Cancer is caused by mutations in genes that control cell division. Some of these genes, called oncogenes, stimulate cell division; others, called tumor suppressor genes, slow this process. In the normal state, both types of genes work together, enabling the body to replace dead cells and repair damaged ones. Mutations in these genes cause cells to proliferate out of control; these cells grow and divide without regard for cell death. The cell cycle is regulated biochemically, and 2 important groups of enzymes are involved in this process: cyclin-dependent kinases (CDKs) and cyclin-dependent phosphatases. (An example of CDK function involves the p53 tumor suppressor gene, which upregulates the p21 inhibitor of CDK function.)
Gene mutations can be inherited or can result from damage to DNA caused by environmental exposures. Cancer causes, therefore, are explained on the basis of chemical, radiation-related, or viral conditions that occur in a complex milieu, including the host’s genetic composition and immunobiologic status. Epidemiologic data suggest that as many as 80% of the cases of cancer in humans may be due to exogenous or environmental chemical exposure. If these chemicals could be properly identified, a major proportion of human cancers could be prevented by reducing host exposure or by protecting the host.
The general population is exposed to both naturally occurring ionizing radiation and man-made ionizing radiation. Man-made sources include medical diagnostic equipment and technologically altered natural sources (such as phosphate fertilizers and building materials containing small amounts of radioactivity). The carcinogenic effects of radiation exposure result from molecular lesions caused by random interactions of radiation with atoms and molecules. Most molecular lesions induced in this way are of little consequence to the affected cell. However, DNA is not repaired with 100% efficiency, and mutations and chromosomal aberrations accrue with increasing radiation doses. Parameters that influence the response of the target tissue include the total radiation dose, the dose rate, the quality of the radiation source, the characteristics of certain internal emitters (such as radioiodine), and individual host factors.
The role of viruses in the etiology of cancer has been studied extensively. For example, researchers have inoculated laboratory animals with specific viruses to see whether tumor development is induced. Several human cancers show a definite correlation with viral infection and the presence and retention of specific virus nucleic acid sequences and virus proteins in the tumor cells. Table 13-1 lists several viruses and their associated cancers.
All the DNA virus groups have been associated with cancer, except the parvovirus family. This is notable because all the DNA viruses associated with cancer contain double-stranded DNA, whereas the parvoviruses contain only single-stranded DNA. Of the 9 RNA virus groups, only 1, the retrovirus group, is associated with oncogenicity. The papillomavirus of the papovavirus group has been associated with squamous cell carcinoma, cervical cancer, and laryngeal papilloma in humans. A vaccine against human papillomavirus (HPV) is now available. Immunization against HPV may prevent most cases of cervical cancer in women; see Chapter 12 for additional discussion.
Finally, cancers may aggregate in a nonrandom manner in certain families. These cancers may be of the same type or dissimilar. In such cancer-cluster families, several children may have soft tissue sarcoma and relatives may have a variety of cancers, especially breast cancer in young women. Multiple endocrine neoplasia types 1 and 2 are yet other examples of hereditary cancer syndromes. The recognition of familial cancer syndromes permits early detection that may be life-saving.
Table 13-1 Virus-Associated Cancers
Excerpted from BCSC 2020-2021 series: Section 1 - Update on General Medicine. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.