The Biology of Cancer - Vibrational Spectroscopy for Tissue Analysis - page 38

system to other areas of the body and establish new tumours. They continue
to grow in new locations. This process, as mentioned before, is referred to as
metastasis [6].
The fact that cancer is predominantly a disease of the elderly, and age is
the most important determinant of cancer risk for both males and females
[10,16], can illustrate the multistep and successive nature of the disease and
the necessity of time for its establishment. Most cancers arise after 65 years
of age [16], and an increasing proportion at age 85 and over [5].
Causes of Cancer
Cancers arise mainly from deregulated proliferation. However, modulation
of the normal processes that leads to cell loss (programmed cell death or apop-
tosis) is also sufficient, although not necessary, for tumour development [30].
Since the development of malignancy is a complex multistep process, many
factors may affect the likelihood that cancer will develop, and it is overly
simplistic to speak of single causes of most cancers. Nonetheless, many
agents, including radiation, chemicals, and viruses, have been found to
induce cancer in both experimental animals and humans. These agents are
called carcinogens [7].
DNA mutation is the well-known explanation for the initiation of any
malignancy, but the cell must also be incited into proliferation [31]. DNA
mutations to facilitate such expansion must occur on one or more genes
affecting cell growth, differentiation, death, and gene replication. DNA
mutations may occur through environmental causes, but are most likely to
occur from internal factors such as endocrine estrogen exposure and errors
in DNA synthesis or replication.
It must be mentioned that in order to initiate any malignancy, such altera-
tions should take place in several genes [32]. For instance, it has been iden-
tified that in esophageal squamous cell carcinoma (ESCC), 147 genes are
up-regulated and 376 are down-regulated [33], or 167 genes have been dem-
onstrated to be significantly overexpressed and strongly related to radio-
resistance of oral squamous cell carcinoma [34]. In addition, the results of
some studies demonstrate the feasibility of prognosis identification using the
altered genes [35-37]. A gene expression signature consisting of 70 genes, for
example, has been identified as strongly predictive of good or poor progno-
sis in breast cancer [38].
Radiation and chemical carcinogens act by damaging DNA and induc-
ing mutations. Some of the carcinogens that contribute to human cancers
include solar ultraviolet radiation (the major cause of skin cancer), carcino-
genic chemicals in tobacco smoke, and aflatoxin (a potent liver carcinogen
produced by some molds that contaminate improperly stored supplies of