Download Risk Factors for cancer

Chapter 3
Cancer
Definition:
Cancer is the growth of
abnormal cells that tend to
invade neighbor tissue and
spread to distant body sites (
uncontrolled cellular
proliferation that knows no
limits and serves no purpose).
There are more than 100
forms of the disease.
For a cell to become
cancerous, the following
genetic alterations must occur :
- prompt cell growth;
- inactivate genes (normally
slow growth);
- allow cells to keep dividing,
- allow cells to live on with
abnormalities (stop
apoptosis).
- recruit normal cells to
support and nourish them,
and
- prevent the immune system
from destroying them.
Physiologic Concepts
A. Cellular Reproduction
 All cells reproduce during
embryogenesis, only certain
cells continue to do so after the
first few months following an
after birth.
 Cells that reproduce, such as
liver, skin, and GIT cells, split
into two new daughter cells.
 Cells that do not reproduce
after birth (skeletal muscle,
nerves) do not go through this.
B. Cellular Differentiation
Normal cells differentiate during
development (becomes specialized
in structure and function). The
more highly differentiated a cell,
the less frequently it will go
through the cell cycle to reproduce
and divide. (Neural cells, which do not
reproduce, are highly differentiated cells).
Cells that seldom or never go
through the cell cycle are unlikely
to become cancerous, while cells
that go through the cell cycle
frequently are more likely to
become so.
C. The Cell Clock
Reproduce occurs in a predictable
number of times, then stops.
This system is important because
if cells divided indefinitely we
would have many more cells than
is compatible with life.
Pathophysiologic Concepts
Uncontrolled Cellular
Reproduction
Cancer cells go through the cycle
more often than normal, causing
accumulation of abnormal cells
(short interphase) .
The cells become independent of
normal growth control signals
(autonomy), so do not respond to
growth inhibitors released by
neighboring cells or inhibitory
growth factors and hormones
traveling in the circulation.
Anaplasia
Anaplasia refers to regression of a
differentiated cell to a less
differentiated stage. Cancer cells
demonstrate various degrees of
anaplasia. By undergoing
anaplasia, a cancer cell loses its
ability to perform its previous
functions and bears little
resemblance to its tissue of origin.
Highly anaplastic cells may
appear embryonic and begin to
express functions of a different
cellular type. Some cancer cells
may become ectopic sites of
hormone production. For instance,
antidiuretic hormone (ADH) or
adrenocorticotrophic hormone
(ACTH).
Tumor Cell Markers
Some cancer cells release tumor
cell markers, which are specific
substances into the blood, urine, or
spinal fluid. Tumor cell markers
may be specific antigens present
on the cancer cells. Some tumor
antigens are similar to fetal
antigens and are called oncofetal
antigens. Because fetal antigens
often do not provoke an immune
response, they may mask the
tumor against the host's immune
system.
Clinical Implications of Tumor
Cell Markers
Tumor cell markers are clinically
important because they offer a
means of identifying certain
cancers as well as a cancer's
progression before, during, and
after treatment. For instance, if a
specific tumor cell marker is
identified in a patient, it suggests
that cancer may exist in the
person, and further diagnostic
evaluation is necessary.
Furthermore, in patients with a
known malignancy, if after
radiation or chemotherapy the
tumor cell marker is not
detectable, it suggests that the
cancer is in remission. If, however,
the tumor cell marker fails to
decrease during therapy or
reappears in high concentration
after therapy, the tumor is unlikely
to be in remission.
Examples of Tumor Cell Markers
Alpha-fetoprotein for liver
,ovarian and testicular cancers
Carcinoembryonic antigen for
colorectal cancer
Human chorionic gonadotropin
(hCG) for many tumors, including
usually cancer of the uterus
Acid phosphatase and prostatespecific antigen (PSA) for prostate
cancer
CA-125, a protein released from
female reproductive organs as well





as from the lining of the chest and
peritoneal cavities. It increases
with inflamed or injured tissue and
is a marker for ovarian cancer.
N.B., Failure to detect a tumor cell
marker does not mean that an
individual is cancer-free.
Tumor Growth Rate
Important characteristics that affect
a tumor's growth rate include the
person's age, sex, and overall health
and nutritional status. The status of
the host's immune system is also
important. An individual who is
immune-suppressed may be unable
to recognize a tumor as foreign.
Certain hormonal states (e.g.,
pregnancy) may stimulate certain
tumor growth rates, while stress may
affect the host's ability to restrict the
development or growth of a tumor.
Important characteristics of a
tumor that affect its growth rate
include its location in the body and
its blood supply.
The degree of cellular anaplasia
and the presence or absence of
tumor growth factors are also
important.
Descriptions of Tumor Growth
and Spread
Growth and spread of a tumor is
often described clinically. Tumor
treatment often depends on the
grade and stage of the cancer.
Grading: An assessment of the
tumor based on the degree of
anaplasia it demonstrates. For

example, poorly differentiated
(highly anaplastic) cells are
assigned a high grade.
Staging: A clinical decision
concerning the size of a tumor, the
degree of local invasion, and the
degree to which it has spread to
distant sites in a given individual.

Local Growth of a Tumor
Growing tumors injure and kill
neighboring cells both by
compressing the cells and blocking
off their blood supply. Tumor cells
also appear to release chemicals or
enzymes that cause the
neighboring cells to lyse and die.
When neighboring cells die, the
tumor can easily grow to occupy
that space. To grow beyond a
certain size, tumors must stimulate
the development of their own
blood supply( angiogenesis) to
meet high metabolic demands.
Metastasis
Metastasis is the movement of
cancer cells from one part of the
body to another. Metastasis
usually occurs through the spread
of cancer cells from the original
(primary) site in the blood or
lymph to a new, secondary site.
The term malignancy refers to the
ability of a tumor to metastasize.
Process of Metastasis
Steps involved in the metastasis of
a primary tumor to a distant site
include :
1-Detachment
To metastasize, cancer cells must
first detach from their primary
cluster. Normal cells detach with
difficulty and if it has become
detached from its neighbors, it
undergoes apoptosis. Cancer cells,
in contrast, easily lose adhesion
with like cells and begin to enter
the circulation.
2- Invasion
To spread to distant sites, detached
tumor cells must gain entrance to a
blood or lymph vessel by secreting
specific enzymes that attack the
integrity of the tissue.
3-Dissemination and Seeding
Movement of tumor cells in the
blood or lymph is called
dissemination. Some tumor cells
will get caught in a capillary or
lymph network downstream from
the primary site. Although many
cells may die, a few tumor cells at
this new site may survive and
begin to seed the area. The more
cells that detach from the primary
tumor, the more likely it is that at
least one will survive the journey
and start a new tumor growth
elsewhere.
When the secondary site has
reached a critical size, the tumor
cells will again begin to produce
tumor angiogenesis factor and new
blood vessel formation will be
initiated to support growth of this
secondary site.
Progress of a Metastasizing Tumor
Because cancer cells tend to be
large, most lodge in the nearest
lymph or capillary bed
downstream from the primary
tumor site. Because of this, the
lungs, which receive systemic
venous blood directly from most
organs, are the most common sites
of metastasis. Venous blood from
the gastrointestinal (GI) tract and
pancreas travels first to the liver
which is the most common site of
cancers from these organs.
N. B., Metastasis is evaluated by
observing for secondary sites in
the lymph nodes nearest to the
primary site, and then
progressively further from this
site. Exceptions to this rule are
tumor cells that show a striking
preference to colonize certain
tissues not necessarily
downstream. The classic example
of this preference is the tendency
of prostate cancer to metastasize
to bone.
The Immune System and Cancer
The presence in the blood of
antibodies, T cells, and natural
killer (NK) cells produced against
specific tumor antigens has been
confirmed in individuals with
cancer. In addition, individuals
who are immunocompromised,
including those with AIDS or
those taking immunosuppressant
drugs, have an increased chance of
developing cancer. All of these
findings demonstrate clearly that
the immune and inflammatory
systems have important roles in
fighting and preventing cancer.
Categories of Cancer
The suffix oma is usually added to
the tissue term to identify it as a
tumor, either benign or cancerous.
Carcinoma is a cancer of the
epithelial tissue, including cells of
the skin, testis, ovary, mucussecreting glands, melaninsecreting cells, breast, cervix,
colon, rectum, stomach, pancreas,
and esophagus.
Lymphoma is a cancer of the
lymphatic tissue, including the
lymph capillarie, spleen, various
lymph nodes, and lymph vessels.
Sarcoma is a cancer of the
connective tissue, including cells
found in the muscle and bone.
Glioma is a cancer of the glial
(support) cells of the central
nervous system.
Carcinoma in situ is a term used to
describe abnormal epithelial cells
that are as yet confined to a certain
area and thus considered
preinvasive lesions.
The Theory of Carcinogenesis
Cancer development is a multi-step
process that usually requires
decades to occur. The first step in
carcinogenesis is thought to be a
mutation in the DNA during DNA
replication (copying). Although
mistakes in DNA copying are not
unusual, most mistakes are
identified by proofreading
enzymes that travel down the
DNA strands to check for errors,
signaling the cell cycle to stop for
repair when necessary. If a mistake
cannot be repaired, the cell
normally is instructed to selfdestruct.
The theory of carcinogenesis
suggests that in certain individuals,
an error in DNA copying may not
be noticed, the cell cycle may not
stop in time for repair, or the
defective cell may not selfdestruct. If the DNA error is not
identified and corrected, the
genetic change becomes a
permanent mutation and is passed
on to all daughter cells. This step is
irreversible and is called cellular
initiation. For a cancer to develop
from this first, irreversible event,
years of additional interactions
with the cell by endogenous
(internally-produced) and
exogenous (environmental) factors
that cause additional genetic
changes must occur, and all must
lead to the production of a cell that
proliferates aggressively and
without quality control. These
additive effects are called
promoting events. Factors that
promote the acceleration of the
cell cycle and those that allow an
abnormal cell to avoid detection
by the immune system are most
likely to result in a mutated cell
becoming carcinogenic.
Promoters of DNA Replication
Errors
- Certain physical agents and
chemicals agents as ionizing
radiation, ultraviolet radiation,
components of cigarette smoke,
aromatic hydrocarbons, certain
dyes, nitrosamines (present in
preserved meats), and asbestos.
- Certain viruses have been
identified that can cause DNA
mutations as Burkitt's lymphoma,
caused by the Epstein-Barr virus,
cervical cancer, caused by certain
strains of the human papilloma
virus, and liver cancer, caused by
the hepatitis B virus. Kaposi's
sarcoma occurs especially in those
suffering from AIDS.
Risk Factors for cancer
Risk factors include exposure to
any physical, chemical, or viral
substance that is known to be
mutagenic, and prolonged
exposure to any promoter.
Mutagens may be inhaled or eaten,
or may act on the skin, such as in
the case of ultraviolet (UV)
radiation.
-Behavioral Risk Factors
Behavioral risk factors include
cigarette smoking and diets rich in
animal fat and preserved meats.
Approximately a third of all
cancers in the United States can be
attributed to cigarette smoking,
and a third to diet. Other
environmental factors, include
exposure to asbestos, coal tar and
radiation from sunlight.
Other behavioral risk factors
include those associated with
sexual behavior.
- Hormonal Risk Factors
- Estrogen may act as a promoter
for certain cancers, such as breast
and endometrial cancer. Because
estrogen levels are high in
menstruating women, the risk for
developing breast cancer is
increased in women who started
menstruating early and reached
menopause late.
- Delayed childbearing or choosing
not to bear children increases the
risk of breast cancer
- Inherited Risk Factors
Certain cancers have a higher
tendency to run in families than
others. For example, colon and
breast cancer .
Factors That are Protective
Against Cancer Development
- Women who breastfeed for at
least 6 consecutive months and
who have had multiple
pregnancies have a reduced risk of
breast cancer.
These findings may relate to the
decreased number of menstrual
periods experienced by these
women.
- Progesterone appears to be
protective against breast cancer by
inhibiting the stimulatory effects
of estrogen. Progesterone is high
during pregnancy, which may
explain why women who have had
many pregnancies have a reduced
risk of breast cancer.
- Dietary factors are important in
reducing cancer risk. These
substances include vitamins A, E,
and C and folic acid, all of which
are prevalent in green, leafy and
colorful vegetables and fruits.
Clinical Manifestations of cancer
Cachexia is a term used to
describe the general wasting of fat
and protein seen in many patients
with cancer.

Anemia occurs for many
different reasons and in many
different types of cancers.
Fatigue frequently occurs as a
result of poor nutrition, protein
malnutrition, and poor
oxygenation of tissues resulting
from anemia..


Diagnostic Tools
Diagnosis of cancer involves
reviewing the patient's clinical
presentation, gaining information

on personal habits such as
smoking .
Screening tests, such as Pap
smears to detect cervical cancer,
mammograms to detect breast
cancer, and digital examinations of
the prostate coupled with a blood
assay for prostate-specific antigen
(PSA). Testing for other cancer
markers may be performed based
on suspicion.
Advanced methods include
radiographs, CAT scans, and


magnetic resonance imaging
(MRI). Special bone scans may
also be used.
Cancer diagnosis is confirmed
by surgically extracting a sample
from a suspicious lesion, a
procedure known as a biopsy, and
performing a microscopic
examination of the cells.

Complications
- Infections develop as a result of
protein malnutrition, other dietary
deficiencies, and immune
suppression .
- Pain may occur as a result of the
invading tumor pressing on nerves
or blood vessels specially in spacelimiting compartments, such as
bone or brain in the area.
Compression of the blood vessels
can lead to tissue hypoxia, lactic
acid accumulation, or cell
death.Headache is a common
manifestation of advanced brain
cancer, and bone pain is common
with bone cancer at any age. GI
pain occurs when the smooth
muscle of the gut is stretched.
Treatment
- Surgery has a better chance of
curing a cancer if used on solid,
well-circumscribed tumors.
Tumors that have metastasized
may be treated with surgery to
give the patient relief from pain.
Surgery is also used to debulk the
tumor, which reduces burden and
improves the response to
chemotherapy or radiotherapy.
- Radiation therapy uses ionizing
radiation to kill cells primarily by
altering the DNA enough that
brakes on the cell cycle. Often,
radiation is used in addition to
surgery to shrink the tumor.
Cancer
Therapy
Surgery
Mode
of
Action
Reduc
e
Adver
se
Effect
s
Pain;
defor
tumor
size to
allevia
te
pain;
preven
t
metast
asis if
used
early;
diagno
sis
mity
Radiation
Dama
ge
dividi
ng
cells;
stimul
ate
apopto
sis;
halt
cell
cycle
Injure
s and
leads
to
death
of
norma
l cells;
bone
marro
w
depres
sion;
Chemotherap
y
Multip
le
action
s on
cells
to stop
progre
ssion
throug
skin
desqu
amati
on
Injure
s and
kills
norma
l cells;
anore
xia;
nause
a;
h cell
cycle;
may
involv
e
combi
nation
therap
y and
may
act
selecti
vely
bone
marro
w
depres
sion
Immunothera
py/Biotherapy
or
nonsel
ectivel
y
Activa
te host
immu
ne
syste
m to
better
recogn
ize
Some
drugs
may
cause
flulike
sympt
oms
and
destro
y
tumor
cells;
specifi
cally
block
enzym
es and
growt
h
factors
requir
ed for
metast
asis;
Chemotherapy uses drugs of
several different classes to destroy
tumors which grow rapidly and
therefore are most susceptible to
chemotherapy. However, healthy
cells are also susceptible to the
damaging effects of chemotherapy.
Chemotherapy is frequently used in
addition to surgery or radiation

therapy, but may be used alone. It
also may be used for palliative
purposes. Chemotherapy usually
causes bone marrow suppression,
which in turn causes fatigue, anemia,
bleeding tendencies, and an
increased risk of infection.
Immunotherapy is a form of
cancer treatment that takes
advantage of the two cardinal
features of the immune system:
specificity and memory.
Immunotherapy may be used to

identify a tumor and any sites of
hidden metastasis. Immunotherapy
may stimulate the host's own
immune system to respond more
aggressively to a tumor, or tumor
cells may be attacked by
antibodies developed in the
laboratory.
Cancer Prevention
- Avoidance of cigarette smoking
- A diet rich in fruits, vegetables,
and fiber and low in animal fat .
- Avoidance of sexually
transmitted diseases
Cancer Detection
- Early cancer detection tests
include self breast examination
and mammography, prostate
examination, self testicular
examination, and regular skin
examination.
- Some screening tests, including
Pap smears, tests for intestinal
polyps, and biopsies of abnormal
skin lesions.