Some fundamental principles of the genetic basis of cancer show us the significance of genes in the formation and mutation in cancers.
3.2.1. Nonlethal genetic damage lies at the heart of carcinogenesis. Such genetic damage (or mutation) may be acquired by the action of environmental agents, such as chemicals, radiation, or viruses, or it may be inherited in the germ line. The genetic hypothesis of cancer implies that a tumor mass results from the clonal expansion of a single progenitor cell that has incurred the genetic damage (i.e., tumors are monoclonal). This expectation has been realized in most tumors that have been analyzed. Clonality of tumors is assessed quite readily in women who are heterozygous for polymorphic x-linked markers, such as the enzyme glucose-6-phosphate dehydrogenase (g6pd) or x-linked restriction fragment length polymorphisms.
3.2.2. Three classes of normal regulatory genes – the growth-promoting proto-oncogenes, the growth-inhibiting cancer-suppressor genes (anti-oncogenes), and genes that regulate programmed cell death, or apoptosis – are the principal targets of genetic damage. Mutant alleles of proto-oncogenes are considered dominant because they transform cells despite the presence of their normal counterpart. In contrast, both normal alleles of the tumor-suppressor genes must be damaged for transformation to occur, so this family of genes is sometimes referred to as recessive oncogenes. Genes that regulate apoptosis may be dominant, as are proto-oncogenes, or they may behave as cancer-suppressor genes.
3.2.3. In addition to the three classes of genes mentioned earlier, a fourth category of genes, those that regulate repair of damaged DNA, is also pertinent in carcinogenesis. The DNA repair genes affect cell proliferation or survival indirectly by influencing the ability of the organism to repair nonlethal damage in other genes, including proto-oncogene, tumor-suppressor genes, and genes that regulate apoptosis. A disability in the DNA repair genes can predispose to mutations in the genome and hence to neoplastic transformation. Both alleles of DNA repair genes must be inactivated to induce such genomic instability; in this sense, DNA repair genes may also be considered as tumor-suppressor genes.
3.2.4. Carcinogenesis is a multistep process at both the phenotypic and the genetic levels. A malignant neoplasm has several phenotypic attributes, such as excessive growth, local invasiveness, and the ability to form distant metastases. These characteristics are acquired in a stepwise fashion, a phenomenon called tumor progression. At the molecular level, progression results from accumulation of genetic lesions that in some instances are favored by defects in DNA repair.
Thus we come to know that genes are the responsible factors for the formation of any type of cancer and also that a mutation in a single cell can bring about a formation into cancer and a change in the genotype of the genetic constitution or DNA coding is the basic responsible factor in the formation of cancer.
Thus when a cell crosses its limit of tolerance of handling a stress, it becomes unstable and can undergo mutation. If the pathology of a cell is reversible and a medicine is administered, then relief and cure can take place. This means the modifications taken place in a cell can be reversed. But if the irritation caused due to the stress is still persistent and the cell crosses its tolerance and the modification which has occurred in the cell gets permanent and irreversible and the mutation is permanent and is the trigger for cancer and Neoplasia.