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Unit 3
Applying concepts from the nursing process
Aetiology
Categories of agents or factors implicated in carcinogenesis
include viruses and bacteria, physical agents, chemical agents,
genetic or familial factors, dietary factors and hormonal agents.
Viruses and bacteria
Viruses as a cause of human cancers are hard to determine
because viruses are difficult to isolate. Infectious causes are
considered or suspected, however, when specific cancers
appear in clusters. Viruses are thought to incorporate them-
selves in the genetic structure of cells, thus altering future gen-
erations of that cell population—perhaps leading to a cancer.
For example, the Epstein-Barr virus is highly suspect as a cause
in Burkitt’s lymphoma, nasopharyngeal cancers, and some
types of non-Hodgkin’s lymphoma and Hodgkin’s disease.
Herpes simplex virus type II, cytomegalovirus, and human
papilloma virus types 16, 18, 31 and 33 are associated with dys-
plasia and cancer of the cervix. The hepatitis B virus is impli-
cated in cancer of the liver; the human T-cell lymphotropic
virus may be a cause of some lymphocytic leukaemias and
lymphomas; and the human immunodeficiency virus (HIV) is
associated with Kaposi’s sarcoma. The bacterium
Helicobacter
pylori
has been associated with an increased incidence of
gastric malignancy, perhaps secondary to inflammation and
injury of gastric cells.
Bacteria have been evaluated as a cause of cancer over
the years but with little evidence to support the link of
bacteria to cancer. Chronic inflammatory reactions to bacteria
and the production of carcinogenic metabolites are possible
mechanisms under investigation. In the early 1990s, the
International Agency for Research on Cancer (IARC) iden-
tified
Helicobacter pylori
(
H. pylori
) as the first bacterium to be
termed a definite cause of cancer in humans.
H. pylori
has been
associated with an increased incidence of gastric malignancy
related to chronic superficial gastritis, with resultant atrophic
and metaplastic changes to the gastric mucosa (Schottenfeld &
Beebe-Dimmer, 2006).
Physical agents
Physical factors associated with carcinogenesis include
exposure to sunlight or radiation, chronic irritation or inflam-
mation and tobacco use.
Excessive exposure to the ultraviolet rays of the sun, espe-
cially in fair-skinned, blue- or green-eyed people, increases the
risk for skin cancers. Factors such as clothing styles (sleeveless
shirts or shorts), use of sunscreens, occupation, recreational
habits and environmental variables, including humidity,
altitude and latitude, all play a role in the amount of exposure
to ultraviolet light.
Exposure to ionising radiation can occur with repeated
diagnostic x-ray procedures or with radiation therapy used to
treat disease. Fortunately, improved x-ray equipment appro-
priately minimises the risk for extensive radiation exposure.
Radiation therapy used in disease treatment or exposure to
radioactive materials at nuclear weapon manufacturing sites or
nuclear power plants is associated with a higher incidence of
leukaemias, multiple myeloma, and cancers of the lung, bone,
breast, thyroid and other tissues. Background radiation from
the natural decay processes that produce radon has also been
associated with lung cancer. Homes with high levels of trapped
radon should be ventilated to allow the gas to disperse into the
atmosphere.
rapidly stimulate formation of new blood vessels, which helps
malignant cells obtain the necessary nutrients and oxygen. It is
also through this vascular network that tumour emboli can
enter the systemic circulation and travel to distant sites. Large
tumour emboli that become trapped in the microcirculation of
distant sites may further metastasise to other sites. Therapies
that target VEGF or its receptors are being used to treat many
cancers effectively (see Targeted therapies discussed later in
this chapter).
Carcinogenesis
Molecular process
Malignant transformation, or
carcinogenesis
, is thought to be
at least a three-step cellular process: initiation, promotion and
progression. Agents that initiate or promote cellular transfor-
mation are referred to as carcinogens.
In
initiation,
the first step, initiators (carcinogens), such
as chemicals, physical factors and biological agents, escape
normal enzymatic mechanisms and alter the genetic struc-
ture of the cellular DNA. Normally, these alterations are
reversed by DNA repair mechanisms or the changes initiate
programmed cellular suicide (apoptosis). Occasionally, cells
escape these protective mechanisms and permanent cellular
mutations occur. These mutations usually are not significant
to cells until the second step of carcinogenesis.
During
promotion,
repeated exposure to promoting agents
(co-carcinogens) causes the expression of abnormal or mutant
genetic information even after long latency periods. Latency
periods for the promotion of cellular mutations vary with the
type of agent and the dosage of the promoter as well as the
innate characteristics of the target cell.
Cellular oncogenes, present in all mammalian systems,
are responsible for the vital cellular functions of growth and
differentiation. Cellular proto-oncogenes are present in cells
and act as an ‘on switch’ for cellular growth. Proto-oncogenes
are influenced by multiple growth factors that stimulate cell
proliferation, such as epidermal growth factor (EGF) and
transforming growth factor alpha. Another proto-oncogene
that plays an important role in cancer development is the
k-ras
(KRAS2)
oncogene located on chromosome 12.
Similarly, cancer suppressor genes ‘turn off’ or regulate
unneeded cellular proliferation. When the suppressor genes
become mutated, rearranged or amplified or lose their regula-
tory capabilities, malignant cells are allowed to reproduce. The
p53 (TP53)
gene is a tumour suppressor gene that is frequently
mutated in many human cancers. This gene regulates whether
cells will repair or die after DNA damage.
Apoptosis
is the
innate cellular process of programmed cell death. Alterations
in
TP53
may decrease apoptotic signals, thus giving rise to a
survival advantage for mutant cell populations. Mutant
TP53
gene is associated with a poor prognosis and may be associated
with determining response to treatment. Once this genetic
expression occurs in cells, the cells begin to produce mutant
cell populations that are different from their original cellular
ancestors.
Progression
is the third step of cellular carcinogenesis. The
cellular changes formed during initiation and promotion now
exhibit increased malignant behaviour. These cells now show
a propensity to invade adjacent tissues and to metastasise.
Agents that initiate or promote cellular transformation are
referred to as carcinogens.
