Many genetic and environmental factors increase the risk of developing cancer. However, not all people who are exposed to carcinogens or who have other risk factors develop cancer.
Family history and genetic factors
Some families have a significantly higher risk of developing certain cancers. Sometimes the increased risk is due to a single gene and sometimes it is due to several genes interacting together. Environmental factors—common to the family—may alter this genetic interaction and cause cancer.
An extra or abnormal chromosome may increase the risk of cancer. For example, people with Down syndrome, who have three instead of the usual two copies of chromosome 21, have a 12 to 20 times higher risk of developing acute leukemia, but paradoxically, a lower risk of developing carcinomas.
Genes That Cause Cancer
Abnormalities (mutations) affecting critical genes are believed to contribute to the development of cancer. These genes produce proteins that regulate growth and alter cell division and other basic cell properties.
Gene mutations causing cancer may result from the damaging effects of chemicals, sunlight, drugs, viruses, or other environmental agents. In some families, these abnormal cancer-causing genes are inherited.
The two major categories of genes involved with cancer are oncogenes and tumor suppressor genes.
Oncogenes are mutated or amplified forms of genes that in their normal state regulate cell growth. If they become overactive and signal cells to multiply in an uncontrolled manner, cancer may develop. The mutation of oncogenes is not entirely understood, but many factors may contribute, including
Toxins at work, in the air, or in chemicals (for example, in tobacco smoke)
Infectious agents (for example, certain viruses)
Tumor suppressor genes normally suppress the development of cancers by coding for proteins that repair damaged DNA and suppress growth. Cancer is more likely when DNA damage impairs tumor suppressor gene function, allowing affected cells to multiply continuously. Suppressor gene mutations, inherited from a parent, may underlie a certain percentage of cases of breast cancer, usually occurring at a young age and in multiple family members.
Some cancers, such as Wilms tumor, retinoblastoma, and neuroblastoma, occur almost exclusively in children. These cancers result from suppressor gene mutations that are either inherited or that occur during fetal development. However, most other cancers are more common in adults, particularly in older people. In the United States, more than 60% of cancers occur in people older than 65. The increased cancer rate is probably due to a combination of increased and prolonged exposure to carcinogens and weakening of the body’s immune system.
Numerous environmental factors increase the risk of developing cancer.
Tobacco smoke contains carcinogens that substantially increase the risk of developing cancers of the lungs, mouth, throat, esophagus, kidneys, and bladder.
Pollutants in the air or water, such as asbestos, industrial waste, or cigarette smoke, can increase the cancer risk. Many chemicals are known to cause cancer, and many others are suspected of doing so. For example, asbestos exposure may cause lung cancer and mesothelioma (cancer of the pleura). Exposure to pesticides is associated with a higher risk of some types of cancer (for example, leukemia and non-Hodgkin lymphoma). The time between exposure to the chemicals and development of the cancer may be many years.
Exposure to radiation is a risk factor for the development of cancer. Extended exposure to ultraviolet radiation, primarily from sunlight, causes skin cancer. Ionizing radiation is particularly carcinogenic. X-rays (including computed tomography [CT]) use ionizing radiation, and people who have many tests that use high doses of x-rays have an increased risk of cancer (see Overview of Imaging Tests : Risks of Radiation in Medical Imaging). Exposure to the radioactive gas radon, which is released from soil, increases the risk of lung cancer. Normally, radon disperses rapidly into the atmosphere and causes no harm. However, when a building is placed on soil with a high radon content, radon can accumulate within the building, sometimes causing levels in the air that are sufficiently high enough to cause harm. Radon is breathed into the lungs, where it may eventually cause lung cancer. In exposed people who also smoke, the risk of lung cancer is further increased.
Many other substances have been investigated as possible causes of cancer, but more study is needed to identify those chemicals that increase the risk of cancer.
The risk of cancer varies according to where people live, although the reasons for the geographic differences are often complex and poorly understood. This geographic variation in cancer risk is probably multifactorial: a combination of genetics, diet, and environment.
For example, the risk of colon and breast cancers is low in Japan, yet in Japanese people who immigrate to the United States, the risk increases and eventually equals that of the rest of the American population. In contrast, the Japanese have extremely high rates of stomach cancer. When these people immigrate to the United States and eat a Western diet, the risk declines to that of the United States, although the decline may not be evident until the next generation.
Substances consumed in the diet can increase the risk of cancer. For instance, a diet high in unsaturated fat, and obesity by itself, has been linked to an increased risk of colon, breast, and possibly prostate cancer. People who drink large amounts of alcohol are at much higher risk of developing head and neck and esophageal cancer. A diet high in smoked and pickled foods or in barbecued meats increases the risk of developing stomach cancer. People who are overweight or obese have a higher risk of cancer of the breast, lining of the uterus (endometrium), colon, kidneys, and esophagus.
Drugs and medical treatments
Certain drugs and medical treatments may increase the risk of developing cancer. For example, estrogens in oral contraceptives may slightly increase the risk of breast cancer, but this risk decreases over time. The hormones estrogen and progestin that may be given to women during menopause (hormone replacement therapy) also increase the risk of breast cancer. Diethylstilbestrol (DES) increases the risk of breast cancer in women who took the drug and in daughters of these women who were exposed before birth. Tamoxifen, a drug used to treat breast cancer, increases the risk of endometrial cancer. Long-term use of testosterone or other male hormones (androgens) may slightly increase the risk of liver cancer. Treatment of cancer with certain chemotherapy drugs (alkylating agents) and with radiation therapy may increase the risk of people developing a second cancer years later.
Type of Cancer
Environmental and industrial
Associated with lifestyle
Used in medicine
Chemotherapy drugs (such as alkylating drugs and topoisomerase inhibitors)
Breast (in women who took the drug and in women exposed before birth)
Cervix (when exposed before birth)
Endometrium (in women who took the drug)
Vagina (when exposed before birth)
Several viruses are known to cause cancer in humans, and several others are suspected of causing cancer. The human papillomavirus (HPV, which causes genital warts) is a major cause of cervical cancer in women and penile and anal cancer in men. HPV also causes some cancers of the throat. Hepatitis B virus or hepatitis C virus can cause liver cancer. Some human retroviruses cause lymphomas and other cancers of the blood system. Some viruses cause types of cancer in certain countries but not in others. For instance, the Epstein-Barr virus causes Burkitt lymphoma (a type of cancer) in Africa and cancers of the nose and pharynx in China.
Some bacteria also may cause cancer. Helicobacter pylori, which causes stomach ulcers, can increase the risk of stomach cancer and lymphomas.
Some parasites can cause cancer. Schistosoma haematobium can cause chronic inflammation and scarring of the bladder, which may lead to cancer. Another type of parasite, Opisthorchis sinensis, has been linked to cancer of the pancreas and bile ducts.
Inflammatory disorders often increase the risk of cancer. Such disorders include ulcerative colitis and Crohn disease (which can result in colon cancer and bile duct cancers).
When cells become cancerous, new antigens—unfamiliar to the immune system—appear on the cell’s surface. These antigens are called tumor antigens. Which of the following may be the immune system’s response to tumor antigens?