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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 the most common type of Down syndrome, who have 3 instead of the usual 2 copies of chromosome 21, have a 12 to 20 times higher risk of developing acute leukemia, but paradoxically, a lower risk of developing carcinomas.

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, medications, viruses, or other environmental agents. In some families, these abnormal cancer-causing genes are inherited.

The 2 major categories of genes involved with cancer are

• Oncogenes

• Tumor suppressor genes

Oncogenes are mutated or amplified forms of genes that in their normal state regulate cell growth. These oncogenes include HER2, which causes breast cancer and EGFR, which causes some lung cancers. Some oncogenes inappropriately signal cells to multiply in an uncontrolled manner, leading to a cancer. The mutation of normal genes to oncogenes is not entirely understood, but many factors may contribute, including

• Radiation

• Sunlight

• 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 or suppress the growth of cancerous cells. 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 adults. 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 cancers. Ionizing radiation is carcinogenic. X-ray studies (including computed tomography [CT]) use ionizing radiation, and people who have many tests have a small increased risk of cancer (see also 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 people who are exposed and 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 cancer and breast cancer is low in Japan, yet when people immigrate from Japan to the United States, the risk of colon and breast cancer increases and eventually equals that of the rest of the population of the United States. In contrast, people living in Japan have extremely high rates of stomach cancer. When people from Japan immigrate to the United States, their risk of stomach cancer declines to that of people in the United States, possibly due to a change in diet, 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, have 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 liver cancer, head and neck cancer, and esophageal cancer. A diet high in smoked and pickled foods or in barbecued meats increases the risk of developing stomach cancer. People who have overweight or obesity have a higher risk of cancer of the breast, lining of the uterus (endometrium), colon, kidneys, and esophagus.

Certain medications and medical treatments may increase the risk of developing cancer. For example, estrogens in oral contraceptives may slightly increase the risk of breast cancer in people who are currently taking them or who took them within the past few years. The hormones estrogen and progestin that may be given to women during menopause (hormone therapy) also slightly increase the risk of breast cancer.

Diethylstilbestrol (DES) increases the risk of breast cancer in women who took the medication and in daughters of these women who were exposed before birth. DES also increases the risk of cervical and vaginal cancer in daughters of women who took the medication. Tamoxifen, a medication used to treat breast cancer, increases the risk of endometrial cancer (cancer of the inner lining of the uterus).

Long-term use of testosterone, danazol, or other male hormones (androgens) may slightly increase the risk of liver cancer.

Treatment of cancer with certain chemotherapy medications (alkylating agents) and with radiation therapy may increase the risk of people developing a second cancer years later.

Several viruses are known to cause cancer in humans, and several others are suspected of causing cancer. The human papillomavirus (HPV), causes genital warts and is also is a major cause of cervical cancer and vulvar cancer in women, and penile cancer and anal cancer in men. HPV also causes some cancers of the mouth and throat. Hepatitis B virus or hepatitis C virus can cause liver cancer. Some human retroviruses, such as HIV, 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 Asia.

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. Infection with Schistosoma haematobium can cause chronic inflammation and scarring of the bladder, which may lead to cancer. Another type of parasite, Clonorchis sinensis, has been linked to pancreatic cancer and bile duct cancer.

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).