Fundamentals of Cancer Detection, Treatment, and Prevention. Surya K. DeЧитать онлайн книгу.
Chromosomes are found in all living cells and consist of a single molecule of DNA bound to various proteins (Figure 1.3). They carry the genes, which are the basic units determining inherited traits. Genes control cell function, particularly how cells grow and divide, and when they need to stop this growth [5–14].
Figure 1.3 Cell structure showing DNA in the nucleus. The DNA molecule is a double helix. A gene is a length of DNA that codes for the manufacture of a specific protein.
In the human body, there are 46 chromosomes, arranged in 2 sets of 23. We inherit one set from our mother and one from our father. Chromosomes contain all the information for the physical characteristics that make up an individual. One chromosome in each set determines whether a person is female or male. The other 22 chromosome pairs decide other physical characteristics in the human body. These chromosome pairs are also called autosomes.
Genes regulate protein production. Each protein functions on its own and also carries messages for the cell. Each gene follows specific instructions, encoded in their genetic material, for producing proteins; each protein performs specific functions for the cell (Figure 1.4).
Figure 1.4 Information from DNA is used to make proteins from genes.
Cancers start when one or more genes mutate. Mutations, however, are a normal occurrence. Their results may be beneficial, harmful, or neutral, depending on the location within the gene where the change has taken place. Most of the time the body corrects the mutations and nothing unusual happens.
A single mutation will generally not produce cancer. Typically, cancer develops from multiple mutations over a lifetime, which is why cancer occurs more frequently in older people. Mutations have had more opportunities to occur the longer a person lives. Mutation of genetic material changes the instructions for protein formation, resulting in the production of an abnormal protein or sometimes prevention of a certain protein being formed. An abnormal protein cannot carry out its specific function correctly, possibly leading to uncontrolled cell multiplication and the start of cancer (Figure 1.5).
Figure 1.5 Cancer cells start as normal cells, which acquire mutations over time that change them to cancer cells.
1.6 Genetic Mutations
There are two basic types of genetic mutations:
1.6.1 Acquired Mutations
Mutations of this type are the most common cause of cancer, and when this occurs, it is called sporadic cancer. These mutations, initially affecting only a few cells in the body, damage the genes in these cells. Since these mutations are acquired, they do not pass from parents to children. Major factors contributing to acquired mutations include:
Tobacco
Ultraviolet (UV) radiation
Viruses
Age
1.6.2 Germline Mutations
Not as common as acquired mutations, germline mutations take place in reproductive cells, such as those in a female's egg or a male's sperm. Offspring resulting from the union of reproductive cells with germline mutation receive that mutation, which is copied into every cell in the body as it develops. Since these mutations are in the reproductive cells, they are carried from generation to generation and are known as inherited cancers. Germline cancers comprise between 5 and 20% of all cancers.
Germline cancers should not be confused, however, with germ cell tumors, which start in the cells that give rise to sperm or eggs. These tumors can develop almost anywhere in the body, and they can be either benign or malignant.
1.7 Genes Connected to Cancer
Certain types of genes have been linked to the development of cancer in the human body. Scientists categorize these genes in broad groups:
1.7.1 Tumor Suppressor Genes
The genes have the protective feature of controlling cell growth by:
Monitoring new cell divisions
Correcting DNA sequences that have mutated
Controlling cell death (apoptosis)
Examples include TP53 (tumor protein 53 or cellular tumor antigen p53, or referred to as p53), PTEN, RB1, and APC. When tumor suppressor genes mutate, cell growth is unchecked and may result in tumor formation.
In the case of germline mutations, if certain tumor suppressor genes – namely BRCA1 or BRCA2 – mutate, there is a higher chance of developing hereditary breast or ovarian cancer for women, and prostate cancer for men. These specific mutations also have been linked to an increased risk of pancreatic cancer and melanoma.
More than half of diagnosed cancers are caused by mutations that damage or disable gene p53 (Figure 1.6). This is a common acquired mutation. Much more rarely, germline p53 mutations occur with subsequent greater risk for many types of cancer in family members.
Figure 1.6 Structure of p53 tumor suppressor protein. p53 prevents cancer formation and acts as a guardian of the genome. Mutations in the p53 gene contribute to about half of the cases of human cancer.
Source: Juan Gärtner/Adobe Stock
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1.7.2 Oncogenes
These genes change healthy cells into cancerous ones with acquired mutations. Examples of common oncogenes include HER2 (human epidermal growth factor receptor 2) and genes in the RAS family. HER2 is a specialized protein found in certain cancerous cells, including those in the breast and ovaries, where it oversees the growth and spreading of the disease. Another family of genes, referred to as RAS, manufactures proteins that interfere with cell communication pathways, as well as cells' growth and death.
1.7.3 DNA Repair Genes
These genes take care of mistakes that occur