose on average of 6%, whereas
the plant based groups dropped by 4%, suggesting tumor shrinkage vs. growth. Additionally, biopsies taken
pre and post dietary intervention demonstrated that the altered expression of over 500 genes, showing that
changing ones’ diet and lifestyle can have signicant eects on gene expression. At 2-year follow-up, it was
found that about 10% of control group patients had to undergo radical prostatectomy due to tumor growth,
whereas none of the plant-based group ended up needing surgery for cancer progression. Another study
in 2012 at the University of Massachusetts aimed to determine if simply reducing the ratio of animal to plant
proteins would be enough to halt or reverse prostate cancer progression. Subjects were randomized into
2 groups, one getting instructional classes on plant-based eating and achieving a 1:1 animal to plant protein
ratio, and the other getting no dietary instructions, remaining at about a 3:1 ratio. PSA levels were analyzed,
and doubling times in the plant group were lengthened from an average of 21 months to 58 months. is
sounds like a very positive result, and it is, however the same eects of complete reversal that were found in
previous studies of fully vegan diets, were not found in this case. erefore, these results indicate that the
safest ratio of animal to plant proteins may be 0:1.
In looking at specic plant foods that may oer particular benets and protection against prostate cancer,
soy and flaxseeds are ones to note. Just as in breast cancer, prostate cancer incidence is found to be
signicantly less in Asian men who tend to consume more soy products and thus more isoavones than the
typical Western/American diet[114 ]. Japanese and Chinese men have found to have 30 and 120 times less rates
of prostate cancer than African American men respectively, partly due to higher fat intake in Western diets,
but also because of soy consumption. In addition to isoavones, lignans are relevant in prostate cancer as
well, and research has shown that the levels of lignans in the prostate uid of men with low rates of cancer
are higher than those with higher rates of cancer.
In 2001, a pilot study was conducted to determine if pre-operative consumption of flaxseed would alter
PSA, hormone levels, and histopathological findings. For one month prior to prostatectomy, patients
consumed 3 tablespoons of axseed per day. Post-operative tumor analysis then showed decreased rates of
cell proliferation, and increased cancer cell clearance. In addition to helping reverse existing prostate cancer,
axseeds have also shown to prevent it from developing. In a study of men with biopsy conrmed prostatic
intraepithelial neoplasia, a precancerous prostatic lesion, 15 subjects were asked to consume 3 tablespoons
of axseed per day for the subsequent 6 months until their next scheduled biopsy. e men’s PSA levels and
cell-proliferation rates decreased, and 2 of the 15 men saw such a drastic decrease in their PSA levels that
they did not require a 2nd biopsy[116-118]. e evidence suggests that axseed is a low-cost, safe nutritious food
with potential to reduce the risk of prostate cancer and improve survival.
PLANT-BASED NUTRITION AND COLORECTAL CANCER
Colorectal cancer (CRC) is the third most common cancer in men and the second most common cancer
in women worldwide with more than half of cases occurring in developed countries. Diet and obesity have
been shown to play major roles in modulating the risk for colon cancer. Fortunately, diet is a modiable
factor and a change can be made from a disease promoting pattern to a protective pattern. While certain
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individual foods have been implicated as either increasing or decreasing colon cancer risk, the overall
pattern of food intake may offer the greatest influence on the development of disease. Numerous studies
have shown that diets high in unrefined plant foods such as fruits, vegetables and whole grains provide
protection against colon cancer while diets high in meat and saturated fat increase the risk of colon cancer.
us, implicating vegan and vegetarian diets as potentially benecial in preventing CRC. In the Adventist
Health studies where a large prospective cohort of nearly 80,000 subjects was followed, vegetarian diets
were associated with an overall lower incidence of CRC compared to non-vegetarians[119, 12 0]. e protective
eect of plant-based diets may be due in part to exclusion of meat which contains harmful substances such
as saturated fats and carcinogens formed during the cooking or processing of meats. Additional protection
by plant-based diets can be offered by inclusion of several beneficial plant constituents including fiber
and micronutrients. Plant-based diets may also aid in weight loss or weight maintenance which may oer
protection against the increased CRC risk associated with obesity. Responsible for the protective eect of
vegan and vegetarian diets are plant-based foods including vegetables, fruits, whole grains, legumes, nuts
and seeds[121-124]. Intake of fruits and vegetables and high fiber intake, particularly from vegetables and
whole grains, has been associated with reduced risk of CRC in systematic meta-analyses and epidemiologic
studies[125 -1 30 ]. Fiber may help protect against CRC by reducing fecal bile acid concentrations and by being
paired with micronutrients and minerals such as magnesium. A large meta-analysis including nearly 340,000
subjects found a decrease of roughly 10% in CRC risk between those consuming the most magnesium
and those consuming the least magnesium[131,132]. This protective effect may be mediated by the ability of
magnesium to promote DNA repair and stability of the genome. Epidemiological observations have also
demonstrated a decrease in the incidence of cancer when consuming a diet of plant-based foods that is rich
in phytochemicals. Phytochemicals are plant metabolites that can exert a chemopreventive eect through
their antioxidant properties that act to lower oxidative stress-induced DNA damage, thus protecting cells
from mutations that trigger carcinogenesis. This may contribute to the protective effect of plant-based
diets against colon cancer. Some phytochemicals that may offer protection include curcumin (turmeric),
epigallocatechin gallate (green tea), resveratrol (grapes), phenethyl isothiocyanate, sulforaphane (cruciferous
vegetables), hesperidin, quercetin and 2’-hydroxyavanone (citrus fruits). Other protective elements in
a cancer-preventive diet include selenium, probiotics, folic acid, vitamin B12, vitamin D, chlorophyll and
antioxidants such as carotenoids[134 ].
e harmful eects of meat were perhaps rst noted in an epidemiologic study supplying evidence about the
association between red meat and CRC risk. A demonstration of correlation between per capita meat intake
and incidence of colon cancer was shown in women from 23 countries in 1975. A strong association
between red and processed meats and colon cancer has since been shown in numerous studies and large
meta-analyses[136-139]. Several compounds in meat are thought to be responsible for this association. ese
compounds include polycyclic aromatic hydrocarbons, nitrosamines, HCAs formed during cooking, and
heme iron causing pro-oxidant effects[140 -14 2]. Other factors associated with increased CRC risk are foods
containing high amounts of saturated fats and cholesterol as well as high serum levels of cholesterol,
oxidized low density lipoprotein and triglycerides[143 -145]. In those individuals with an existing diagnosis of
colon cancer, western diets have been implicated with lower survival rates . In contrast, a diet lower in red
and processed meats and higher in fruits, vegetables and whole grains combined with exercise and healthy
body weight has been shown to prolong overall and disease-free survival rates .
PLANT-BASED NUTRITION AND OTHER CANCERS
Plant-based diets have also been shown to oer protection against a myriad of other GI and non-GI cancers.
A systematic review and meta-analysis found a two-fold difference in gastric cancer risk among those
eating a healthy diet with high fruit and vegetable content to those eating a Western diet high in meat,
fats and starches. Especially processed and red meat intake has been associated with increased gastric
cancer risk[148 ] which may be partially mediated by the food preservative nitrites used in processed meats.
Madigan et al. J Unexplored Med Data 2018;3:9 I http://dx.doi.org/ 10.20517/2572-8180.2017.05 Page 9 of 16
In contrast, plant sources of nitrates are not associated with increased gastric cancer risk . Likewise,
pancreatic cancer risk increases with higher intakes of red meats and animal fats while fruits, vegetables
and whole grains appear to lower the risk[150-152]. A review of dietary cervical cancer prevention strategies
also found a high intake of fruits and vegetables to be protective against cervical intraepithelial neoplasia.
Higher serum vitamin, mineral and antioxidant concentrations were found in association with reduced risk
of high-grade cervical intraepithelial neoplasia . In endometrial cancer an increased risk has been noted
in those consuming a Western diet high in animal products and rened carbohydrates[15 4] while a diet high
in plant foods appears protective. In another study, increased saturated fat intake in those with higher
circulating estrogen was found to be the main contributing factor associated with endometrial cancer while
consumption of fruits and vegetables was inversely associated with endometrial cancer risk[15 6]. Similarly,
highest fat intake from animal products was tied to 30% increase in ovarian cancer risk when compared to
those eating the lowest amount of animal fat. Dietary patterns have also been shown to inuence lung
cancer risk. Again, diets high in meat were found to increase lung cancer risk by 35% and two recent
meta-analyses concluded that risk for lung cancer was greatly reduced in those consuming the most fruits
and vegetables compared to those consuming the least[159,160]. The harmful effects of Western diets high
in meat are likely inf luenced both by inclusion of damaging compounds in meat as well as exclusion of
protective components in plant foods.
Diet is one of the main causes of premature death and disability in developed countries and contributes
to the burden of cancers commonly encountered in Western society. Due to the strong influence of diet
on cancer incidence and progression as well as the large financial burden imposed by current treatment
regimens, prevention through adherence to a mainly plant-based diet presents an attractive means of
combating the problem. Though there remain some misconceptions about vegan diets, particularly
concerning iron and B12, e Academy of Nutrition and Dietetics’ ocial position on plant based diets states
that “appropriately planned vegetarian, including vegan, diets are healthful, nutritionally adequate, and may
provide health benets for the prevention and treatment of certain diseases including ischemic heart disease,
type 2 diabetes, hypertension, certain types of cancer, and obesity”. erefore, concerns about nutritional
inadequacy of vegan diets are unwarranted when diets are appropriately constructed.
Plant-based diets have also shown to be healthy and beneficial for children. The authors did not come
across any studies regarding nutritional interventions for cancers in children specifically, however plant-
based nutrition is associated with improved general health and prevention of chronic diseases in children as
well as adults. For example, the consumption of animal-sourced protein at one year of age has shown to be
positively correlated with increased body mass index and body fat by 6-7 years of age[162-164]. Excess weight
in childhood is linked to many chronic disease conditions including insulin resistance, type 2 diabetes,
hypertension, and cardiovascular disease . Since pre-cancerous changes and development of risk factors
can begin years before clinical cancer presents itself, even as early as in utero, and considering that habits
developed in childhood oen persist into adulthood, it is benecial to develop healthy nutritional patterns at
the start of life to help promote longevity and a disease free existence.
As reviewed in this article, adoption of a plant-based diet provides robust benets against a multitude of
cancers while presenting virtually no threat of unwanted side-effects. A well-planned plant-based diet
is a simple and cost-effective intervention that can be used alone to prevent disease or in adjunct with
conventional treatment when disease is already present. Besides oering protection against cancers, a plant-
based diet has also been shown to be protective against other Western chronic diseases including diabetes,
heart disease, and obesity. e current inadequacy in nutrition education and knowledge among physicians
remains a barrier for more widespread prescription of diet change for cancer prevention that should be
addressed starting early in medical education. With the unsustainable nature of current cancer treatment
Page 10 of 16 Madigan et al. J Unexplored Med Data 2018;3:9 I http://dx.doi.org/ 10.20517/2572-8180.2017.05
regimens, focus on prevention, especially through diet and lifestyle changes, presents an important
paradigm shi with the potential to make a marked impact on the burden of disease.
Conception and design, administrative support: Madigan, M
Provision of study materials or patients, collection and assembly of data, data analysis and interpretation,
manuscript writing, nal approval of manuscript: Madigan M, Karhu E
Availability of data and materials
Financial support and sponsorship
Conflicts of interest
All authors declared that there are no conicts of interest.
Ethical approval and consent to participate
Consent for publication
© e Author(s) 2018.
1. Lenders C, Gorman K, Milch H, Decker A, Harvey N, et al. A novel nutrition medicine education model: the Boston University
experience. Adv Nutr 2013;4:1-7.
2. Murray CJ, Atkinson C, Bhalla K, Birbeck G, Burstein R, et al. The state of US health, 1990-2010: burden of diseases, injuries, and risk
factors. JAMA 2013;310:591-608.
3. McCarty MF. Mortality from Western cancers rose dramatically among African-Americans during the 20th century: are dietary animal
products to blame? Medical hypotheses 2001;57:169-74.
4. McCarty MF. Insulin and IGF-I as determinants of low “Western” cancer rates in the rural third world. Int J Epidemiol 2004;33:908-10.
5. Bouvard V, Loomis D, Guyton KZ, Grosse Y, Ghissassi FE, et al. Carcinogenicity of consumption of red and processed meat. Lancet
6. Inoue-Choi M, Sinha R, Gierach GL, Ward MH. Red and processed meat, nitrite, and heme iron intakes and postmenopausal breast
cancer risk in the NIH-AARP diet and health study. Int J Cancer 2016;138:1609-18.
7. Larsson SC, Wolk A. Meat consumption and risk of colorectal cancer: a meta-analysis of prospective studies. Int J Cancer
8. NoratT,BinghamS, FerrariP,SlimaniN,Jenab M,etal.Meat,sh, andcolorectalcancerrisk:the Europeanprospectiveinvestigation
into cancer and nutrition. J Natl Cancer Inst 2005;97:906-16.
9. Rohrmann S, Overvad K, Bueno-de-Mesquita HB, Jakobsen MU, Egeberg R, et al. Meat consumption and mortality--results from the
European prospective investigation into cancer and nutrition. BMC Med 2013;11:63.
10. Greger M, Stone G. How not to die. 1th ed. New York: Macmillan Audio; 2015.
11. DinuM,AbbateR,GensiniGF,CasiniA,SoF.Vegetarian,vegandietsand multiplehealth outcomes:asystematicreviewwithmeta-
analysis of observational studies. Crit Rev Food Sci Nutr 2017;57:3640-9.
12. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, et al. Cancer incidence and mortality worldwide: sources, methods and major
patterns in GLOBOCAN 2012. Int J Cancer 2015;136:E359-86.
29 Oct 2018]
Madigan et al. J Unexplored Med Data 2018;3:9 I http://dx.doi.org/ 10.20517/2572-8180.2017.05 Page 11 of 16
14. Greger M, Stone G. How not to die. 1th ed. New York: Macmillan Audio; 2015. p. 178.
16. Friberg S, Mattson S. On the growth rates of human malignant tumors: implications for medical decision making. J Surg Oncol
17. Philippe E, Le Gal Y. Growth of seventy-eight recurrent mammary cancers. Quantitative study. Cancer 1968;21:461-7.
18. Kuroishi T, Tominaga S, Morimoto T, Tashiro H, Itoh S, et al. Tumor growth rate and prognosis of breast cancer mainly detected by mass
screening. Jpn J Cancer Res 1990;81:454-62.
19. Nielsen M, Thomsen JL, Primdahl S, Dyreborg U, Andersen JA. Breast cancer and atypia among young and middle-aged women: a study
of 110 medicolegal autopsies. Br J Cancer 1987;56:814-9.
20. Sanders ME, Schuyler PA, Dupont WD, Page DL. The natural history of low-grade ductal carcinoma in situ of the breast in women
treated by biopsy only revealed over 30 years of long-term follow-up. Cancer 2005;103:2481-4.
21. Soto AM, Brisken C, Schaeberle C, Sonnenschein C. Does cancer start in the womb? Altered mammary gland development and
predisposition to breast cancer due to in utero exposure to endocrine disruptors. J Mammary Gland Biol Neoplasia 2013;18:199-208.
22. AmericanInstituteforCancerResearch. Recommendations for cancerprevention.Availablefrom: http://www.aicr.org/reduce-your-
23. HastertTA,BeresfordSA,Patterson RE,KristalAR,WhiteE.AdherencetoWCRF/AICRcancerpreventionrecommendationsand risk
of postmenopausal breast cancer. Cancer Epidemiol Biomarkers Prev 2013;22:1498-508.
24. BarnardRJ,GonzalezJH, LivaME,Ngo TH.Effectsofalow-fat, high-berdietandexerciseprogram onbreastcancer riskfactorsin
vivo and tumor cell growth and apoptosis in vitro. Nutr Cancer 2006;55:28-34.
25. Ngo TH, Barnard RJ, Tymchuk CN, Cohen P, Aronson WJ. Effect of diet and exercise on serum insulin, IGH-1, and IGFBP-1 levels and
growth of LNCaP cells in vitro (United States). Cancer Causes Control 2002;13:929-35.
26. Allen NE, Appleby PN, Davey GK, Kaaks R, Rinaldi S, et al. The associations of diet with serum insulin-like growth factor I and its main
binding proteins in 292 women meat-eaters, vegetarians, and vegans. Cancer Epidemiol Biomarkers Prev 2002;11:1441-8.
27. Rowlands MA, Gunnell D, Harris R, Vatten LJ, Holly JM, et al. Circulating insulin-like growth factor peptides and prostate cancer risk: a
systemic review and meta-analysis. Int J Cancer 2009;124:2416-29.
28. SolimanS,AronsonWJ, BarnardRJ.Analyzing serum-stimulatedprostatecancercell lines afterlow-fat,high-berdietand exercise
intervention. Evid Based Complement Alternat Med 2011;2011:529053.
29. Allen NE, Appleby PN, Davey GK, Key TJ. Hormones and diet: low insulin-like growth factor-I but normal bioavailable androgens in
vegan men. Br J Cancer 2000;83:95-7.
30. Widmark EMP. Presence of cancer-producing substances in roasted food. Nature 1939;143:984.
31. NationalCancerInstitute.Chemicalsinmeat cooked athightemperaturesandcancer risk.Availablefrom:http://www.cancer.gov/
32. Thiébaud HP, Knize MG, Kuzmicky PA, Hsieh DP, Felton JS. Airborne mutagens produced by frying beef, pork and a soy-based food.
Food Chem Toxicol 1955;33:821-8.
33. Zheng W, Lee SA. Well-done meat intake, heterocyclic amine exposure, and cancer risk. Nutr Cancer 2009;61:437-46.
34. Zaidi R, Kumar S, Rawat PR. Rapid detection and quantification of dietary mutagens in food using mass spectrometry and ultra
performance liquid chromography. Food Chem 2012;135:2897-903.
35. Shaughnessy DT, Gangarosa LM, Schliebe B, Umbach DM, Xu Z, et al. Inhibition of fried meat-induced colorectal DNA damage and
altered systemic genotoxicity in humans by crucifera, chlorophyllin, and yogurt. PLoS One 2011;6:e18707.
36. Steck SE, Gaudet MM, Eng SM, Britton JA, Teitelbaum SL, et al. Cooked meat and risk of breast cancer--lifetime versus recent dietary
intake. Epidemiology 2007;18:373-82.
37. Zheng W, Gustafson DR, Sinha R, Cerhan JR, Moore D, et al. Well-done meat intake and the risk of breast cancer. J Natl Cancer Inst
38. Rohrmann S, Lukas Jung SU, Linseisen J, Pfau W. Dietary intake of meat and meat-derived heterocyclic aromatic amines and their
correlation with DNA adducts in female breast tissue. Mutagenesis 2009;24:127-32.
39. LauberSN,AliS,Gooderham NJ.Thecookedfood derived carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridineisapotent
40. DeBruinLS, MartosPA,JosephyPD. Detection ofPhIP(2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine)inthemilk of healthy
women. Chem Res Toxicol 2001;14:1523-8.
41. Grose KR, Grant JL, Bjeldanes LF, Andresen BD, Healy SK, et al. Isolation of the carcinogen IQ from fried egg patties. J Agric Food
42. Maunsell E, Drolet M, Brisson J, Robert J, Deschênes L. Dietary change after breast cancer: extent, predictors, and relation with
psychological distress. J Clin Oncol 2002;20:1017-25.
43. Pierce JP, Stefanick ML, Flatt SW, Natarajan L, Sternfeld B, et al. Greater survival after breast cancer in physically active women with
high vegetable-fruit intake regardless of obesity. J Clin Oncol 2007;25:2345-51.
status. Eur J Nutr 2013;52:217-23.
45. Howe GR, Hirohata T, Hislop TG, Iscovich JM, Yuan JM, et al. Dietary factors and risk of breast cancer: combined analysis of 12 case-
control studies. J Natl Cancer Inst 1990;82:561-9.
analysis of prospective studies. Ann Oncol 2012;23:1394-402.
Page 12 of 16 Madigan et al. J Unexplored Med Data 2018;3:9 I http://dx.doi.org/ 10.20517/2572-8180.2017.05
realistic solutions with a focus on grain-based foods. J Nutr 2012;142:1390S-401S.
49. RizzoNS, Jaceldo-Siegl K,SabateJ,Fraser GE. Nutrient prolesofvegetarianand nonvegetarian dietary patterns.JAcadNutrDiet
50. Dewell A, Weidner G, Sumner MD, Chi CS, Ornish D. A very-low-fat vegan diet increases intake of protective dietary factors and
decreases intake of pathogenic dietary factors. J Am Diet Assoc 2008;108:347-56.
51. Greger M, Stone G. How not to die. 1th ed. New York: Macmillan Audio; 2015. p. 191.
52. Murray S, Lake BG, Gray S, Edwards AJ, Springall C, et al. Effect of cruciferous vegetable consumption on heterocyclic aromatic amine
metabolism in man. Carcinogenesis 2001;22:1413-20.
53. Thiébaud HP, Knize MG, Kuzmicky PA, Hsieh DP, Felton JS. Airborne mutagens produced by frying beef, pork, and soy-based food.
Food Chem Toxicol 1995;33:821-8.
54. GoyalA,SharmaV,UpadhyayN,GillS, Sihag M. Flaxandaxseedoil: an ancient medicine&modernfunctionalfood. J Food Sci
55. SmedsAI,EklundPC,SjöholmRE,WillförSM, NishibeS,etal.Quanticationofabroadspectrumoflignansincereals,oilseeds,and
nuts. J Agric Food Chem 2007;55:1337-46.
56. Rosolowich V, Saettler E, Szuck B; Breast Disease Committee. Mastalgia. J Obstet Gynecol Can 2006;28:49-57.
58. Knekt P, Adlercreutz H, Rissanen H, Aromaa A, Teppo L, et al. Does antibacterial treatment for urinary tract infection contribute to the
risk of breast cancer? Br J Cancer 2000;82:1107-10.
59. Abarzua S, Serikawa T, Szewczyk M, Richter DU, Piechulla B, et al. Antiproliferative activity of lignans against the breast carcinoma cell
lines MCF 7 and BT 20. Arch Gynecol Obstet 2012;285:1145-51.
60. Fabian CJ, Kimler BF, Zalle CM, Klemp JR, Petroff BK, et al. Reduction in Ki-67 in benign breast tissue of high-risk women with the
lignan secoisolariciresinil diglycoside (SDG). Cancer Prev Res (Phila) 2010;3:1342-50.
61. Buck K, Vrieling A, Zaineddin AK, Becker S, Hüsing A, et al. Serum enterolactone and prognosis of postmenopausal breast cancer. J Clin
62. Guglielmini P, Rubagotti A, Boccardo F. Serum enterolactone levels and mortality outcome in women with early breast cancer: a
retrospective cohort study. Breast Cancer Res Treat 2012;132:661-8.
63. McCann SE, Thompson LU, Nie J, Dorn J, Trevisan M, et al. Dietary Lignan intakes in relation to survival among women with breast
cancer: the Western New York exposures and breast cancer (WEB) study. Breast Cancer Res Treat 2010;122:229-35.
64. ÅbergUW,SaarinenN,AbrahamssonA, NurmiT,EngblomS,etal. Tamoxifenand axseedalterangiogenesisregulators in normal
human breast tissue in vivo. PLoS One 2011;6:e25720.
65. ThompsonLU,ChenJM, LiT,Strasser-WeipplK,GossPE. Dietaryaxseedalters tumorbiologicalmarkers inpostmenopausalbreast
cancer. Clin Cancer Res 2005;11:3828-35.
66. Parkin DM, Fernández LM. Use of statistics to assess the global burden of breast cancer. Breast J 2006;12:S70-80.
67. Wu AH, Butler LM. Green tea and breast cancer. Mol Nutr Food Res 2011;55:921-30.
68. Singh M, Vijay B, Kamal S, Wakchaure GC. Production and marketing of mushrooms: global and national scenario. In: Singh M, Vijay
B, Kamal S, Wakchaure GC, editors. Mushrooms: cultivation, marketing and consumption. India: Directorate of Mushroom Research;
2014. pp. 15-22.
69. Greger M, Stone G. How not to die. 1th ed. New York: Macmillan Audio; 2015. pp. 196-7.
70. Korde LA, Wu AH, Fears T, Nomura AM, West DW, et al. Childhood soy intake and breast cancer risk in Asian American women. Cancer
Epidemiol Biomarkers Prev 2009;18:1050-9.
71. Greger M, Stone G. How not to die. 1th ed. New York: Macmillan Audio; 2015. p. 195.
72. Mueller SO, Simon S, Chae K, Metzler M, Korach KS. Phytoestrogens and their human metabolites show distinct agonistic and
antagonistic properties on estrogen receptor alpha (ERalpha) and ERbeta in human cells. Toxicol Sci 2004;80:14-25.
73. Oseni T, Patel R, Pyle J, Jordan VC. Selective estrogen receptor modulators and phytoestrogens. Planta Med 2008;74:1656-65.
74. Nagata C, Mizoue T, Tanaka K, Tsuji I, Tamakoshi A, et al. Soy intake and breast cancer risk: an evaluation based on a systemic review of
epidemiologic evidence among the Japanese population. Jpn J Clin Oncol 2014;44:282-95.
75. ChenMN, Lin CC,LiuCF.Efcacyof phytoestrogens formenopausalsymptoms:a meta-analysis andsystematicreview.Climacteric
76. Chi F, Wu R, Zeng YC, Xing R, Liu Y, et al. Post-diagnosis soy food intake and breast cancer survival: a meta-analysis of cohort studies.
Asian Pac J Cancer Prev 2013;14:2407-12.
77. KangHB,ZhangYF,YangJD,LuKL.Studyonsoyisoavoneconsumptionand riskofbreastcancerandsurvival.AsianPacJCancer
78. USDANationalAgriculturalLibrary.USDAdatabase fortheisoavonecontent of selectedfoods,release 2.0.Availablefrom:https://
79. Nechuta SJ, Caan BJ, Chen WY, Lu W, Chen Z, et al. Soy food intake after diagnosis of breast cancer and survival: an in-depth analysis
of combined evidence from cohort studies of US and Chinese women. Am J Clin Nutr 2012;96:123-32.
80. Bosviel R, Dumollard E, Déchelotte P, Bignon YJ, Bernard-Gallon D. Can soy phytoestrogens decrease DNA methylation in BRCA1 and
BRCA2 oncosuppressor genes in breast cancer? OMICS 2012;16:235-44.
81. Colditz GA, Willett WC, Hunter DJ, Stampfer MJ, Manson JE, et al. Family history, age, and risk of breast cancer. Prospective data from
the nurses’ health study. JAMA 1993;270:338-43.
82. Bal A, Verma S, Joshi K, Singla A, Thakur R, et al. BRCA1-methylated sporadic breast cancers are BRCA-like in showing a basal
phenotype and absence of ER expression. Virchows Arch 2012;461:305-12.
Madigan et al. J Unexplored Med Data 2018;3:9 I http://dx.doi.org/ 10.20517/2572-8180.2017.05 Page 13 of 16
83. Magee PJ, Rowland I. Soy products in the management of breast cancer. Curr Opin Clin Nutr Metab Care 2012;15:586-91.
on 30 Oct 2018]
85. Jahn JL, Giovannucci EL, Stampfer MJ. The high prevalence of undiagnosed prostate cancer at autopsy: implications for epidemiology
86. Greger M, Stone G. How not to die. 1th ed. New York: Macmillan Audio; 2015. p. 213.
87. Maruyama K, Oshima T, Ohyama K. Exposure to exogenous estrogen through intake of commercial milk produced from pregnant cows.
Pediatr Int 2010;52:33-8.
88. Danby FW. Acne and milk, the diet myth, and beyond. J Am Acad Dermatol 2005;52:360-2.
89. Afeiche M, Williams PL, Mendiola J, Gaskins AJ, Jørgensen N, et al. Dairy food intake in relation to semen quality and reproductive
hormone levels among physically active young men. Hum Reprod 2013;28:2265-75.
90. Steinman G. Mechanisms of twinning: VII. Effect of diet and heredity on the human twinning rate. J Reprod Med 2006;51:405-10.
91. Melnik BC, John SM, Schmitz G. Milk is not just food but most likely a genetic transfection system activating mTORC1 signaling for
postnatal growth. Nutr J 2013;12:103.
92. Ludwig DS, Willett WC. Three daily servings of reduced-fat milk: an evidence-based recommendation? JAMA Pediaatr 2013;167:788-9.
93. Tate PL, Bibb R, Larcom LL. Milk stimulated growth of prostate cancer cells in culture. Nutr Cancr 2011;63:1361-6.
94. Ganmaa D, Li XM, Qin LQ, Wang PY, Takeda M, et al. The experience of Japan as a clue to the etiology of testicular and prostatic
cancers. Med Hypotheses 2003;60:724-30.
95. Ganmaa D, Li XM, Wang J, Qin LQ, Wang PY, et al. Incidence and mortality of testicular and prostatic cancers in relation to world
dietary practices. Int J Cancer 2002;98:262-7.
96. Qin LQ, Xu JY, Wang PY, Kaneko T, Hoshi K, et al. Milk consumption is a risk factor for prostate cancer: meta-analysis of case-control
studies. Nutr Cancer 2004;48:22-7.
97. 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.
98. Aune D, Navarro Rosenblatt DA, Chan DS, Vieira AR, Vieira R, et al. Dairy products, calcium, and prostate cancer risk: a systematic
review and meta-analysis of cohort studies. Am J Clin Nutr 2015;101:87-117.
99. Epstein SS. Unlabeled milk from cows treated with biosynthetic growth hormones: a case of regulatory abdication. Int J Health Serv
100. Cui X, Wang L, Zuo P, Han Z, Fang Z, et al. D-galactose-caused life shortening in drosophilia melanogaster and musca domestica is
associated with oxidative stress. Biogerontology 2004;5:317-25.
101. Cui X, Zuo P, Zhang Q, Li X, Hu Y, et al. Chronic systemic D-galactose exposure induces memory loss, neurodegeneration, and oxidative
damage in mice: protective effects of R-alpha-lipoic acid. J Neurosci Res 2006;84:647-54.
102. Michaëlsson K, Wolk A, Langenskiöld S, Basu S, Warensjö Lemming E, et al. Milk intake and risk of mortality and fractures in women
and men: cohort studies. BMJ 2014;349:g6015.
103. Schooling CM. Milk and mortality. BMJ 2014;349:g6205.
progression. Am J Clin Nutr 2010;91:712-21.
105. Tang WH, Wang Z, Levison BS, Koeth RA, Britt EB, et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular
risk. N Eng J Med 2013;368:1575-84.
106. Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes
atherosclerosis. Nat Med 2013;19:576-85.
107. Johansson M, Van Guelpen B, Vollset SE, Hultdin J, Bergh A, et al. One-carbon metabolism and prostate cancer risk: prospective
investigation of seven circulating B vitamins and metabolites. Cancer Epidemiol Biomarkers Prev 2009;18:1538-43.
108. RichmanEL,KeneldSA, StampferMJ,GiovannucciEL,Chan JM.Egg,redmeat,and poultryintakeandriskof lethalprostatecancer
109. Ornish D, Weidner G, Fair WR, Marlin R, Pettengill EB, et al. Intensive lifestyle changes may affect the progression of prostate cancer. J
110. BarnardRJ,Gonzalez JH,Liva ME,NgoTH.Effects ofalow-fat, high-berdietand exerciseprogramon breastcancerrisk factorsin
vivo and tumor cell growth and apoptosis in vitro. Nutr Cancer 2006;55:28-34.
111. BarnardRJ, NgoTH,LeungPS,AronsonWJ, GoldingLA.Alow-fatdiet and/orstrenuous exercisealtersthe IGFaxisinvivoand
reduces prostate tumor cell growth in vitro. Prostate 2003;56:201-6.
112. Ornish D, Magbanua MJ, Weidner G, Weinberg V, Kemp C, et al. Changes in prostate gene expression in men undergoing an intensive
nutrition and lifestyle intervention. Proc Natl Acad Sci U S A 2008;105:8369-74.
113. Frattaroli J, Weidner G, Dnistrian AM, Kemp C, Daubenmier JJ, et al. Clinical events in prostate cancer lifestyle trial: results from two
years of follow-up. Urology 2008;72:1319-23.
114. Carmody JF, Olendzki BC, Merriam PA, Liu Q, Qiao Y, et al. A novel measure of dietary change in a prostate cancer dietary program
incorporating mindfulness training. J Acad Nutr Diet 2012;112:1822-7.
115. vanDie MD,BoneKM, WilliamsSG, PirottaMV.Soy andsoy isoavonesinprostate cancer:a systemicreviewand meta-analysisof
randomized controlled trials. BJU Int 2014;113:E119-30.
116. MortonMS, ChanPS,Cheng C,Blacklock N,Matos-FerreiraA,et al.Lignans andisoavanoidsin plasmaand prostaticuidin men:
samples from Portugal, Hong Kong, and the United Kingdom. Prostate 1997;32:122-8.
117. Demark-Wahnefried W, PriceDT,Polascik TJ,Robertson CN,AndersonEE, etal. Pilotstudy ofdietaryfat restrictionand axseed
supplementationin men withprostatecancerbefore surgery:exploringthe effects onhormonallevels,prostate-specic antigen,and
histopathological features. Urology 2001;58:47-52.
Page 14 of 16 Madigan et al. J Unexplored Med Data 2018;3:9 I http://dx.doi.org/ 10.20517/2572-8180.2017.05
118. Demark-Wahnefried W, RobertsonCN, Walther PJ,Polascik TJ,Paulson DF, etal. Pilotstudy toexploreeffects oflow-fat, axseed-
119. Demark-Wahnefried W, Polascik TJ, George SL, Switzer BR, Madden JF, et al. Flaxseed supplementation (not dietary fat restriction)
reduces prostate cancer proliferation rates in men presurgery. Cancer Epidemiol Biomarkers Prev 2008;17:3577-87.
120. Orlich MJ, Singh PN, Sabaté J, Fan J, Sveen L, et al. Vegetarian dietary patterns and the risk of colorectal cancers. JAMA Intern Med
121. Tantamango-Bartley Y, Jaceldo-Siegl K, Fan J, Fraser G. Vegetarian diets and the incidence of cancer in a low-risk population. Cancer
Epidemiol Biomarkers Prev 2013;22:286-94.
122. Fraser GE. Associations between diet and cancer, ischemic heart disease, and all-cause mortality in non-Hispanic white California
seventh-day adventists. Am J Clin Nutr 1999;70:532s-8s.
123. Tantamango YM, Knutsen SF, Beeson WL, Fraser G, Sabate J. Foods and food groups associated with the incidence of colorectal polyps:
the Adventist Health Study. Nutr Cancer 2011;63:565-72.
124. Wu L, Wang Z, Zhu J, Murad AL, Prokop LJ, et al. Nut consumption and risk of cancer and type 2 diabetes: a systematic review and
meta-analysis. Nutr Rev 2015;73:409-25.
125. Zhu B, Sun Y, Qi L, Zhong R, Miao X. Dietary legume consumption reduces risk of colorectal cancer: evidence from a meta-analysis of
cohort studies. Sci Rep 2015;5:8797.
126. AuneD, ChanDS, LauR,VieiraR, GreenwoodDC,et al.Dietary bre,whole grains,andrisk ofcolorectal cancer:systematicreview
and dose-response meta-analysis of prospective studies. BMJ 2011;343:d6617.
127. Aune D, Lau R, Chan DS, Vieira R, Greenwood DC, et al. Nonlinear reduction in risk for colorectal cancer by fruit and vegetable intake
based on meta-analysis of prospective studies. Gastroenterology 2011;141:106-18.
128. Pan P, Yu J, Wang LS. Colon cancer: what we eat. Surg Oncol Clin N Am 2018;27:243-67.
129. Schwingshackl L, Schwedhelm C, Hoffmann G, Knüppel S, Laure Preterre A, et al. Food groups and risk of colorectal cancer. Int J
130. Tabung FK, Brown LS, Fung TT. Dietary patterns and colorectal cancer risk: a review of 17 years of evidence (2000-2016). Curr
Colorectal Cancer Rep 2017;13:440-54.
131. TantamangoYM,Knutsen SF,BeesonL, FraserG, Sabate J.Associationbetween dietaryber andincident cases ofcolon polyps:the
adventist health study. Gastrointest Cancer Res 2011;4:161-7.
132. Chen GC, Pang Z, Liu QF. Magnesium intake and risk of colorectal cancer: a meta-analysis of prospective studies. Eur J Clin Nutr
133. van den Brandt PA, Smits KM, Goldbohm RA, Weijenberg MP. Magnesium intake and colorectal cancer risk in the Netherlands cohort
study. Br J Cancer 2007;96:510-3.
134. Chikara S, Nagaprashantha LD, Singhal J, Horne D, Awasthi S, et al. Oxidative stress and dietary phytochemicals: role in cancer
chemoprevention and treatment. Cancer Lett 2018;413:122-34.
135. Divisi D, Di Tommaso S, Salvemini S, Garramone M, Crisci R. Diet and cancer. Acta Biomed 2006;77:118-23.
136. Armstrong B, Doll R. Environmental factors and cancer incidence and mortality in different countries, with special reference to dietary
practices. Int J Cancer 1975;15:617-31.
137. Bostick RM, Potter JD, Kushi LH, Sellers TA, Steinmetz KA, et al. Sugar, meat, and fat intake, and non-dietary risk factors for colon
cancer incidence in Iowa women (United States). Cancer Causes Control 1994;5:38-52.
138. GiovannucciE,RimmEB,StampferMJ,ColditzGA,AscherioA,etal.Intakeoffat,meat, andberinrelationtoriskofcoloncancerin
men. Cancer Res 1994;54:2390-7.
139. Goldbohm RA, van den Brandt PA, van ‘t Veer P, Brants HA, Dorant E, et al. A prospective cohort study on the relation between meat
consumption and the risk of colon cancer. Cancer Res 1994;54:718-23.
140. WillettWC, StampferMJ, ColditzGA, RosnerBA, SpeizerFE. Relationof meat, fat,and berintake tothe riskof coloncancer in a
prospective study among women. N Engl J Med 1990;323:1664-72.
141. Le Marchand L, Donlon T, Seifried A, Wilkens LR. Red meat intake, CYP2E1 genetic polymorphisms, and colorectal cancer risk. Cancer
Epidemiol Biomarkers Prev 2002;11:1019-24.
142. Lee DH, Anderson KE, Harnack LJ, Folsom AR, Jacobs DR Jr. Heme iron, zinc, alcohol consumption, and colon cancer: Iowa women’s
health study. J Natl Cancer Inst 2004;96:403-7.
143. Murtaugh MA, Ma KN, Sweeney C, Caan BJ, Slattery ML, et al. Meat consumption patterns and preparation, genetic variants of
metabolic enzymes, and their association with rectal cancer in men and women. J Nutr 2004;134:776-84.
144. Crespo-Sanjuán J, Calvo-Nieves MD, Aguirre-Gervás B, Herreros-Rodríguez J, Velayos-Jiménez B, et al. Early detection of high
oxidative activity in patients with adenomatous intestinal polyps and colorectal adenocarcinoma: myeloperoxidase and oxidized low-
density lipoprotein in serum as new markers of oxidative stress in colorectal cancer. Lab Med 2015;46:123-35.
145. Lee SA, Shu XO, Yang G, Li H, Gao YT, et al. Animal origin foods and colorectal cancer risk: a report from the Shanghai women’s health
study. Nutr Cancer 2009;61:194-205.
146. Yao X, Tian Z. Dyslipidemia and colorectal cancer risk: a meta-analysis of prospective studies. Cancer Causes Control 2015;26:257-68.
147. Van Blarigan EL, Meyerhardt JA. Role of physical activity and diet after colorectal cancer diagnosis. J Clin Oncol 2015;33:1825-34.
148. Bertuccio P, Rosato V, Andreano A, Ferraroni M, Decarli A, et al. Dietary patterns and gastric cancer risk: a systematic review and meta-
analysis. Ann Oncol 2013;24:1450-8.
149. Zhu H, Yang X, Zhang C, Zhu C, Tao G, et al. Red and processed meat intake is associated with higher gastric cancer risk: a meta-
analysis of epidemiological observational studies. PLoS One 2013;8:e70955.
150. Song P, Wu L, Guan W. Dietary nitrates, nitrites, and nitrosamines intake and the risk of gastric cancer: a meta-analysis. Nutrients
Madigan et al. J Unexplored Med Data 2018;3:9 I http://dx.doi.org/ 10.20517/2572-8180.2017.05 Page 15 of 16
151. Lei Q, Zheng H, Bi J, Wang X, Jiang T, et al. Whole grain intake reduces pancreatic cancer risk: a meta-analysis of observational studies.
Medicine (Baltimore) 2016;95:e2747.
152. Taunk P, Hecht E, Stolzenberg-Solomon R. Are meat and heme iron intake associated with pancreatic cancer? Results from the NIH-
AARP diet and health cohort. Int J Cancer 2016;138:2172-89.
153. Wu QJ, Wu L, Zheng LQ, Xu X, Ji C, et al. Consumption of fruit and vegetables reduces risk of pancreatic cancer: evidence from
epidemiological studies. Eur J Cancer Prev 2016;25:196-205.
154. Chih HJ, Lee AH, Colville L, Binns CW, Xu D. A review of dietary prevention of human papillomavirus-related infection of the cervix
and cervical intraepithelial neoplasia. Nutr Cancer 2013;65:317-28.
155. Si CJ, Shu L, Zheng PF, Zhang XY, Yu XL, et al. Dietary patterns and endometrial cancer: a meta-analysis. Eur J Cancer Prev
156. McCann SE, Freudenheim JL, Marshall JR, Brasure JR, Swanson MK, et al. Diet in the epidemiology of endometrial cancer in western
New York (United States). Cancer Causes Control 2000;11:965-74.
157. Littman AJ, Beresford SA, White E. The association of dietary fat and plant foods with endometrial cancer (United States). Cancer
Causes Control 2001;12:691-702.
158. Blank MM, Wentzensen N, Murphy MA, Hollenbeck A, Park Y. Dietary fat intake and risk of ovarian cancer in the NIH-AARP diet and
health study. Br J Cancer 2012;106:596-602.
159. Yang WS, Wong MY, Vogtmann E, Tang RQ, Xie L, et al. Meat consumption and risk of lung cancer: evidence from observational
studies. Ann Oncol 2012;23:3163-70.
160. Vieira AR, Abar L, Vingeliene S, Chan DS, Aune D, et al. Fruits, vegetables and lung cancer risk: a systematic review and meta-analysis.
Ann Oncol 2016;27:81-96.
161. Melina V, Craig W, Levin S. Position of the academy of nutrition and dietetics: vegetarian diets. J Acad Nutr Diet 2016;116:1970-80.
162. Voortman T, van den Hooven EH, Tielemans MJ, Hofman A, Kiefte-de Jong JC, et al. Protein intake in early childhood and
cardiometabolic health at school age: the generation R study. Eur J Nutr 2016;55:2117-27.
163. Voortman T, Braun KV, Kiefte-de Jong JC, Jaddoe VW, Franco OH, et al. Protein intake in early childhood and body composition at the
age of 6 years: the generation R study. Int J Obes (Lond) 2016;40:1018-25.
164. Günther AL, Remer T, Kroke A, Buyken AE. Early protein intake and later obesity risk: which protein sources at which time
points throughout infancy and childhood are important for body mass index and body fat percentage at 7 y of age? Am J Clin Nutr
165. Singh AS, Mulder C, Twisk JW, van Mechelen W, Chinapaw MJ. Tracking of childhood overweight into adulthood: a systematic review
of the literature. Obes Rev 2008;9:474-88.
Page 16 of 16 Madigan et al. J Unexplored Med Data 2018;3:9 I http://dx.doi.org/ 10.20517/2572-8180.2017.05