**2. Molecular basis of carcinogenesis in colorectal cancer**

In medical practice, patients with cancer present with great frequency, clinical evolution in a differentiated way in response to the treatment performed. As a result, there is a high margin of uncertainty as to the effectuation of the treatment performed, not infrequently counting initially favorable prognostic evaluations [3].

Cancer results from a long process of at least three phases: initiation, promotion and progression, which reflect accumulated genetic alterations, responsible for the transformation of normal cells into neoplastic cells. The mechanisms of transformation of a normal cell into neoplastic involve a number of genetic and molecular events that affect proliferation and differentiation. In the pathogenesis of neoplastic processes, two groups of genes are involved: proto-oncogenes, which stimulate cell growth and impede differentiation, and tumor suppressor genes, which promote differentiation and limit cell proliferation. The imbalance in the regulation of this system, through the activation of proto-oncogenes or loss of the function of tumor suppressor genes, can lead to the uncontrolled proliferation of cells and to the accumulation of successive genetic abnormalities characteristic of neoplastic cells [4–7].

The development of cancer (oncogenesis) results from mutations in one or more genes, responsible for the regulation of cell growth and programmed cell death called apoptosis (**Figure 1**) [8]. When cancer occurs as part of a hereditary cancer syndrome, the initial mutation causing the cancer is inherited through germ lineage. However, most cancers are sporadic because mutations occur in a single somatic cell, which then divides and proceeds to develop cancer [9].

Considering a frequency of 10-10 replication errors per DNA basis, cell division, and about 1015 cell divisions over the life span of an adult, only replication errors would result in thousands of mutations in the DNA of the genome [8].

Once initiated, a cancer progresses through additional accumulation of genetic damage through mutations in maintenance genes, which encode the DNA repairing cellular machinery. Changes in these genes produce mutations in increasing numbers, leading to failures in controlling cell proliferation and repairing DNA damage. In this way, the original clone of neoplastic cells functions as a reservoir of genetically unstable cells, known as cancer stem cells. These give rise to multiple

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**Figure 3.**

*A Genetic Perspective on Colorectal Cancer Progression DOI: http://dx.doi.org/10.5772/intechopen.85894*

by Hill et al. (**Figure 3**) [12].

*shown as −. Modified from Thompson and Thompson [8].*

**Figure 1.**

**Figure 2.**

underlining of varying degrees of malignancy, each carrying a set of mutations. In this context, cancer is a multifactorial disease with an important genetic component, and mutations are central to its etiology and progression [8] (**Figure 2**). The classical CCR carcinogenesis model is based on the adenoma-carcinoma sequence in which tumor onset occurs from a sequential and progressive process. This involves the activation of oncogenesis (K-ras) and the inactivation of tumor suppressor genes (APC, DCC, p53) [10, 11]. This model of carcinogenesis, where there is chromosomal instability, is usually found in the distal segments of the colon and rectum [11]. The adenoma-carcinoma sequence was described for the first time

*Mechanism of oncogenesis. General scheme for mechanism of oncogenesis by proto-oncogene activation, loss of tumor suppressor gene expression, activation of anti-apoptotic genes or loss of pro-apoptotic gene expression. The effect of the genes that induce a process is shown as +, while the effect of the genes that suppress a process is* 

*Stages in the evolution of cancer. Increasing degrees of abnormalities are associated with sequential loss of tumor suppressor genes from various chromosomes and activation of proto-oncogenes, with or without a defect,* 

*The adenoma-carcinoma sequence. Postulated mechanism for progression from normal tissue to adenoma to carcinoma. n: normal gene; p: adenoma gene (recessive), so that cell pp: is adenoma-prone. A: environmental agent causing adenomas only in adenoma-prone cell. B: environmental agent causing adenomas to grow.* 

*C: agent causing adenomas to develop into carcinomas. Modified from Hill et al. [12].*

*concomitant in DNA repair. Modified from Thompson and Thompson [8].*
