SNT 2023

NUTRITIONAL BIOCHEMISTRY
CHAPTER 8:
CANCER

Tasneem binti Shaari

tasneem_shaari@msu.ed
u.my

Cancer is a disease that involves the acquisition of

mutations in several specific genes in the cell.
Sum of these mutations allow the cells to divide
and multiply
Invade surrounding tissues an organs
Mutations in APC, RAS, p53 and cadherin proteins
are closely related to the development of cancer
cells.

 Cancer

is defined as

disease in which the normal control of cell

division is lost, so that an individual cell
multiplies inappropriately to form a tumour.

PATHOPHYSIOLOGY OF
CANCER

PATHOPHYSIOLOGY OF CANCER:

Most cancers develop from a single cell that grows

and divides more than it should
Resulting in the formation of a tumour or cancer.
Cancers growing in most tissues take the form of a
lump that grows, invades local non-cancerous
tissues, and may spread to other parts of the body
through the bloodstream.

 Cancers

arising in the cells of the blood, such

as leukaemia, do not form a lump
because

the cells are floating freely throughout the

blood stream.

Most

deaths due to cancer are caused by the

spread of the cancer from its site of origin
into adjacent areas and to other parts of the
body.

The

transfer of the cancer from one site to

another site not directly connected with it is
called metastasis.

 The

change from a normal cell into a cancer,

termed carcinogenesis, is a multi-stage
process and can take several decades;
consequently

incidence of most cancers is highest

among the elderly.

Carcinogenesis

is fundamentally a process of
alterations (mutations) in DNA.

 Typically

the change from a normal cell to

cancer requires mutations in a few different
genes.

Mutations

in genes involved in the control of

cell division and cell death (apoptosis) are
especially important.

Some

mutations are inherited, while others

are caused by factors such as ionizing
radiation, chemical carcinogens and viruses.

 The

key genes in carcinogenesis can be

considered in two classes:

Oncogenes,

genes that when over-activated

lead to over-stimulation of cell growth and
cell division; and

Tumour

suppressor genes, which normally

limit the rate of cell division.

CARCINOGENESIS

 Carcinogenesis

is the change from a normal

cell into a cancer. It is fundamentally a
process of alterations (mutations) in DNA.

The

key genes in carcinogenesis:

Oncogenes

Genes that when over-activated lead

to over-stimulation of cell growth and cell division
Tumour suppressor genes Genes that normally
limit the rate of cell division.

CANCER AND ITS

CONSEQUENCES

 The

effects of tumor growth can be local or

systemic

Consequences

if tumor
countered by treatment:
Obstruction

growth

is

not

of blood vessels, lymphatics or ducts

Damage to nerves
Effusions
Bleeding
Infection
Necrosis of surrounding tissue
Death of patient

 The

cancer cells may secrete toxins locally or

into the general circulation

Both

endocrine and non-endocrine tumors

may secrete hormones or other regulatory
molecules

Tumor

marker any substance which can be

related to the presence or progress of a
tumor.

Biochemical effects of tumor growth

LOCAL EFFECTS OF TUMORS

Local growth of tumor can be can cause a wide

range of abnormalities in commonly requested
biochemical test.
The liver is often the site of metastatic spread of
tumor.
Metastatic spread of tumor to an important site
may precipitate complete system failure.
Destruction

of adrenal cortex by tumor causes

impaired aldosterone and cortisol secretion
potentially fatal consequences.

LOCAL EFFECTS OF TUMORS

Large tumors may not have an extensive blood
supply
Tumor cells meet their energy needs via glycolysis
May result in generation of a lactic acidosis

Renal failure may occur in patients

malignancy for the following reasons:
Obstruction of urinary tract
Hypercalcaemia
Bence-Jones proteinuria
Hyperuricaemia
Nephrotoxicity of cytotoxic drugs.

with

ECTOPIC HORMONE PRODUCTION

It is a characteristic feature of some cancers that

they secrete hormones.
Referred as ectopic hormone production.

Small cells carcinomas are the most aggressive of

the lung cancers
Most likely to be associated with ectopic hormone
production.

ECTOPIC HORMONE PRODUCTION

Evidences

Condition

of ectopic hormone production:

resolves after surgical removal of

tumour or irradiation.
Demonstration that hormone level in arterial
supply to tumour is less than in venous
drainage.
Hormone may be extracted from tumour.
Histochemical demonstration of tumour cell
secretory granules and mRNA for hormone.

CANCER CACHEXIA
Notes on whiteboard

ALCOHOL CONSUMPTION
AFFECTS DEVELOPMENT
OF CANCER

High alcohol consumption causes cancers of the

mouth, pharynx, larynx, esophagus and liver.
Even moderate alcohol intakes causes a small
increase in the risk for breast cancer.
This effect of alcohol may act through enhancing the
action of carcinogens or via the effects of
acetaldehyde which is produced when ethanol is
metabolized.
The increase in breast cancer risk due to alcohol
intake may be from effects on estrogen metabolism.

GENETIC CHANGES THAT

RESULT IN CANCER

DNA DAMAGE
DNA

consists of two molecules of singlestranded DNA (ssDNA) wrapped together

in a fiber called the double-stranded helix
(dsDNA).

Damage

can be done to DNA by a number

of separate and distinct processes.

Processes:
Spontaneous hydrolysis of the amino group of
cytosine. This results in cytosine (C) being
converted to thymine (T) plus free ammonia

Damage due to hydroxyl radicals. Small amounts of

reduced iron bound to our DNA may allow the
Fenton reaction to occur, thus producing HO- in the
immediate vicinity of DNA. The HO- radical attacks
guanine (G) residues, producing residues of 8-oxoguanine (oxo-G)

Covalent damage due to naturally occurring

components of the diet. Compounds in cooked meat,
for example are converted in the body to reactive
chemicals, which in turn attack our DNA
Covalent damage due to chemicals acquired from
cigarette smoke.
Covalent damage due to ultraviolet rays from the
sun
Rare mistakes made by DNA polymerase during
DNA synthesis (replication).

Sources:
Workers in chemical plants, farm workers,
and victims of nuclear powerplant disaster
acquire damage from specific sources
(synthetic chemicals and radiation) that do
not affect the general population.

P53
Role:
To momentarily halt the progression of the
cell cycle, so as to give various DNA repair
enzymes a chance to complete their job
Mutations

of this protein can occur either

in spontaneous or inherited cancers.

Half

of cancer cases are caused by the

mutation of p53.

THE ASSOCIATION OF P53

MUTATION WITH CANCER
DEVELOPMENT IN HUMAN
Mutations

in p53 constitute a necessary

step in the conversion of many types of
normal cells to become invasive.

The

defect in p53 increases the rate of

accumulation of mutations in many other
genes

THE ASSOCIATION OF P53 MUTATION

WITH CANCER DEVELOPMENT IN HUMAN
One

of the gene mutations will promote

the conversion of the fast-growing cancer
cell to a fast-growing invasive cancer cell

Most

of the mutations in p53 occur within

the DNA binding region and tend to result
in changes in certain types of amino acids

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