Cancer Health Article

Causes of Cancer

The exact cause of cancer is not known. Most cancers result from permanent damage to genes or from mutations, which occur either due to internal factors, such as hormones, immune conditions, metabolism, and the digestion of nutrients within cells, or by exposure to environmental or external factors. A chemical or other environmental agent that produces cancer is called a carcinogen.

Overall, environmental factors, defined broadly to include tobacco use, diet, infectious diseases, chemicals, and radiation, are believed to cause between 75 and 80 percent of all cancer cases in the United States. Tobacco use, including cigarettes, cigars, chewing tobacco, and snuff, can cause cancers of the lung, mouth, throat, larynx, bladder, kidney, esophagus, and pancreas. Smoking alone causes one-third of all cancer deaths in the United States. Heavy consumption of alcohol has also been shown to increase the risk of developing cancer of the mouth, pharynx, larynx, esophagus, liver, and breast.

Overweight and obesity are associated with increased risk of cancers of the breast, colon, endometrium, esophagus, kidney, and gallbladder. The following chemicals have been found to cause cancer: coal tars and their derivatives, such as benzene; some hydrocarbons; aniline, a substance used to make dyes; and asbestos. Radiation from a variety of sources, including the ultraviolet light from the sun, is known to lead to skin cancer.

Several infectious agents have also been implicated in cancer. Evidence suggests that chronic viral infections are associated with up to one-fifth of all cancers. These include hepatitis B virus (HBV), which can lead to cancer of the liver; the Epstein-Barr virus, a type of herpes virus that causes infectious mononucleosis and has been associated with Hodgkin's disease, non-Hodgkin's lymphomas, and nasopharyngeal cancer; the human immunodeficiency virus (HIV), which is associated with an increased risk of developing several cancers, especially Kaposi's sarcoma and non-Hodgkin's lymphoma; and human papilloma viruses (HPV), which have been proven to cause cervical cancer and have also been associated with cancers of the vagina, vulva, penis, and colon. The bacterium Helicobacter pylori has been linked to stomach cancer.

About 5 to 10 percent of cancers are hereditary, in that a faulty gene or damaged DNA that has been inherited predisposes a person to be at a very high risk of developing a particular cancer. Two genes, BRCA1 and BRCA2, have been found to cause some breast cancers. Other genes have been discovered that are associated with some cancers that run in families, such as cancers of the colon, rectum, kidney, ovary, esophagus, lymph nodes, skin melanoma, and pancreas.

Carcinogenesis Process

All cancers involve the malfunction of genes that control cell growth and division. The process by which cancers develop is called carcinogenesis. This process usually starts when chemicals or radiation damage DNA, the genetic structure inside cells. Viruses induce carcinogenesis by introducing new DNA sequences. Most of the time, when DNA becomes damaged the body is able to repair it. In cancer cells, however, the damaged DNA is not repaired. While normal cells with damaged DNA die, cancer cells with damaged DNA continue to multiply.

There is a long time lag between exposure to a carcinogen and the occurrence of cancer. While cellular mutations cause cancer to develop, it is not exactly clear how this happens. Carcinogenesis is a multistep process, in which as many as ten distinct mutations may have to accumulate in a cell before it becomes cancerous. The fact that so many mutations are needed for a cancer to develop indicates that cell growth is normally controlled through many sets of checks and balances.

The cell cycle is regulated by a large number of cellular genes that are expressed, or exhibited, at different stages of the cycle. The genes code for, or determine, growth factors, growth-factor receptors, and proteins that control gene functions and cell survival. Damaged DNA can lead to cancer because the cell cycle is distorted by the alteration and activation of oncogenes, genes that stimulate cell growth, or by the inactivation of tumor suppressor genes, which ordinarily suppress cell growth. Activated oncogenes drive abnormal, unregulated cell proliferation and lead to tumor formation. Mutations of the tumor suppressor gene p53 are found in about 50 percent of human cancers.

In experimental animals, three stages of chemical carcinogenesis have been identified. These are: (1) initiation, where DNA is irreversibly altered; (2) promotion, which is the multiplication of altered cells; and (3) progression, which involves chromosomal changes, high growth rate, invasiveness, and potential to metastasize.