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Fig. 1 (a) Occurrence percentage of different types of cancer worldwide (Source: Global Cancer Observatory, https://gco.iarc.fr/). (b) Mortality
percentage of different types of cancer worldwide (Source: Global Cancer Observatory, https://gco.iarc.fr/)
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with the clinical interpretation of vast genomic data prevent
their widespread clinical application. The major obstacle to
precision oncology’s success is likely dealing with acquired
resistance and tumour heterogeneity. Contrarily, only a small
subset of patients benet from immune checkpoint inhibitors
(anti-cytotoxic T lymphocyte antigen-4 monoclonal antibodies and anti-programmed death cell protein-1/programmed
death cell ligand-1 [PD-1/L1]) in terms of long-term survival. There are currently no robustly validated predictive
markers that could aid in the identication of these subsets
and the improvement of treatment delivery and patient selection. A combination of drugs targeting various molecular
changes of cancer may be required to improve long-term survivance [3]. It is undeniably true that changes in lifestyle
have contributed to an elevation of metabolic diseases including, obesity, diabetes, metabolic disorders, and even cancer
[4, 5].
Only 5–10% of cancer occurrences can be traced to
genetic aws, whereas environmental and lifestyle factors
cause the other 90–95%. Infectious agents, including hepatitis viruses, human papillomavirus (HPV), and Helicobacter
pylori, as well as dietary variables, insufcient exercise, and
excessive body mass, are a few important causes and risk
factors for the cancers that are common in low- and middleincome countries (LMCs) [6]. Numerous factors have
smaller but still noticeable effects. The variables differ
according to how easily they can be changed [7, 8]. While
calcium, milk, bre, as well as whole grains decrease cancer
risks, foods like processed meat and red meat can raise
colorectal cancer threats. This can be elucidated by augmenting immunological receptivity, inammation, and excess
food intake, all of which are risk agents for colon cancer
development [9]. A diet high in vegetables, whole grains, and
fruits especially if it comprises plenty of soy products would
elevate the isoavones intake, thought to decrease cancer
risk [10]. The six basic properties of cancer are acquired by
human malignancies over the course of their multi-stage evolution. The distinctive traits act as a framework for organizing information in order to describe the complexity of the
neoplastic disease. One of them is maintaining proliferative
signalling, along with avoiding cell death inhibitors, replicative immortality, inducing angiogenesis, and promoting invasion and metastasis. These traits are characterized by genome
instability, which generates the genetic variation that expedites their acquisition and inammation, which supports
many signature functions. In the last ten years, conceptual
progress has added two more markers of potential universality to this list: reprogramming energy metabolism and preventing immunological destruction. Tumours reveal a second
level of heterogeneity in addition to cancer cells: a variety of
recruited, apparently normal cells that facilitate cancer cells
acquire distinguishing characteristics [11]. Cancer cells do,
in fact, vary from their healthy counterparts in that they
exhibit a variety of metabolic reprogramming that is inuenced by both the tumour microenvironment and intrinsic
genetic abnormalities. As a result of this metabolic modication, ATP and building blocks for maintaining biosynthetic
capacity and redox status balance are nally provided to cancer cells [12]. To understand cancer pathophysiology and the
signicance of lifestyle factors in reprogramming nutrient
metabolism, this review will talk about changes in metabolic
phenotype and molecular markers. It will also make a strong
case for lifestyle modication to prevent and treat cancer.
2 Molecular Basis ofCancer
Cancer is a state that implies dynamic alterations in the
structure of DNA, in accordance with centuries of research.
The functions of numerous cancer-related genes have been
made known through research on growing embryos and
transgenic mice. Tumour suppressor genes and oncogenes,
which comprise the majority of the altered genes discovered
in cancer, code for parts of the pathways that control how
social and proliferatively active cells behave in the body, particularly the mechanisms by which signals from a neighbouring cell can cause it to differentiate, divide, or die.
Further cancer-critical genes protect the genome's integrity
and preserve it. However, the genetic alterations that enable
malignancies to metastasize, escape the primary tumour, and
grow in other tissues remain largely unexplored.
By sequestering the retinoblastoma (Rb) protein [13]
which controls the p53 protein and cell division [14], DNA
viruses such as papillomaviruses are able to promote the
development of cancer by acting as an emergency halt on cell
division in cells that have experienced genetic damage and
by calling a halt on cell division in senescent cells with shortened telomeres. The Rb protein (pRb) has been shown to be
in charge of a critical G1 checkpoint that prevents cell development and entry into the S phase. Rb2/p130, Rb/p105, and
p107 are three members of the retinoblastoma family that are
collectively referred to as “pocket proteins”. The pRb protein
inhibits gene transcription by directly binding to the transactivation domain of E2F and binding to the promoter of these
genes as a complex with E2F.This is required for the transition from G1 to S phases. pRb suppresses transcription by
altering the structure of chromatin by interacting with proteins such as hBRM, HDAC1, SUV39H1, and BRG1, which
are involved in nucleosome remodelling, histone acetylation/
deacetylation, and methylation, respectively. Cell cycle dysregulation brought on by pRb action deciency may result in
malignant phenotypes. Numerous neoplasia, including
mesothelioma, cervical cancer, and Burkitt’s lymphoma
associated with AIDS, exhibit functional pRb inactivation by
viral oncoprotein binding [15, 16].
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A nuclear transcription factor called p53 promotes apoptosis. Since the p53 gene possesses loss of function mutations in human malignancies (more than 50%), p53 has been
considered as one of the traditional tumour suppressors. The
dominant-negative inhibitor of wild-type p53 is mutant p53.
Indeed, the oncogenic potential of mutant p53 exists.
Malignant cells with p53 mutations occasionally exhibit a
chemo-resistant phenotype. A variety of cellular stressors,
such as DNA damage, cause p53 to build up in cell nuclei
where pro-apoptotic activity can be seen. Activated p53
induced cell cycle arrest to allow DNA repair or apoptosis to
limit the cell propagation with signicant DNA damage via
transactivation of its target genes involved in the induction of
cell cycle arrest and/or apoptosis. Therefore, p53’s DNAbinding ability and tumour-suppressing ability are closely
related [17–19].
As the proliferation as well as metastatic spread of cancer
cells depend on a suitable supply of nutrients, oxygen, and
the elimination of waste products, new growth in the vascular network is vital. Angiogenesis and lymph angiogenesis
are processes that create new blood and lymphatic vessels,
respectively. Both activator and inhibitor chemicals control
angiogenesis. Angiogenic activators and inhibitors have been
found to exist in more than a dozen different protein species.
The level of expression of angiogenic factors reects the
aggressiveness of tumour cells. The identication of angiogenic inhibitors is required to contribute to a decrease in the
morbidity and death caused by carcinomas. Antiangiogenic
therapy has so far been administered to thousands of patients.
Antiangiogenic therapies have not shown long-term survival
benets, despite their theoretical efcacy [20–22].
The nal phases of cancer development include tissue
invasion and metastasis. It describes the way in which primary tumours spread out and inltrate surrounding tissues
before eventually making their way to a distant location to
form new colonies of cancer. The metastasis process, which
is also what causes cancer to spread, is to blame. Alteration
in integrin expression can facilitate cancer cell invasion and
is one typical example. In order to facilitate metastasis, cancer cells have the ability to switch the expression of integrins
used by normal cells to other integrins such as α3β1 and
αvβ3. These integrins can destroy stromal components made
by extracellular proteases. Integrin antagonists, such as the
αvβ3 and αvβ5 inhibitor cilengitide, have demonstrated
promising effects in Phase II clinical studies, and it is currently being investigated in a Phase III trial in people with
glioblastoma [23]. The signicance of understanding how
integrin antagonists affect the tumour and its surroundings is
highlighted by these fascinating clinical advances [24, 25].
Generally, mutations that inactivate particular tumour
suppressor genes as well as activate particular oncogenes are
associated with the stages of tumour progression. However,
various cancer types and even patients who ostensibly have
the same form of the disease might have distinct combinations of mutations, which highlights the random nature of
mutations. Although many of the same genetic defects are
found repeatedly, this suggests that there are only a nite
number of ways to circumvent our defences against cancer
[26].
3 Nutrient Metabolism Reprogramming
inCancer
3.1 Implications ofDierent Nutrients
onCancer
According to estimates, changes in lifestyle and diet can prevent 30–40% of all cancers. Obesity, nutrient-decient diets,
such as concentrated sweets and rened our products,
which affect glucose metabolism, eating red meat, low bre
intake, and an imbalance of omega 6 and omega 3 fats are all
factors in an increased risk of developing cancer. Consuming
plenty of vegetables and fruits as well as ax seed (mainly its
lignan fraction) will decrease the risk of developing cancer.
The health benets of cruciferous vegetables and Allium are
particularly notable, with sprouts of broccoli having high
sulphorophane concentration. Selenium, chlorophyll, vitamin D, vitamin B-12, folic acid, and antioxidants such as
carotenoids (α-carotene, lutein, lycopene, cryptoxanthin,
β-carotene) are protective constituents in a cancer-preventive
diet. Ascorbic acid has few advantages when it is taken
orally, but intravenously may be more helpful. Probiotics and
oral digestive enzyme supplementation are effective anticancer dietary strategies [27]. The energy needs and macromolecular building blocks for maintaining cell development and
survival are met by nutrients, which are essential resources.
As they move through different developmental phases, cancer cells need a number of essential nutrients to meet their
shifting metabolic requirements. Furthermore, variables that
are impacted by both cell-intrinsic and microenvironment
throughout the evolution of cancer determine nutrient
requirements, for which a thorough characterization is yet
lacking [28, 29]. For instance, although in other tissues or
cancerous conditions, glutamine works as a signalling molecule for tumour propagation, glutamine is used as a primary
carbon source to feed into metabolic pathways necessary for
invivo growth of certain tumour cells [30, 31].
3.1.1 Low Fibre
Unprocessed plant meals often contain a lot of bre. There is
one thing that eggs, dairy products, and meat have in common none of them contain bre. Additionally, rened grain
products lose nutritional bre during processing. According
to the report, people who consume the most dietary bre may
experience a slight decrease in the risk of acquiring breast
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cancer and a reduction in the incidence of colon cancer [32].
Little indication of publication bias was discovered, and
dose–response analysis revealed that every increase in
dietary bre consumption of 10 g/day was related to a 4%
[33] and 7% [34] decrease in the risk of breast cancer.
Therefore, the ingestion of dietary bre is strongly linked to
a lower breast cancer risk, especially in postmenopausal
women. High dietary bre intake is linked to a lower risk of
cardiovascular disease and all cancer-related mortality.
These ndings back up the existing advice that a healthy diet
should include a high consumption of dietary bre [35].
3.1.2 Glucose Metabolism
Gluconeogenesis, glycolysis, glycogenesis, and glycogenolysis are only a few of the mechanisms that have glucose
metabolism. The theory that a high glycaemic diet is linked
to cancer has been put to the test through case–control studies and prospective population studies. According to case–
control studies, there is a consistently higher risk of
developing gastric [36], upper aerodigestive tract [37], ovarian [38], endometrial [39], and colon cancers [40, 41] when
a person has a high glycaemic load. Elevated colorectal cancer risk was linked to higher levels of fasting glucose, fasting
insulin, glucose, and insulin levels after two hours following
an oral glucose challenge, and a bigger waist circumference
[42]. Diabetes has been related in numerous studies to an
increased risk of pancreatic cancer [43, 44], colorectal cancer [45–47], and endometrial cancer [48]. It is obvious that
severe glucose metabolism dysregulation is a risk factor for
cancer. Rened sugar, meals containing rened sugar, and
items made from rened our should all be avoided and
removed from a diet designed to prevent cancer. In premenopausal women or women under the age of 50, a high glycaemic load diet and high carbohydrate intake may increase
breast cancer risk [49–51]. Through hyperinsulinemia,
dietary carbohydrate, glycaemic load, and glycaemic index
are hypothesized to affect the risk of colon cancer [52].
3.1.3 Omega-3-and Omega-6 Fatty Acids
Accumulated evidence in animal studies suggests the protective roles of omega-3 fatty acids (DHA, EPA, alpha-linolenic
acid) to be a safeguard in cancer, while omega-6 fats such as
arachidonic acid and linoleic acid have been found to be
cancer-promoting fats [27, 53]. The report suggested a link
between a higher N-3 to N-6 fat ratio and a lower breast cancer risk. The breast tumour suppressor genes BRCA2 and
BRCA1 respond differently to long-chain N-3 and N-6 lipids. When N-3 lipids (EPA or DHA) are applied to breast cell
cultures, the expression of these genes is raised but arachidonic acid has no impact [54]. Due to their numerous biological effects, omega-3 polyunsaturated fatty acids, i.e.
PUFAs are frequently employed in the nutritional therapy of
cancer patients and are regarded as immunonutrients.
Omega-3 PUFAs are vital for maintaining membrane uidity, cell shape, and cell signalling. They have antiinammatory and antinociceptive properties and take part in
the healing process of inammation. They can also stimulate
the G protein-coupled receptors GPR120/FFA4 and GPR40/
FFA1, respectively. Anorexia-cachexia syndrome, paraneoplastic syndromes, depression, and pain are among the problems that cancer patients experience [55]. Several studies
also focus on omega-3 supplements in maintaining muscle
mass and function in cancer patient even if they are undergoing active treatment, which supports their potential signicance in cancer prevention. Omega-3 fatty acids may
contribute to a decreased inammatory response during chemotherapy; however, it is still unknown whether cancer treatment damage may be avoided. Finally, tiny trials revealed
that omega-3 fatty acids boost chemotherapy response rates
[56–58]. Total polyunsaturated and monounsaturated fats
were all strongly correlated with postmenopausal breast cancer. High intakes of omega-6 fatty acids, in particular, were
linked to an elevated risk after accounting for other forms of
fat [59].
3.1.4 Red Meat
High content of processed meat intake was strongly correlated with risk of breast [60], colorectal, rectal, colon, and
lung cancers. High content red meat intake was positively
correlated with the risk of colon, endometrial, rectal, colorectal, hepatocellular carcinoma, and lung cancer [61].
Processed meat consumption and fresh red meat consumption both increased the colorectal cancer risk [62]. Similar
ndings were found for colon cancer, but insignicant relationships were seen for rectal cancer [63]. Eating high content of white meat may reduce the stomach cancer risk,
whereas red or processed meat may raise that risk [64–66].
Low consumption of chicken and a high intake of red meat
are linked to an elevated risk of oesophageal squamous cell
cancer. High meat consumption, particularly processed meat,
is likely to raise the risk of developing oesophageal adenocarcinoma [64, 67–69]. Additionally, there may be no connection between eating sh and the risk of oesophageal
cancer [70].
3.1.5 Flax Seed
Alpha-linolenic acid [71], lignans, and phytoestrogens are
present in ax seeds. They have both hormonal and anticancer properties. Flax has antiproliferative properties in the
breast tissue of breast cancer-prone women and may offer
protection from initial breast cancer. The risk of mortality
may be lower for people with breast cancer [72]. The mammalian lignan precursor secoisolariciresinol-diglycoside and
alpha-linolenic acid (ALA) are abundant in axseed, which
has been demonstrated to have anti-carcinogenic properties
during the early promotion stage of carcinogenesis. While
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the oil in axseed is more potent at the point when tumours
have already formed, the secoisolariciresinol-diglycosidein
axseed seems to be advantageous throughout the carcinogenesis’ promoting phase [73]. Flaxseed downregulates
metastasis of B16BL6 murine melanoma cells in C57BL/6
mice [74, 75]. In the TRAMP (transgenic adenocarcinoma
mouse prostate) model, adding 5% axseed to the diet prevents prostate cancer from spreading and developing [76].
3.1.6 Fruits andVegetables
A diet high in vegetables and fruits protects against cancer,
which is one of the most important messages of contemporary nutrition science. High consumption of raw and cooked
garlic may have a preventative impact on stomach and
colorectal cancers [77]. Greater consumption of Brassica
vegetables was linked to a considerably lower risk of breast
cancer in Chinese women, as determined by the urine ITC
(isothiocyanates) biomarker [78]. To lower the chance of
developing lung cancer [79], ITC from cruciferous vegetables may trigger apoptosis or alter steroid metabolism [80].
There is a negative correlation between eating legumes and
the risk of prostate cancer [81].
3.2 Implications ofNutritional Diet
andLifestyle Modications inDierent
Cancer Types
3.2.1 Colorectal Cancer
Colorectal cancer is the second leading cause of cancer
deaths in the United States, and the third in both genders.
The involvement of lifestyle management in the cases of
colorectal cancer has been a theme of discussion for the past
few years where the diet consumed by people plays a vital
role among which foods with high bre content and rened
sugars are mentionable. Studies suggested that the intake of
rened carbohydrates instead of bre-rich diet has drastically damaged the intestinal ora of the human body, nally
affecting the stool bulk and time of transit of the faecal matters [82, 83]. The precursor lesions of colorectal cancers are
called adenomas which act as assessment points for the risk
of the disease. Few studies also mention an inverse relationship between bre intake and coloreactal cancer [84]. The
intake of rened sugars and high fat causes insulin resistance
and hyperinsulinemia which becomes an aetiology for
colorectal cancer [85, 86] besides IGF-1 being another one
[87]. The mutation of p53in colon polyps is related to the
lifestyle aspects [88]. The subordinate bile acids are found to
be carcinogenic which shows a drastic reduction and recurrence of adenomatous colorectal polyps by the intake of
dietary fats, soluble bres, and green vegetables along with
vigorous physical exercise [82]. The dietary bre enhances
the fermentation process by the natural intestinal ora and
helps in producing short fatty acid chains which have a regulatory action on the cell cycle, apoptosis, and cell proliferation in colorectal cancer [89]. They also show
anti-inammatory properties and diminishes the synthesis of
IL-6, TNFα, and cyclooxygenase 2 (COX-2) gene expressions [90, 91]. Phytochemicals such as terpenes, carotenoids,
thioethers as well as polyphenols are involved in the signalling pathways of cancer and hence intakes of food containing
these like green leafy vegetables of Cruciferae family, garlic,
onion, legumes, and citrus fruits are proved to have positive
results in colorectal malignancy [92]. A European cohort
study stated that doubling the total dietary bres decreased
the incidence of colorectal carcinoma by 40% [93]. Vitamin
B9 (folic acid) has a protective role in the incidence of adenomas and the threat of colorectal carcinoma [94]. It compensates for the loss of tumour suppressor gene DCC and
attenuates the EGFR gene [95]. Vitamin B6, which is found
in many green vegetables, grains, and fruits, has a protective
effect against colorectal cancer as it is found to reduce the
risk by 49% for each 100 pmol/mL rise of serum pyridoxal
phosphate [96]. Vitamin E has α-tocopherol which reduces
the DNA damage in colorectal epithelium [97]. In studies, it
is proved that quercetin reduces the mutation of genes in
colonic mucosa [98]. Consumption of processed red meat
increases the threat of colorectal malignancy as it contains a
higher amount of haeme which is considered carcinogenic
because it degrades down to release iron [99] which promotes the making of reactive oxygen species mainly H2O2
which acts as a main part in genetic mutation and dismantling cytokines [100]. Red meats also produce N-nitroso
compounds which form DNA complexes with telomerestabilizing proteins (TRF2) [101]. It also creates oxysterols
and aldehydes which promote the proliferation of cells [102].
Catering red meat at elevated temperatures promotes the
synthesis of heterocyclic amines which are carcinogenic in
nature [103]. Grape seed extract has properties to reduce oxidative stress and also protects the cell cycle process [104].
Silibinin extracted from the plant Sylibum marianum and the
major component of silymarin is proven to show chemoprotective roles in several cancers including colorectal cancer by
targeting cell cycle, DNA mutation mechanism, processes of
inammation, metastatic signalling, and cell proliferation
[105]. Curcumin extracted from the medicinal plant Curcuma
longa promotes apoptosis by the inhibition of DNA mutation, cell proliferation, and cancer signalling pathways. It
also upregulates the level of glutathione S-transferase and
inuences the concentration of reactive oxygen species
resulting in upregulation of the p21 protein and thereby
restricting the development of malignant cells [106, 107].
Epigallocatechin 3-gallate extracted from tea Camellia
sinensis decreases the growth factors like IGF-1 and blocks
cell proliferation [108]. It also downregulates the MAPK/
kinase signalling pathways [109] and upregulates the pro-
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duction of p53 and p21 thereby promoting apoptosis [110].
The intake of probiotics containing Saccharomyces boulardi,
Bidobacterium animalis, and Bacillus polyfermenticus has
been veried to have anti-cancerous and anti-inammatory
potencies. which decrease the threat of colorectal carcinoma
[111–113]. Alcohol consumption not only has carcinogenic
effect as it causes DNA strand breaks in colonic mucosa cells
and lymphocytes [114] but also reduces the vitamin absorption into the body thereby increasing oxidative stress in the
cells and promoting the procedure of metastatic and cell proliferation [82]. The intake of tobacco increases the risk of
adenomas and the threat of colorectal malignancy as the aromatic and heterocyclic amines are its key ingredients which
cause DNA aberration and mutation [115]. Obesity is another
factor adding to the list as the adipose tissues produce several
hormones which stimulate the T cells and promote insulin
resistance [116] which again contributes to cell proliferation
[117]. So, weight management becomes another way to prevent the threat of colorectal carcinoma. Some studies reveal
that an increase in physical exercise affects the stages of adipohormone leptin which plays an important part in cancer
signalling pathways by MAPK and PI3K/AKT cascade activation [118]. The process of DNA mutation, cell proliferation, and apoptosis pathways are affected by circadian
rhythm and therefore the deprivation of sleep in night shift
workers makes them 50% prone to colorectal cancer [119].
3.2.2 Breast Cancer
Today, most of the females are affected by breast cancer not
only in the United Statesbut also in the European countries
and considered to be the second most dreadful disease among
females [120]. Just like prostate cancer, it is inuenced and
categorized under lifestyle disorder [121]. Breast cancer is
an oestrogen-dependant process and is seen in postmenopause women. During this time, the oestrogen levels
decrease without complete disappearance and continue to be
synthesized by aromatase activity in adipose cells, making
obesity the key factor to the problem [122]. Physical exercise, proper nourishment with regular consumption of vitamins and minerals, plus ceasing the habit of smoking and
drinking act as a major part in the threat of breast melanoma
[120]. The levels of insulin in serum are another factor
responsible for inuencing breast melanoma [123]. The
communication between IGF and oestrogen receptor paths
also affects breast melanoma risk [124]. The treatment of
breast cancer is very pocket pinching and a simple lifestyle
management can be easier, more effective, and economical
in preventing the disease [120]. Alteration in lifestyle management is not only for the women who are at threat of this
disease but likewise for the women who are diagnosed with
it [125]. There are several major factors related to lifestyle
management in preventing breast cancer, the high socioeconomic status being the vital one. The high socioeconomic
status makes the women exposed to a Westernized lifestyle
with the habit of smoking, drinking, fewer kids, and
unhealthy diet [126]. It is been reported that women from
Asian and African countries are less affected by breast cancer than women from American, European, and Australian
countries [127, 128]. Taller women are at greater threat of
breast melanoma than shorter women [129, 130]. Obesity is
linked with insulin resistance which when gained in the middle age directly increases the threat of breast malignancy
[131]. Some cohort studies showed that a signicant weight
loss and proper diet with physical activity have shown positive results for patients of breast malignancy [132, 133]. The
increase in physical exercise in postmenopausal women
decreases the threat of breast melanoma as it affects the levels of oestrogen, insulin, and IGF-1 [134–136]. Physical
activity in post-diagnosed patients of breast cancer shows an
increase in survival rates [137, 138]. Another lifestyle disorder which exposes urban women to the risk of breast cancer
is smoking. Both active and passive smokers fall victim to
this [139–143] especially teenagers. Studies revealed that the
rate of recurrence is 6.7 times higher in females who smoke
than the non-smokers [144]. Females who consume alcohol
are highly prone to risk of breast melanoma [145–147].
Intake of folic acid attenuates the threat of this ailment [148].
Fat intake plus higher BMI directly inuence the disease [49,
50, 149]. On one hand, the intake of red meat and caffeine
induces the disease [150–152], whereas on the other hand
adding vitamins and minerals like vitamin D and calcium to
the daily diet attenuates it [153]. Breastfeeding has been
decreased by urban women due to their professional life and
other recreational involvement. Studies reported that breastfeeding for consecutive 12 months after childbirth decreases
the threat of breast malignancy by 4.3% [154, 155]. Upsurge
in melatonin levels due to night shifts at working place triggers the process of breast cancer in women [156, 157] and
also the associated stress related to it [158]. In an eventual
group study, it has been noted that the use of NSAIDs
declines the danger of breast cancer [159–161]. Several studies also revealed the use of digoxin in the induction of breast
cancer though the recurrence is not reported but the women
prescribed with this drug are suggested for regular check-ups
[162–164].
3.2.3 Melanoma
One of the human organs that is most vulnerable to environmental stimuli is the skin [165] which is the outermost layer
organ. This fact leads us to hypothesize that a person’s everyday habits may affect their chance of developing skin illnesses. The skin is also made up of many types of cells,
including keratinocytes, melanocytes, immune cells, and
adipocytes. Because of this, a person’s everyday habits may
have a signicant impact on their chance of developing cutaneous cancers [166]. The risk of developing cutaneous
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malignancies, such as squamous cell carcinoma, malignant
melanoma, Merkel cell carcinoma, and basal cell carcinoma,
is known to be inuenced by a number of daily lifestyle factors, including smoking, circadian rhythm disruption, fatty
acids, obesity, dietary bre, alcohol, and ultraviolet light
[167, 168]. The epidemiology study found that working
nights increases your risk of developing a number of cancers.
The cutaneous malignancy risk factor is also related to shift
work with circadian disruption [169, 170]. Some investigations revealed a link between current smoking and a higher
occurrence of squamous cell cancer [171–173]. Ginsenoside
Panoxatriol, rutin, vitamins C and E, and these substances all
show promise in protecting skin cells from UVB-induced
cellular damage [174–177]. Vitamins C and E demonstrated
promise for photoprotection in human broblasts exposed to
UVA radiation [178]. Higher levels of circulating vitamin D
have been linked to thinner tumours and longer life in melanoma patients [179–181]. According to the ndings, melanoma cell migration and invasion—a crucial stage in
metastasis—can be prevented by EGCG (epigallocatechin3- gallate), a signicant green tea catechin, by focusing on
the endogenous expression of COX-2 (cyclooxygenase 2),
PGE(2) (prostaglandin E) receptors, and epithelial-tomesenchymal transition utilizing melanoma cell lines Hs294t
(non-BRAF-mutated) and A375 (BRAF-mutated) as an
in vitro model [182]. GSPs (proanthocyanidins) extracted
from grape seed inhibits endogenous expression of COX-2in
melanoma cell lines (A375 and Hs294t) [183]. By blocking
COX-2, PGE2, and PGE2 receptors, berberine prevents melanoma cell lines (Hs294 and A375) from migrating, a crucial
stage in invasion and metastasis [184]. Timosaponin AIII can
prevent the migration of melanoma cells (WM-115 and B16F10 cells lines), a crucial stage in the metastatic process, by
suppressing the production of COX-2, NF-B, PGE2, and
PGE2 receptors [185].
3.2.4 Prostate Cancer
The utmost predominant malignancy in males is prostate
cancer which is mostly seen in the United States compared to
Asia. However, the migration of Asian men to the United
States for professional ventures and adaptation to the lifestyle in the United States makes them fall prey to the ailment
which henceforth proves that lifestyle reasons are responsible for the initiation of the disease [186]. With an increase in
adaptation to Western regime, the occurrence of prostate
malignancy increases in underdeveloped countries [187].
According to the international data, a constructive association has been found between prostate cancer mortality rate
and dietary fats which are found to be comparatively lower in
men from Asia rather than in the United States and Europe
[188]. Some studies have also failed to correlate dietary fats
and the threat of prostate malignancy [189, 190]. The reasons of these results may be determined by the type of fats
used up as omega-3 polyunsaturated fatty acids plus omega-9
monounsaturated fatty acids have a preventive nature in the
progress of prostate cancer, whereas omega-6 fatty acids
promote it [191]. Epidemiological studies reveal the positive
aspects of physical exercise in the reduction of prostate cancer risk by 10–70% [192].
In a study, a bioassay was developed by using the serum
to trigger the cultures of prostate cancer cells. A number of
subjects were selected from the Pritikin Longevity Center
Residential Program where the men were given low-fat diets
including mainly fruits, veggies, and grains and were subjected to physical exercise. The serums were collected and
studied by invivo and invitro methods. The food had different per cents of fats (10–15%), proteins (15–20%), and carbohydrates (65–75%). Plant-based proteins were given with
non-fat dairy products where shes were provided once a
week. The cholesterol content of the diet was less than 100
mg, whereas tobacco, coffee, tea, and alcohols were prohibited. A treadmill test was done before every physical training, the heart rate training and walking (45–60 min) were
practiced [193]. Eleven consecutive days of this routine
reduced the serum-roused LNCaP prostate malignant cell
growth in culture by 30%, and 14 years of nourishment and
workout training in subjected males showed a reduction in
the growth of LNCaP cells by 15%. LNCaP is an androgensensitive cell line derived from males suffering from prostrate adenocarcinoma [193]. Another androgen-dependent,
LAPC-4, was seen to be reduced by nourishment and physical workout [194].
A signicant drop in serum insulin and a rise in sex
hormone- binding globulin were seen in males undergoing
low-fat diet and physical training. The sex hormone-binding
globulin lowers the free testosterone plus oestradiol stages in
serum and acts as a factor to reduce the growth of LNCaP
cells because this is androgen dependent and both testosterone and oestradiol bind to its receptors [195]. Another study
reported that testosterone, insulin, and oestradiol can promote the LNCaP cell development individually. However,
the nourishment and workout subjected individuals when
treated with these hormones, a 50% reduction in LNCaP cell
development was observed [193, 196].
One of the most potent mitogens for prostate is IGF-I
which is a peptide development aspect formed from the liver
and regulates the growth of cells, cell differentiation, and
apoptosis process [197, 198]. There are six different proteins
related to the IGF axes among which IGFBP-3 is abundant in
nature and binds with 90% of the circulating IGF-I where no
change was noted in males subjected to a special low-fat diet
and exercise, but high after abstaining [199].
Accumulating evidence suggests that a low fat diet and
physical training diminished the serum IGF-1 levels and
increased IGFBP-1 levels relative to baseline. These changes
are predicted to be the reason for modulating serum insulin
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levels and its effect on liver [199]. IGF-I has been stated to
suppress apoptosis besides regulating the growth of LNCaP
cells [200]. In the cell culture invitro study, no sign of necrosis was established in foetal bovine serum of the control
group and nourishment and workout subjected group [194].
Very little apoptosis was noticed in serum-stimulated LNCaP
cells because of higher IGF-I and lower IGFBP-1in the control group. This study also claries the reason why the higher
threat of prostate malignancy is ubiquitous in the United
States [194].
The exercise including calisthenics, swimming, and strenuous training of 40–50 minutes at a continuous stretch
showed lower levels of serum insulin and IGF-I, whereas
IGFBP-1 was advanced in equally exercising and exercise
plus diet groups. The rate of apoptosis was higher in nourishment plus workout trials than in the other groups [201].
Smooth functioning of the p53 gene is a characteristic
feature of every prostate cancer at its early stage which is
found to become defective in the later stages [200]. IGF-1
supressess the normal function of p53 thereby activating the
downstream signalling axes associated with cell cycle arrest,
DNA repair and apoptosis [202].
In a study, patients with prostate malignancy were prescribed with very low-fat diet including 10% fats from soy,
sh oil containing omega-3 fatty acid (3 g/day) and vitamin
E (400 IU/day) followed by aerobic exercises like walking
and jogging for 30–60 min (6 days/week) and yoga and
breathing exercises (1 h/day) [203, 204]. The serum collected from these patients displayed a reduction in LNCaP
cell growth by 60% in the nourishment plus workout set
[204].
Intake of lycophene-rich food and tomatoes can diminish
the threat of prostate malignancy and its growth [205–207].
Foods like guava, apricots, watermelon, pink grapefruit,
brussels sprouts, cabbage, broccoli, cauliower, watercress,
kale, onions, leeks, garlic, scallions, and chives may also
reduce the risk of this ailment [208–210]. Genistein and biochanin A are the precursors derived from soy that prohibit
the growth of hormone-insensitive and sensitive cancer cell
lines by decreasing the level of PSA in LNCaP prostatecancer cell lines [211]. Genistein interferes with the tyrosine
kinase growth receptors and receptors disturbing topoisomerase II, hindering angiogenesis, and stimulating apoptosis
[211]. The levels of testosterone were noted to be decreasing
in males from Japan who were taking genistein [212]. A
slight change in the concentration of these hormones in the
serum for months, years, and decades slows down the progress of prostate cancer [189, 190]. Several studies including
men with Gleason scores below 7 who were prescribed soy
in the diet and subjected to physical training gave positive
results after one year of treatment for prostate cancer [211].
Flaxseed, canola oil, soybean oils, and axseed oil comprise
alphalinolenic acid (ALA), which is an omega-3 fatty acid,
and lignans which is a plant oestrogen. The lignans showed
anti-cancerous activity invitro in prostate cancer cell lines
[76, 213]. A cohort study in the Netherlands showed that an
increase in the intake of ALA reduced the threat of prostate
malignancy [214]. Another research reported that the intake
of axseed by males suffering from prostate cancer with a
Gleason score below 6 showed reduced cancer cell proliferation and preferment of apoptosis in the prostate gland besides
reducing the cholesterol levels [215]. Fish contains eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and
vitamin D.The consumption of sh oil lowers the threat of
prostate malignancy [216–218]. Fish consumption includes
preserved tuna, dark sh meat like mackerel, salmon, swordsh, bluesh, sardines, and others which reduced prostate
cancer by 44% [219]. Nuts have elevated levels of omega-3fatty acids, vitamin E, avonoids, minerals like magnesium,
potassium and selenium [210, 220] and are proved in lowering the threat of prostate malignancy [210]. Some epidemiological studies reported that physical workouts dipped the
threat of prostate malignancy as obesity is linked with the
disease [221]. Physical exercise boosts the mental health of
the patient distressed from prostate malignancy and makes
the body stronger to withstand the treatment the patient has
to undergo during the therapy [222]. Reduction of the smoking habit has been reported to have positive results in curing
prostate malignancy [223–225]. Some dietary supplements
like the addition of zinc to diet show benecial results in
prostate malignancy risk [226].
3.2.5 Lung Carcinoma
This type of cancer has a high proliferation rate and low survival chances but can be restricted by nutritional diets and
lifestyle modications. Various nutritional diets can prevent
and treat these diseases. Different lifestyle activities, like
smoking cigarettes and intake of tobacco in various form,
increases the oxidative stress in the internal organs thereby
triggering the process of lung carcinoma [227]. There are
different bioactive factors derived from adipose tissues
which have a signicant biological role in implicating lung
cancer. Some adipocytokines induce the process which
results in the development and proliferation of lung carcinoma. Besides, it should also be noted that all the adipokines
are not tumour stimulants. Adiponectin regulates the cell
growth and concentrations of inammatory cytokines [228].
Increase in the levels of adiponectin by nutritional supplements has been used as a newly introduced therapeutic strategy for ghting this disease. Intake of foods rich in
antioxidants and anti-inammatory potential is showing
fruitful results in the prevention of the deadly ailment [228].
Oxidative stress is the major factor in the carcinogenic process. It initiates, promotes, and progresses the process of
cancer [229]. It is mainly the reactive nitrogen species (RNS)
and reactive oxygen species (ROS) which are not compen-
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sated by the antioxidant system of the cells [230]. The enzymatic antioxidant defence system, which gets dismantled by
ageing, malnutrition, and lack of physical exercise [231], is
the root cause of higher ROS levels. The reactive oxygen
species promote the expression of genes that control the differentiation and growth of the cell. The hyperactivity of the
reactive oxygen species is generally caused due to mutation
and chromosomal aberrations which leads to the degeneration of cells and stimulates carcinoma [232]. Smoking cigarettes creates inammation in the lung epithelium which
produces inammatory cytokines and ROS resulting in oxidative stress which becomes the main aspect for the progression of tumours [233–237]. Several air pollutants activate the
MAP kinase signalling pathway which produces inammation in the lungs thereby causing carcinogenic effects in nonsmokers [238]. Obesity on the other hand promotes
carcinoma as the adipocytes trigger cell proliferation. Several
studies support the hypothesis that adiponectin (Acrp 30), an
oligomer, helps in preventing lung cancer by inhibiting cell
growth and concentration of inammatory cytokines [239].
In a study, it was revealed that the consumption of cereals,
vegetables, fruits, and dietary bres in high quantities lowers
the threat of lung carcinoma [240]. The utmost effective is
the ketogenic diet that increases the levels of adiponectin
[241]. The addition of medicinal plants and bioactive compounds in the diet like anthocyanins, walnut, curcumin, soy,
resveratrol, and dihydromyricetin increases the levels of adiponectin in blood which prevents lung cancer [242]. In earlier studies, it is established that the Mediterranean diet
lowers the threat of cancer and reduces the death rate [243].
These include mainly vegetables, fruits, seeds and nuts, olive
oil, legumes, dairy products, eggs, poultry, and wine which
are rich antioxidants and decrease the concentration of reactive oxygen species and detoxify the system [244]. Foods
with avonoid contents like whole grains, olive oil, vegetables, fruit, nuts, coffee, tea, and red wine have high free radical scavenging property which protects the DNA from
damage [245–248]. Cinnamal aldehyde from cinnamon oils
overpowers the initiation of NF-KB in inammation by TNFα
[249]. Foods rich in carotenoids are natural antioxidants
which neutralize the reactive oxygen species [250]. The
presence of phytochemicals like isothiocyanate and phenolic
compounds in plant-based food helps to detoxify the
enzymes, metabolizes the carcinogens, and improves the
immune system [251]. The intake of non-starchy food and
food comprising selenium and quercetin lowers the threat of
lung carcinoma [228]. A Danish study shows the higher the
intake of nutritional food, the lower the threat of lung cancer
which was supported by a similar study in Finland, where the
intake of food rich in carotenoids lowered the threat of lung
carcinoma [252, 253]. Olive oils and sunower oils contain
α-tocopherol which helps in the reduction of the risk of lung
cancer [254]. Phytoestrogens and glucosinolate hydrolysed
products exist in many fruits and vegetables and help to
reduce the process of lung carcinogenesis [255, 256]. There
are also roles of vitamin B, vitamin C, and phytochemicals in
modulating epigenetics which provides promising interventions in the chemoprevention of lung carcinoma [257–260].
The intake of folate-rich foods shows positive results in
smokers as it methylates the promoter of the tumour suppressor gene [261, 262]. Vitamins B12 and D, magnesium, manganese, niacin, and omega-3 fatty acids protect the
methylation of gene and also prove to be potent antiinammatory agents that show an essential part in the protection of carcinogenesis of lungs [263, 264]. Figure2 shows
a schematic diagram related to the prevention of lung carcinoma. A decrease in the intake of red meat shows a positive
effect in preventing lung cancer [265] as it produces polycyclic aromatic hydrocarbons (PAHs) and heterocyclic amines
(HCAs) during the process of catering which have carcinogenic properties at higher temperatures [266, 267]. Bacteria
in cheese and dairy products produce lactic acid and can
inuence the initiation of lung cancer by hampering the
immune system [268].
4 Modifying Lifestyle Reduces theRisk
ofDeveloping Cancer
The underlying common denominator among most malignancies appears to be lifestyle, including smoking, a diet
high in fat and processed sugar, and lack of exercise. The
majority of cancers may be prevented by altering these lifestyle variables, which are simple to do. One could signicantly alter growth factors and hormones known to be linked
to cancer by consuming a diet high in fruits, vegetables, and
whole grains with little to no meat, predominantly chicken or
cold-water sh, and engaging in 45–60min of daily exercise
[82]. After adjusting for smoking behaviours and cigarette
use, a large Norwegian study with 81,516 men and women
over the course of 19 years reported that males who walked
or cycled for at least 4 h per week had a 25% lower chance of
developing lung cancer [269]. Beta-carotene has the capacity
to act as an antioxidant; other micronutrients with this capability, in particular vitamins E and C and selenium, have also
been reported to lower the chance of developing lung cancer
[270]. About 50,620 incident malignancies accumulated
throughout the 10.1 years of follow-up for a total of 755,459
individuals (median age, 62 years [range, 32–91 years]; 53%
female). Seven out of 15 cancer types examined had a statistically signicant lower risk in people engaged in the recommended levels of physical activity (7.5–15 MET h/week),
including breast cancer (6–10% lower risk), colon cancer
(8–14% lower risk in men), kidney cancer (11–17% lower
risk), endometrial cancer (10–17% lower risk), liver cancer
(18–27% lower risk), myeloma (14–23% lower risk), and
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Fig. 2 Diagrammatic representation showing different sources of food preventing lung carcinoma (‘+’ = accelerates; ‘–’ = retards)
non-Hodgkin lymph (11–18% lower risk in women) [271].
Recreational physical activity is linked to a lower risk of rectal cancer in older men and women as well as a signicantly
lower risk of colon cancer as time spent participating in it
increases [272, 273]. However, there is evidence that suggests men who engage in high levels of vigorous activity
may have a decreased chance of developing metastatic prostate cancer. Physical activity is unlikely to have a signicant
impact on the incidence of all cases of prostate cancer [274,
275]. Changes in lifestyle are crucial for preventing breast
cancer. Such adjustments include losing weight, moving to a
ease is recommended. Furthermore, a diet high in carbohydrates increases the incidence of breast, colon, ovarian, and
endometrial cancers, while an increased consumption of red
meat increases the prevalence of colorectal, endometrial, and
lung cancers. Additionally, lignan and phytoestrogen from
axseeds also play an important role in reducing the progression of breast and prostate cancer. Overall, adopting a diet
containing whole grains, fruits and vegetables, high bres,
low carbohydrates, and daily exercise will potentially alter
the hormones and growth factors associated with cancer sig-
nalling axes, nally lowering the progression of cancer.
healthy diet, cutting out needless medications, etc.
Additionally, lifestyle modications can lower the recurrence rate and improve survival rates in women who have
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5 Summary
This chapter provides a vivid description of the protective
mechanisms of lifestyle modications and natural nutritional
diets in mitigating cancer progression. This is evident that a
diet high in carbohydrates and low bre, red meat, smoking,
and lack of physical activity plays a signicant role in developing cancer. Intake diets possessing high bres which
decrease the chances of breast cancer and cardiovascular dis-
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