IV.

How Cancer Occurs

Cancer is a multi-stage process where a series of irreversible genetic errors occur in a cell in the body during a patient’s lifetime. The early stages (initiation) are critical for setting the process off. Later changes lead to spread and increased growth rate, and are triggered by a range of external factors, known as promoters. These errors may happen because the person has been exposed to cancer-causing agents (carcinogens). For instance, cigarette smoke contains many chemical initiators and promoters.

A.

Gene Defects

In some people, however, there are also inherited gene defects that can give a potential cancerous cell a head start. Genes are made of deoxyribonulceic acid (DNA—the cell’s chemical “instruction manual”—see Nucleic Acids) and are found in the centre of the cell in structures known as chromosomes. Humans have 23 pairs of chromosomes and over 50,000 genes. If a chromosome is likened to a book, each gene is a paragraph; a fault in a gene may be likened to a misprint.

Every time a cell divides a copy is made of the DNA. Sometimes an error occurs and a new cell ends up with an altered gene—a mutation. If the mutation occurs in a gene that normally controls cell growth, that cell may acquire the potential to become a cancer cell.

A cancerous growth, or neoplasm, is therefore clonal—that is, all its cells are descendants of a single cell. These cells have escaped the control of the normal forces regulating cellular growth. Resembling embryonic cells, they are unable to differentiate or mature into an adult, functioning state. As these cells multiply, they may form a mass known as a tumour, which enlarges and continues to grow without regard to the function of the tissue of origin.

The body has ways of fighting back against mutations and a number of faults has to accumulate before a tumour develops. This can take a long time, which is why cancer is mainly a disease of older people; for instance, 95 per cent of bowel cancers occur in those over 50.

B.

Tumours

Almost all cancers form tumours, but not all tumours are cancerous, or malignant; the greatest number are benign (not threatening to health). Benign tumours are characterized by entirely localized growth and are usually separated from neighbouring tissue by a surrounding capsule. Benign tumours generally grow slowly, and in structure closely resemble the tissue of origin. In some instances they may endanger the patient by obstructing, compressing, or displacing neighbouring structures, as in the brain. A few benign tumours, such as polyps of the colon, may be precancerous.

C.

Invasion and Spreading

The most significant attribute of malignant tumours is their ability to spread beyond the site of origin. Cancer may invade neighbouring tissues by direct extension or infiltration, or it may disseminate to distant sites, forming secondary growths known as metastases. The routes and sites of metastases vary with different primary cancers:

(1) When a cancer extends through the surface of the organ of origin into a cavity, cells may break away from the surface and become implanted on the surface of adjacent organs.

(2) Tumour cells may migrate into the lymphatic channels and be carried to the draining lymph nodes, or they may penetrate the blood vessels. Once in the bloodstream, the tumour cells are carried to the point at which the vessels become too small for the large tumour cells to pass. Cells from tumours of the gastrointestinal tract will be stopped in the liver. Later they may go on to the lungs. Cells from all other tumours will go to the lungs before being carried to other organs. The lungs and liver are therefore common sites of metastases.

(3) Many cancers tend to shed cells into the bloodstream early in their course. Most of these cells die in the bloodstream, but some lodge against the surface and penetrate the wall into the tissue. A few may find themselves in a favourable tissue in which they are able to survive and grow into a tumour. Others may divide only a few times, forming a small nest of cells that then remain dormant (a micrometastasis). They may remain dormant for many years, only to begin to grow again as recurrent cancer, for reasons unknown.

Cancer cells, even when widely disseminated, may retain the physical and biological characteristics of their tissue of origin. Thus, a pathologist can often determine the site of origin of metastatic tumours by microscopic examination of the cancerous tissue. Identification of tumours of the endocrine glands, for example, is simplified because they may produce excessive amounts of the hormone that is produced by the parent tissue. Such tumours may also respond to administration of the hormones that normally control that tissue.

In general, the less closely a cancer resembles its tissue of origin, the more malignant and rapidly invasive it tends to be; however, the rate of growth of a cancer depends not only on cellular type and the degree of differentiation from the tissue of origin, but also on various host factors. A characteristic of malignancy is tumour-cell heterogeneity. Because of the abnormalities of proliferation in tumour cells, they are more susceptible to mutation. With time, a tumour tends to become less differentiated and to grow more rapidly. It may also develop increased resistance to chemotherapy or radiotherapy.