Epidemiology

Epidemiological studies of the worldwide incidence of cancers have identified striking differences among countries and population groups. For example, the incidence of and death rates for skin cancer are much higher in Australia and New Zealand than in the Scandinavian countries—presumably because of the marked differences between these two regions in total annual hours of exposure to sunlight. The importance of environmental influences is highlighted by comparing the incidence of and death rates for cancers among populations in different geographic regions. For example, prostate and colon cancer rates in Japanese persons living in Japan differ from the rates in Japanese persons who have emigrated to the United States, the rates of their offspring born in California, and the rates of long-term white residents of that state. These rates are much lower among Japanese living in Japan than they are in white Californians. However, the rates for each type of tumour among first-generation Japanese immigrants are intermediate between the rates in Japan and those in California, suggesting that environmental and cultural factors may play a more important role than genetic ones.

The role of genetics

The irreversibility of the structural and behavioral changes of cancer cells has long been recognized and has favoured the postulate that they are probably due to permanent genetic alterations. This postulate remained speculative until the discovery in 1979 that oncogenes (cancer-causing genes) are derived from proto-oncogenes (normal growth-regulatory cellular genes). When proto-oncogenes become mutated or deregulated, they are converted to oncogenes, which are capable of causing the malignant transformation of cells, including those of humans. Cellular proto-oncogenes code for proteins involved in cell regulation, such as growth factors, their receptors, and transmembrane signal transducers. Thus, changes in the structure of proto-oncogenes and their conversion to oncogenes results in the synthesis of abnormal proteins that are incapable of carrying out their usual growth-regulatory functions. In identifying the genes involved in the development of cancer, researchers discovered a group of cellular genes—tumour-suppressor, or suppressor, genes—whose protein products normally negatively regulate cell growth by suppressing cell proliferation, thus counterbalancing the growth-stimulatory effects of proteins synthesized by proto-oncogenes. Genetic analyses of various animal and human cancers have demonstrated that, in the majority, alterations of oncogenes and suppressor genes were often simultaneously present. These analyses suggest that multiple genetic alterations involving growth-stimulatory and growth-inhibitory genes are required for the induction of malignancy. Such discoveries have ushered in a new era in cancer biology and may well lead to the eventual control, cure, and prevention of malignant diseases.

Heredity and environment

The many causes of cancer include intrinsic factors, such as heredity, and extrinsic factors, such as environment and lifestyle. Hereditary causes of cancer are less common and are due to the inheritance of a single mutant gene that greatly increases the risk of developing a malignant tumour. Such cancers include (1) a childhood tumour of the eye, retinoblastoma, and a bone tumour, osteosarcoma, both of which involve the loss of a tumour suppressor gene, and (2) familial adenomatous polyposis, in which all patients develop colon cancer by age 50. The most common types of cancer that occur sporadically, such as cancers of the breast, ovary, colon, and pancreas, also have been documented to occur in familial forms. The children in such families appear to have a two- to threefold increased risk of developing a particular tumour, but the transmission pattern is unclear. A still rarer hereditary cause of cancer is an inherited deficiency in the ability to repair DNA. Patients with this defect (known as xeroderma pigmentosum) are particularly sensitive to sunlight and develop skin cancer during early adolescence because of unrepaired mutations induced by ultraviolet (UV) light.

Although the environment contains many agents that can cause cancer in humans, the extent to which they contribute to the human disease is often difficult to assess. For example, the link between tobacco smoking and lung cancer is clear; however, little is known about the cause of cancer of the prostate, the most common form of cancer in males, despite the fact that many factors—including age, race, male hormone, increased consumption of dietary fat, and a genetic basis—have been implicated.

Three categories of carcinogens (chemical or physical agents that mutate DNA) that induce cancer in experimental animals and humans have been identified in the environment: (1) chemicals, (2) radiant energy, and (3) oncogenic viruses.