However, it should be noted that the clonal derivation of tumors does not always indicate that the initial

progenitor cell, responsible for the formation of the tumor, has originally acquired all the defining features of a
cancerous cell. Contrarily, the progression of cancer involves a complex sequence of changes in cells, leading to
their eventual transformation into a malignant state. An evidence of the multistep progression of cancer is the
predominant occurrence of cancer in individuals throughout the latter stages of their lives. The prevalence of
colon cancer exhibits a notable rise of over ten times from the age of 30 to 50, followed by an additional tenfold
increase from 50 to 70 years of age (Figure 15.3). The notable rise in cancer occurrence with advancing age
implies that the majority of malignancies arise due to the accumulation of various abnormalities over extended
periods of time.

According to Figure 15.3, there is a notable correlation between advancing age and an elevated incidence of
colon cancer.
According to Figure 15.3, there is a positive correlation between age and the incidence of colon cancer,
indicating that the rate of colon cancer tends to increase as individuals get older. The annual mortality rates
attributed to colon cancer within the United States. (Data from J. Cairns, 1978. The book titled "Cancer: Science
and Society" was published in New York by W. H. Freeman.

The cellular level perspective of cancer formation is characterized as a complex series of stages that include
mutation and the subsequent selection of cells with a gradual enhancement in their ability to proliferate, survive,
invade, and metastasize (as seen in Figure 15.4). The first stage of the process, known as tumor initiation, is
hypothesized to arise from a genetic modification that triggers aberrant cellular growth in a solitary cell. The
process of cell proliferation subsequently results in the expansion of a group of tumor cells that are formed from
a single clone. The process of tumor growth continues as other mutations arise within the cellular composition
of the tumor population. Certain mutations provide a cell with a selection advantage, such as enhanced growth
rate. As a result, the progeny of a cell with such a mutation will gain dominance among the tumor population.
The phenomenon under consideration is referred to as clonal selection, since it involves the emergence of a
distinct population of tumor cells that has developed due to its heightened growth rate or other characteristics,
such as enhanced survival, invasion, or metastasis, which provide a selective advantage. The process of clonal
selection persists throughout the progression of tumors, leading to a constant enhancement in their growth rate
and malignancy.

The diagram shown in Figure 15.4 illustrates the several stages involved in the formation of a tumor.
Figure 15.4 illustrates the several stages involved in the formation of a tumor. The onset of cancer occurs when
a solitary mutant cell begins aberrant proliferation. Subsequent mutations, followed by the process of selection
favoring cells with higher growth rates within the population, subsequently lead to the advancement of (more...)

Research conducted on colon carcinomas has shown a distinct illustration of the advancement of tumors in the
course of the formation of a prevalent malignant condition in humans (refer to Figure 15.5). The first phase in
the progression of tumors involves heightened proliferation of colon epithelial cells. It is postulated that a single
cell from this rapidly dividing cell population subsequently becomes a minute, non-malignant tumor, often
referred to as an adenoma or polyp. Subsequent iterations of clonal selection result in the development of
adenomas that exhibit progressive enlargement and enhanced capacity for proliferation. Malignant carcinomas
subsequently emerge from the benign adenomas, as shown by the infiltration of tumor cells beyond the basal
lamina and into the adjacent connective tissue. Subsequently, the cancerous cells undergo further proliferation
and disseminate inside the connective tissues of the colon wall. Ultimately, the neoplastic cells breach the
colonic wall and infiltrate further intra-abdominal organs, such as the bladder or small intestine. Furthermore,
the malignant cells have the ability to infiltrate the circulatory and lymphatic systems, so facilitating their
dissemination and metastasis to many anatomical sites inside the organism.

In Figure 15.5, the progression of colon carcinomas is shown.

In Figure 15.5, the progression of colon carcinomas is shown. The development of a proliferative cell
population, originating from a single originally modified cell, follows a progression from benign adenomas of
escalating dimensions to the formation of malignant carcinoma. Cancer cells have the ability to infiltrate the
underlying connective tissue.

Please refer to the next section for an exploration of the causes of cancer.
Carcinogens, which are substances known to induce cancer, have been found via many research methods,
including studies conducted on experimental animals and epidemiological analyses examining cancer rates
within human populations. For instance, the prevalence of lung cancer among individuals who smoke cigarettes
serves as an example of such findings. Due to the intricate and multifaceted nature of carcinogenesis, the
probability of cancer formation is influenced by several variables. Consequently, it is unduly reductionist to
attribute most malignancies to singular causative agents. However, several factors, including as radiation,
chemicals, and viruses, have been shown to elicit carcinogenic effects in both animal models and human
subjects.

Radiation and other chemical carcinogens are known to exert their effects via the mechanism of DNA damage
and subsequent induction of mutations (Figure 15.6). The term "initiating agents" is often used to describe these
carcinogens, since it is believed that the first occurrence of mutations in crucial target genes is the primary factor
in the progression of cancer. Several factors have been identified as initiating agents that play a role in the
development of human cancers. These include solar ultraviolet radiation, which is considered the primary cause
of skin cancer. Additionally, carcinogenic chemicals found in tobacco smoke have been linked to the
development of various types of cancer. Another initiating agent is aflatoxin, a highly potent liver carcinogen
produced by certain molds that can contaminate inadequately stored supplies of peanuts and other grains. The
primary etiological factors responsible for human cancer have been recognized as the carcinogens present in
tobacco smoke, which include benzo(a)pyrene, dimethylnitrosamine, and nickel compounds. The act of smoking
has been widely acknowledged as the primary factor responsible for around 80 to 90% of lung cancers, in
addition to its association with malignancies affecting other locations such as the oral cavity, pharynx, larynx,
esophagus, and others. The collective data suggests that smoking is accountable for around 33% of all cancer-
related fatalities, which is a substantial impact attributed to a solitary carcinogenic substance.