Nutrigenomics: Epigenetics and cancer

prevention: A comprehensive review

Ayesha Nasir, Mir. M. Hassan Bullo, Zaheer Ahmed, Aysha Imtiaz, Eesha Yaqoob,
Mahpara Jadoon, Hajra Ahmed, Asma Afreen & Sanabil Yaqoob

Ni Luh Eka Suprapti

C175181005

Pembimbing
dr. Agussalim Bukhari, M.Med, PhD, Sp.GK (K)

ALLPPT.com _ Free PowerPoint Templates, Diagrams and Charts

ABSTRACT
Due to change in lifestyle and
food habits, people are more at
risk of diet-related diseases and
Nutrigenomics is relatively fresh
cancers. It is also established
discipline, but possess an
that dietary modifications
enormous potential that can
significantly reduce the risk of
apply for prevention and
diseases.
management of certain
carcinomas and diseases.

This review enables us to generate

useful information for scientists
and health professionals regarding It influences health conditions
the role of Nutrigenomics in the of individuals and susceptibility
prevention of diet and lifestyle- of disease by defining the
related diseases like cancer. metabolic response and gene
expression.
ABSTRACT
Omega 3 fatty acids are the best
Epigenetic modifications can
example of nutrients and gene
perform a significant role in
interaction not involving DNA
disease occurrence and
methylation while certain
pathogenesis. DNA methylation
bioactive food compounds have
and chromatin remodeling are
a proven role in cancer
the most common epigenetic
prevention through an
mechanisms.
epigenetic mechanism.

Moreover, minerals and vitamins

Dietary polyphenols substantially involve regulatory processes.
take part in prevention of oral, Zinc, Selenium and folate
breast, skin, esophageal, involve in DNA repairing
colorectal, prostate, pancreatic process have anticancer
and lung cancers. properties. Consumption of
multivitamins prevents
methylation of cancer cells.
Introduction and background
In this regard, human
The knowledge about genome project had
The genetic revolution the genes has improved played a vital role to
has highlighted the health diagnosis and determine mutual
role of diet in the enhanced the relationships
health and wellbeing. understanding of between nutrient,
genomic medicine. genes and disease.

Nutrition research has Due to the change

progressed from in lifestyle and food
physiological and habits, people are
epidemiological facets to more at risk of
genetics aspects and chronic diseases and
molecular biology as certain sarcomas or
well as nutrigenomics. cancers.
Introduction and background

According to the epidemiological

data, a large portion of the human
cancer is significantly associated
with lifestyle and diet.

The diet has the meaningful impact

on numerous stages of cancers.

This review enables us to improve

our understanding regarding the
importance of nutrigenomics in the
prevention of cancer.
Nutrigenomic or nutritional genomics
Nutrigenomic or Nutritional genomics has
become an important discipline due to its
significant role in nutrition and medical
science.

It is a useful remedy for cure and prevention

of the numerous types of cancers along with
chronic diseases.

Nutrigenomic → multidisciplinary knowledge

deals with the effect of foods on our genes
and response of individual genes towards
nutrients absorbed through various foods.
Nutrigenomic or nutritional genomics
It has long been recognized that human response differently to
the food they consume. Food components not only affect health
but also metabolism, cell, and organs as well.

Nutrient
metabolism
may differ
Effect of
among
nutrients on Nutrigenomics individuals
gene
genotypes
expression
hence effecting
health
differently.
Principles of nutrigenomics
Epigenetics
Epigenetics was first
described by Conrad
Waddington in 1942 is a
combination of two words Currently, it deals with the
epigenesis and genetics chromatin remodeling and
involving developmental DNA methylation.
events from fertilization
to the whole organism.

Epigenetic modifications can perform a significant role

in disease occurrence and pathogenesis including
cancer.
Epigenetic molecular events

Epigenetic events involve

three types of regulations, Chromatin structure is said to
(1) Histone modification be a repeated set of
(2) DNA methylation nucleosomes that contain
(3) gene expressions by DNA and proteins called
nc-RNA. histones.

Histone is a complex of eight proteins → octamer

structure. The histone octamer consists of two
fragments each containing histones H2A, H2B, H3,
and H4. H1 histone is called linker histone that links
physically, connects nucleosomes with linker DNA.
Chromatin structure may undergo changes during
metabolic events.
Epigenetic molecular events
DNA methylation comprises Both DNA strands undergo
covalent amendments in methylation of cytosine
cytosine pairs at 5 carbon through methyl donors
position of CG S-Adenosyl methionine and
dinucleotides → CPG DNA methyltransferase
dinucleotides. enzymes in replication
process parent strand is
methylated but the
daughter strand remains
un-methylated.

DNA methyl enzymes are of two types one is

responsible for methylation while other
maintains the methylation process once it
established.
Mutations in cancer
Programmed cell death is a normal mechanism in the
human body.

Mutations in genetic pathways lead to abnormal cell

production or neoplasm.

Carcinogens present in diet and environment causes

modifications in cell cycle regulation and leads to
abnormalities.

Carcinogenesis → the accumulation of mutagens or

epigenetic events in genes,in other words, proto-
oncogenes become activated to oncogenes and there is
the silencing of tumor suppressor genes (TP35) in the
result of mutational shift and chromosomal
rearrangements.
Mutations in cancer

Certain bioactive food ingredients or micronutrients are

normally involved in DNA methylation, gene expressions,
histone modifications, biological and metabolic regulatory
pathways.

Deficiency of any key nutrient, the absence of methyl

donors or hindrance in methyltransferases can lead to
mutations in genes by activating promoter genes and DNA
hypo or hypermethylation resulting into silencing of
tumor suppressor genes with age and cell
proliferation leads to cancer development.
Diet and cancer
According to epidemiological and clinical studies dietary factors
are involved in cancer development.

Dietary mutagen leads to Dietary based regimens and

mutations in normal dietary components also have
pathways as they are a preventive effect against
involved in many cancer as DNA metabolism
biological and and repair depends on
pathological conditions. dietary factors served as a
cofactor in metabolic
pathways.

Certain bioactive food compounds have proven role in cancer

prevention through epigenetic mechanism genetic modification
and nutrient-gene interactions and prevention from damage
due to oxidative stress.
Diet and cancer

Not only food preferences Plants phytochemicals and

but also the amount of polyunsaturated have
specific food components proven role in diet and
also affects genes. cancer relationship.

Not only these but also vitamins and

minerals have a significant part in it.

Minerals and vitamins from diet

involve in regulatory and enzymatic
processes.
Diet and cancer
The deficiency of
micronutrients leads to
abnormalities.

Zinc and folate involve in DNA

repairing process.

Some of the compounds have proven role in epigenetics ,

may interact with genes other than DNA repairing and
methylation, have a protective role against oxidative stress
and some inhibit cell proliferation by modifying the
inflammatory process.
Nutrigenomics/epigenetics: role of dietary
components in cancer prevention

In nutrigenetics and nutrigenomics, nutrients interact with

genes involved in the genesis of cancer while epigenetic role
includes nutrients specifically targeting DNA methylation and
histone modifications.

In this review, we only discuss only those nutrients that have

proven potential effect in preventing cancer by interacting
with genes other than DNA methylation (Nutrigenomics) and
epigenetics (DNA methylation and modifications).
Omega 3 fatty acids
It is found in fatty and greasy
fish while some amounts
present in oils extracted from
plants like flaxseed oil.

Omega 3 fatty acids are They have also proven

proven anti-inflammatory their nutrigenetics role in
agents against many which they interact with
diseases including genes involved in
cardiovascular and cancers inflammation and cancers.
Marine n-3 unsaturated fats
The various animal in have been likewise producing
vitro studies has shown defensive effect against
the effect of omega 3 carcinoma of the breast in
fatty acids especially postmenopausal women. This
docosahexaenoic acid inhibitory effect is
against prostate cancer. associated with the degree of
lipid peroxidation
produced in tumor
tissues or cells.
Dietary polyphenols
Polyphenols also are known Several mechanisms have
as polyhydroxy phenols are been found by which dietary
found in fruits and vegetables polyphenols prevent certain
and present in human diet → disease including their
dietary polyphenols. epigenetic role in cancer
prevention by remodeling of
chromatin material and
activation of gene silencing.
Cancer preventing the effect of
dietary polyphenols may be All these characteristics of
outlined due to their ability to polyphenols can
inhibit DNA methyltransferase fundamentally alter the
and to modify histones. epigenome of tumor cells
and are perceived as
interesting potential
outcomes for cancer
prevention.
Epigallocatechin

Polyphenols One subcategory Epigallocatechin

from tea and of tea polyphenols accounts for 50%
green tea have are catechins that of all the bioactive
include, compounds
proven their role epicatechin 3 present in tea
in many diseases gallates, studied for
including cancer. epicatechin, and anticarcinogenic
epigallocatechin. properties.

A number of studies significantly showed a positive correlation

with consumption of epigallocatechin and prevention of oral,
breast, skin, esophageal, colorectal, prostate, head, neck and
pancreatic cancer.
 Curcumin
Curcumin is a polyphenolic compound present in commonly used spice
turmeric and curry has proven its role as a wound healer, anticancer, anti-
inflammatory agents with other health benefits.

- Curcumin inhibits DNMT action by covalently binding and blocking the

reactive sites of thiolate of C1226 of DNMT1.
- Curcumin has an epigenomic impact on genomic DNA of leukemia cells by
global hypomethylation of MV411 cells after curcumin intake.
- Curcumin can perform an anti-inflammatory → Halogenated cytosine
initiates these kinds of impacts that stimulate 5-methylcytosine in DNA
methylation and shows a significant association between inflammation and
epigenetic alterations.
- Curcumin also works as histone modifying agent and also has potential to
inhibit HDAC and HAT while this effect is less as compared to other dietary
polyphenols.
 Apigenin

Apigenin is plant flavone

(4, 5, 7- Apigenin prevents from cancer →
trihydroxyflavone), inducing apoptosis in various
present in many fruits cancerous cells including breast,
Apigenin is known hepatoma, skin, thyroid, prostate
and vegetables. Parsley, potent anticancer agent
celery and dried and leukemia by inhibiting DNA
→ interacting with replication; inhibition of protein
chamomile flowers also cancerous cell genes.
contain ample amount of kinase, caspase activation, ROS
apigenin. generation and mitochondrial
damage.

Apigenin also inhibits

In study conducted by Shankar et al → feeding invitro DNMT and
of 20 and 50 microgram apigenin per day for HDAC-1 activity and
20 weeks in TRAMP mice had reduce prostate reduce tumor growth
cancer by inhibiting activation of NF-jB through its epigenetic
modifications.
Resveratrol
• Resveratrol is a bioactive compound known for its
anticancer ability and it is available from red grapes,
wine, blueberries, and mulberries.

• Anticancer properties of resveratrol have a preventive

role in lungs, skin, prostate and breast cancer.

• It has also an epigenetic role to prevent silencing of

tumor suppressor genes BRCA1.
• Impotent to hinder MGMT promoter methylation and
RARb2 in MCF-7 cells.
Genistein
Genistein is isoflavones belongs to the largest class of polyphenols known as
flavonoid group. They are abundantly found in soybeans and also known as
phytoestrogens or an estrogen-like compound having anti-cancer properties.

Genistein has proven their dose-dependent epigenetic role in DNMT inhibition,

gene transcription, and histone acetylation.

Genistein combined with DNA methylation inhibitors or different DNMTs can

improve the reactivation of qualities silenced by methylation. It was determined
that genistein hinders DNMT1, 3a, 3b, and expression of hTERT. Genistein
builds acetylation by enhancing HAT action.

Various studies have determined that genistein initiated hypomethylation and

hyperacetylation rejuvenate tumor suppressor genes in the prostate cancer cells.
Micronutrients (minerals and
vitamins)

Minerals and vitamins are an essential part of the

human diet and a huge range of micronutrients
(Minerals and Vitamins) available subsequently.

Both minerals and vitamins play an important role in

metabolism based reactions, they regulate certain
important events by acting as a cofactor and key
nutrient.
 • DNMT catalyzes the transfer of methyl group from S-adenosyl
methyltransferase to particular sites in DNA and in return, it takes its
deficient molecules from folic acid, vitamin B12, B6, choline, and
methionine hence it is highlighting the role of vitamins in the
epigenetic mechanism.
Vitamin • Significant protection against methylation in cancer cells of the lung
was also observed after consumption of multivitamins.

• Selenium → recognized as epigenetic mineral found in nuts and beef.

Se possesses anticancer properties due to antioxidant effect and DNA
repairing mechanism along with pro-apoptotic ability.
• Zinc → an important mineral act as a cofactor in DNA repair genes

Mineral (OGGI) that are responsible for removal of oxidized guanine.

• Magnesium → acts as a cofactor for various DNA polymerases.
 Gaps and challenge and future
perspectives

Nutrigenomics came into force in Epigenetic variations help researcher to set

biomarker profiles for different types of
order to step forward from physiology cancers as they are the primary events in
and epidemiology to molecular cancer development and give consideration
genetics. about nature and course of modifications.

Dietary phytochemicals have a strong Epigenetic modifications provide

potential to modulate all major better understanding of global
epigenetic pathways which involves patterns, chemo preventive strategies
methylation of DNA and modification and role of dietary phytochemicals to
of histonesand miRNA. inhibit the cancer progression.

Overall there is need to develop and implement

multidisciplinary approaches to totally reveal the relationship
between health and effect of bioactive food ingredients in
succeeding actual personal based nutritional recommendations
of bioactive food ingredients.
Conclusion

It is well established that food and dietary modifications significantly

reduces the risk of diet and lifestyle related diseases.

Nutrigenomics in this regard is relatively fresh discipline but possess an

enormous potential that can apply for prevention and management of
certain carcinomas and diet-related diseases.

Epigenetic modifications can perform a significant role in disease

occurrence and pathogenesis including cancer.

DNA methylation and chromatin remodeling are the most common

epigenetic mechanisms. Certain bioactive food compounds and nutrients
have proven role in cancer prevention through an epigenetic mechanism,
genetic modification, and nutrient-gene interactions.
THANK YOU