In 1994, researchers at the National Cancer Institute (NCI) initiated a comprehensive study on the causes of brain tumors in adults. Because the causes of brain tumors are largely unknown, the scientists are evaluating a wide range of environmental, lifestyle, and genetic factors that may influence the risk for developing brain tumors. These include:

• Cellular phone use;
• Occupational exposures, such as solvents, pesticides, lead, and electromagnetic fields (EMFs) from electrical machinery;
• Family history of cancer;
• Dietary factors, including processed meats, artificial sweeteners, and vitamin and mineral supplements;
• Medical history such as allergies, head trauma and radiation exposures;
• Reproductive history and hormone use;
• Use of hair dyes; and
• Possible susceptibility genes.

As the results from the brain tumor study are published in various scientific journals over the next few years, the findings will be referenced and summarized at the end of this fact sheet.

Background

Statistics

Each year about 19,000 people in the United States are diagnosed with primary brain cancers. Brain and other nervous system cancers, however, make up a small percentage of the new cases of cancer in the United States—between 1 percent to 2 percent. The five-year survival for brain and other nervous system cancers from 1997 to 2002 was about 33 percent; this means that 33 percent of brain cancer patients survive at least five years after their tumor is diagnosed. (Survival, incidence, and death rates do not include people with benign tumors.)

The risk of developing brain cancer increases with age. The rate for people under age 65 is 4.5 for every 100,000 people in the United States compared to 17.8 for persons 65 and older.

Trends Over Time

From 1990 to 2002, the overall age-adjusted incidence rates for brain cancer decreased slightly; from 7.0 cases to 6.4 cases for every 100,000 persons in the United States. The mortality rate from 1990 to 2002 also decreased slightly; from 4.9 deaths to 4.4 for every 100,000 persons in the United States. The incidence and mortality rates for cancers that originate in the brain and central nervous system have remained relatively unchanged in the last decade.

Looking at long term trends for specific age groups, there is an increase in incidence and this is due, at least in part, to the improvements in the ability to diagnose brain tumors in elderly patients. The increased use of CT (computed tomography), MRI (magnetic resonance imaging) and stereotactic biopsy procedures (more precise methods for locating and diagnosing tumors) correlates with the increased incidence trends, and represents a greater tendency of physicians to aggressively pursue brain diagnoses in older patients.

Types of Brain Tumors

Primary brain tumors are tumors that arise in the brain, unlike tumors that begin elsewhere in the body and then spread to the brain. They are classified by the type of cell in which they develop. The most common brain tumors are gliomas. Gliomas develop in the glial cells which make up the soft, spongy tissue that supports the nerve cells in the brain. There are several types of gliomas. One type, astrocytoma, arises from small, star-shaped cells called astrocytes, and can grow anywhere in the brain or spinal cord. In adults, astrocytomas most often arise in the cerebrum, the largest part of the brain that fills most of the upper skull. Glioblastoma is an especially malignant form of astrocytoma. Oligodendroglioma and ependymoma are other types of gliomas. Gliomas are more common among men than women.

When people say "brain cancer," they usually are referring to glioma or medulloblastoma. Medulloblastoma is a type of brain cancer that occurs primarily in children. Brain tumor is a more general term and includes benign as well as malignant tumors.

Meningiomas are brain tumors which develop in the meninges, the protective membrane covering the brain directly underneath the skull. These tumors are usually benign and grow slowly. They occur more often in women than men.

Schwannomas are benign tumors that develop in Schwann cells. Schwann cells produce the myelin that covers and protects the peripheral or cranial nerve fibers connected with the brain.

Acoustic neuromas are a type of schwannoma that occurs in the nerve between the brain and the ear. They occur primarily in adults.

Among adults, the most frequent types of brain tumors are glioblastoma and other astrocytic tumors, meningiomas, acoustic neuromas, and pituitary gland tumors. Less common types include oligodendroglioma, ependymoma, lymphomas, vascular tumors, and tumors of the pineal gland.

Risk Factors

There are only a few well-established risk factors for brain tumors. People receiving radiotherapy (high-dose ionizing radiation) to the head during childhood are at increased risk for developing brain tumors, as are people with certain rare genetic disorders such as neurofibromatosis and Li-Fraumeni syndrome.

The risk associated with low doses of ionizing radiation is less clear; radiation from modern diagnostic X-rays probably carries minimal risk. (Ionizing radiation, either gamma or X-rays, is high frequency radiation and can cause the breaking of molecular bonds, damaging genetic material, DNA).

The molecular and health effects in humans of low frequency, non-ionizing radiation such as that produced by electrical appliances, power lines, or cell phones show no consistent association. The available data on electromagnetic fields (EMF) produced by electrical appliances or electric power lines are insufficient to support the conclusion that low-frequency fields cause cancer. Similarly, early reports on the use of cell phones for five years or less do not show an association with brain tumor risk.

There have been several epidemiologic studies suggesting that nervous system cancers may be related to a variety of environmental exposures, including N-nitroso compounds (e.g., nitrosamides or nitrosamines) and some solvents. In addition, an excess risk has been suggested among workers in certain industries such as farming, the manufacture of synthetic rubber and polyvinyl chloride, the refining of crude oil, the production of petroleum-based chemicals, and the manufacture of pharmaceuticals. Certain professional groups, as well, such as electrical workers, chemists, embalmers, pathologists, and artists have been reported to have higher than expected brain cancer rates.

However, aside from the small percentage of brain tumor cases that can be linked to exposure to high-dose ionizing radiation or to certain inherited genetic alterations, few specific risk factors have been convincingly linked to brain tumors.

Patient Population

The NCI study of brain tumors in adults includes 782 brain tumor cases and 799 controls from three medical institutions: St. Joseph's Hospital and Medical Center in Phoenix; Brigham and Women's Hospital in Boston; and Western Pennsylvania Hospital in Pittsburgh. The controls are people who were admitted to the same hospitals as the brain tumor cases for treatment of a variety of non-cancerous conditions. Controls were matched with cases by hospital, sex, race, age and distance of residence from hospital. Data collection began in 1994 and was completed in 1998.

The study included brain tumor patients recently diagnosed with glioma (489 cases), meningioma (197 cases) or acoustic neuroma (96 cases). Patients with tumors that originated in other parts of the body and then spread to the brain were not included. The study was restricted to adults who were age 18 or older who received care at one of the participating hospitals, and could understand English or Spanish. The participants from the Boston and Pittsburgh hospitals lived within 50 miles of the hospital while those from the Phoenix hospital were from the State of Arizona.

Data Collection

Data were collected through computer-assisted patient interviews. A structured personal interview was done by a research nurse to obtain information about the use of portable telephones, occupational history, including workplace exposures to chemicals and electromagnetic fields, hobbies with potential for solvent exposures, personal and family medical history, reproductive history and hormonal exposures, and use of tobacco and hair coloring products. Education, marital status, place of birth, and household income information was also collected. If the patient had died or was too ill to conduct the interviews, the spouse or another close family member answered the questions.

In addition to the personal interview, a self-administered paper questionnaire covering diet, alcohol consumption, vitamin supplements, and home use of electrical appliances was completed by each participant or a close family member.

Blood samples were collected to explore a variety of questions related to inherited gene mutations or polymorphisms that might influence sensitivity to cancer-causing agents, and to assay for biological markers that may reveal past environmental exposures.

Results/Publications

• There was no evidence of higher brain tumor risk among people who use hand-held cellular phones compared to those who do not use them.

The risk of developing brain tumors did not increase with increasing years of use or average minutes of use per day, nor did brain tumors among cellular phone users tend to occur more often than expected on the side of the head on which people reported using their phone. There was no evidence that the risk of any of the three major categories of tumors included in the study (glioma, meningioma, or acoustic neuroma) was increased among persons who used cellular telephones 60 or more minutes per day, or regularly for up to five years. However, if an increased risk occurs only after five or more years, or only among very heavy users, this study would not have detected it. Also, the study was done when most cellular phones were analogue phones, whereas today most people use digital phones.

Reference: Inskip PD, Tarone RE, Hatch EE, Wilcosky TC, Shapiro WR, Selker RG, Fine HA, Black PM, Loeffler JS, Linet MS. Cellular telephone use and brain tumors. N Engl J Med 2001;344:79–86.

• There was evidence that people with a history of allergies or autoimmune diseases were at reduced risk of developing glioma. In addition, people with a history of both allergies and autoimmune diseases appeared to be at the lowest risk of developing glioma.

Allergies evaluated included asthma, eczema, hay fever, and allergies to medicine, insects, food, and chemicals. Autoimmune diseases included rheumatoid arthritis, lupus erythematosus, multiple sclerosis, diabetes, and pernicious anemia. Asthma and diabetes showed the most consistent associations.

The reduced risk associated with history of allergies was specific for gliomas, as there was no significant association between history of allergies and risk of meningioma or acoustic neuroma. History of autoimmune disease, however, was associated with a reduced risk of both glioma and meningioma. The reasons for these associations are unclear and require further investigation.

Reference: Brenner AV, Linet MS, Fine HA, Shapiro WR, Selker RG, Black PM, Inskip PD. History of allergies and autoimmune diseases and risk of brain tumors in adults. Int J Cancer 2002;99:252–259.

• Researchers found that polymorphisms in certain gene families are associated with an increased incidence of brain tumors, while others are not.

Investigators examined the association between the incidence of brain tumors and polymorphisms in GST (glutathione S-transferase) and CYP (cytochrome P450), two families of genes involved in the metabolism of solvents that may play a role in the development of brain tumors. GSTP1 105 Val/Val was associated with an 80 percent increased incidence of glioma. CYP2E1 RsaI was weakly associated with an increased incidence of glioma and acoustic neuroma, with some indication of a stronger association among younger subjects. Neither GSTM1 nor GSTP1 I114V was associated with the risk of developing any of the tumor types.

Reference: De Roos AJ, Rothman N, Inskip PD, Linet MS, Shapiro WR, Selker RG, Fine HA, Black PM, Pittman GS, Bell DA. Genetic Polymorphisms in GSTM1, -P1, -T1 and CYP2E1 and the Risk of Adult Brain Tumors. Cancer Epidemiol Biomarkers Prev 2003;12:14–27.

• The risk of developing glioma, meningioma, or acoustic neuroma was not associated with having received either injected or oral polio vaccine during the time period when vaccines were contaminated with SV40.

Through the mass immunization program for polio, it is estimated that 10 million to 30 million people in the United States from 1955–1963 were inadvertently exposed to live SV40 virus through contaminated vaccines. In some studies, SV40 DNA has been detected in rare brain tumors (i.e., ependymoma and choroid plexus tumors), suggesting a possible link between exposure to SV40 and certain types of brain cancer.

In this study, however, the risk of developing glioma, meningioma, or acoustic neuroma was not associated with having received either injected or oral polio vaccine during the time period when vaccines were contaminated with SV40. Exposure to the vaccine was based on self-reporting. Although some participants may not have been able to recall vaccinations they received as young children, the high percentage (85 percent) of reported vaccination among controls, who were less than 20 years of age in 1961 and would have been likely to receive the vaccine, was similar to the values reported for the same period in another study.

Reference: Brenner AV, Linet MS, Selker RG, Shapiro WR, Black PM, Fine HA, Inskip PD. Polio Vaccination and risk of brain tumors in adults: no apparent association. Cancer Epidemiol Biomarkers Prev 2003;12:177–178.

Related Links:

"No Association Found Between Cellular Phone Use and Risk of Brain Tumors."
http://www.cancer.gov/newscenter/cellphassoc

"National Cancer Institute Study of Brain Tumors and Use of Cellular Telephones."
http://www.cancer.gov/cancertopics/factsheet/brain-tumors-cell-phones

Basic information about brain tumors:
http://www.cancer.gov/cancertopics/wyntk/brain

# # #

*Inskip PD, Hatch EE, Stewart PA, Heineman EF, Ziegler RG, Dosemeci M, et al. Study design for a case-control investigation of cellular telephones and other risk factors for brain tumors in adults. Radiat Prot Dosim 1999;86:42–45.

# # #

Related NCI materials and Web pages:

• National Cancer Institute Fact Sheet 3.46, Magnetic Field Exposure and Cancer: Questions and Answers ¹
  (http://www.cancer.gov/cancertopics/factsheet/Risk/magnetic-fields)
• National Cancer Institute Fact Sheet 3.72, Cellular Telephone Use and Cancer Risk ²
  (http://www.cancer.gov/cancertopics/factsheet/Risk/cellphones)
• Cancer Causes and Risk Factors Home Page ³
  (http://www.cancer.gov/cancertopics/prevention-genetics-causes/causes)
• What You Need To Know About™ Brain Tumors ⁴
  (http://www.cancer.gov/cancertopics/wyntk/brain)
• Brain Tumor Home Page ⁵
  (http://www.cancer.gov/cancertopics/types/brain)

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Glossary Terms

Having to do with sound or hearing.

A disease that causes inflammation and pain in the joints.

A laboratory test to find and measure the amount of a specific substance.

A chronic disease in which the bronchial airways in the lungs become narrowed and swollen, making it difficult to breathe. Symptoms include wheezing, coughing, tightness in the chest, shortness of breath, and rapid breathing. An attack may be brought on by pet hair, dust, smoke, pollen, mold, exercise, cold air, or stress.

A large, star-shaped cell that holds nerve cells in place and helps them develop and work the way they should. An astrocyte is a type of glial cell.

A tumor that begins in the brain or spinal cord in small, star-shaped cells called astrocytes.

A condition in which the body recognizes its own tissues as foreign and directs an immune response against them.

Not cancerous. Benign tumors may grow larger but do not spread to other parts of the body. Also called nonmalignant.

A growth that is not cancer. It does not invade nearby tissue or spread to other parts of the body.

Pertaining to biology or to life and living things. In medicine, refers to a substance made from a living organism or its products. Biologicals may be used to prevent, diagnose, treat or relieve of symptoms of a disease. For example, antibodies, interleukins, and vaccines are biologicals. Biological also refers to parents and children who are related by blood.

A tissue with red blood cells, white blood cells, platelets, and other substances suspended in fluid called plasma. Blood takes oxygen and nutrients to the tissues, and carries away wastes.

The growth of abnormal cells in the tissues of the brain. Brain tumors can be benign (not cancer) or malignant (cancer).

A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is a cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is a cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is a cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord. Also called malignancy.

The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.

The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. Areas within the cerebrum control muscle functions and also control speech, thought, emotions, reading, writing, and learning.

A series of detailed pictures of areas inside the body taken from different angles. The pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computerized axial tomography scan, computerized tomography, and CT scan.

A series of detailed pictures of areas inside the body taken from different angles. The pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography scan, computerized axial tomography scan, and computerized tomography.

Any of several diseases in which the kidneys make a large amount of urine. Diabetes usually refers to diabetes mellitus in which there is also a high level of glucose (a type of sugar) in the blood because the body does not make enough insulin or use it the way it should.

The process of identifying a disease, such as cancer, from its signs and symptoms.

The things a person eats and drinks.

In medicine, a disturbance of normal functioning of the mind or body. Disorders may be caused by genetic factors, disease, or trauma.

The molecules inside cells that carry genetic information and pass it from one generation to the next. Also called deoxyribonucleic acid.

The amount of medicine taken, or radiation given, at one time.

A type of brain tumor that begins in cells lining the spinal cord central canal (fluid-filled space down the center) or the ventricles (fluid-filled spaces of the brain). Ependymomas may also form in the choroid plexus (tissue in the ventricles that makes cerebrospinal fluid). Also called ependymal tumor.

A record of the relationships among family members along with their medical histories. This includes current and past illnesses. A family history may show a pattern of certain diseases in a family. Also called family medical history.

The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein.

Inherited; having to do with information that is passed from parents to offspring through genes in sperm and egg cells.

A fast-growing type of central nervous system tumor that forms from glial (supportive) tissue of the brain and spinal cord and has cells that look very different from normal cells. Glioblastoma usually occurs in adults and affects the brain more often than the spinal cord. Also called GBM, glioblastoma multiforme, and grade IV astrocytoma.

A cancer of the brain that begins in glial cells (cells that surround and support nerve cells).

A family of enzymes involved in metabolism and in making toxic compounds less harmful to the body.

One of many chemicals made by glands in the body. Hormones circulate in the bloodstream and control the actions of certain cells or organs. Some hormones can also be made in the laboratory.

A technique used to cause an immune response that results in resistance to a specific disease, especially an infectious disease.

The number of new cases of a disease diagnosed each year.

Transmitted through genes that have been passed from parents to their offspring (children).

Use of a syringe and needle to push fluids or drugs into the body; often called a "shot."

A type of radiation made (or given off ) by x-ray procedures, radioactive substances, rays that enter the Earth's atmosphere from outer space, and other sources. At high doses, ionizing radiation increases chemical activity inside cells and can lead to health risks, including cancer.

A rare, inherited predisposition to multiple cancers, caused by an alteration in the p53 tumor suppressor gene.

A chronic, inflammatory, connective tissue disease that can affect the joints and many organs, including the skin, heart, lungs, kidneys, and nervous system. It can cause many different symptoms; however, not everyone with lupus has all of the symptoms. Also called SLE and systemic lupus erythematosus.

Cancer that begins in cells of the immune system. There are two basic categories of lymphomas. One kind is Hodgkin lymphoma, which is marked by the presence of a type of cell called the Reed-Sternberg cell. The other category is non-Hodgkin lymphomas, which includes a large, diverse group of cancers of immune system cells. Non-Hodgkin lymphomas can be further divided into cancers that have an indolent (slow-growing) course and those that have an aggressive (fast-growing) course. These subtypes behave and respond to treatment differently. Both Hodgkin and non-Hodgkin lymphomas can occur in children and adults, and prognosis and treatment depend on the stage and the type of cancer.

A procedure in which radio waves and a powerful magnet linked to a computer is used to create detailed pictures of areas inside the body. These pictures can show the difference between normal and diseased tissue. Magnetic resonance imaging makes better images of organs and soft tissue than other scanning techniques, such as computed tomography (CT) or x-ray. Magnetic resonance imaging is especially useful for imaging the brain, the spine, the soft tissue of joints, and the inside of bones. Also called MRI, NMRI, and nuclear magnetic resonance imaging.

Cancerous. Malignant tumors can invade and destroy nearby tissue and spread to other parts of the body.

A diagnostic indication that disease may develop.

A malignant brain tumor that begins in the lower part of the brain and that can spread to the spine or to other parts of the body. Medulloblastomas are a type of primitive neuroectodermal tumor (PNET).

A very thin layer of tissue that covers a surface.

The three thin layers of tissue that cover and protect the brain and spinal cord.

A type of slow-growing tumor that forms in the meninges (thin layers of tissue that cover and protect the brain and spinal cord). Meningiomas usually occur in adults.

The total of all chemical changes that take place in a cell or an organism. These changes make energy and the materials needed for growth, reproduction, and maintaining health. They also help get rid of toxic substances.

In medicine, a mineral is a nutrient that is needed in small amounts to keep the body healthy. Mineral nutrients include the elements calcium, magnesium, and iron.

A procedure in which radio waves and a powerful magnet linked to a computer is used to create detailed pictures of areas inside the body. These pictures can show the difference between normal and diseased tissue. MRI makes better images of organs and soft tissue than other scanning techniques, such as computed tomography (CT) or x-ray. MRI is especially useful for imaging the brain, the spine, the soft tissue of joints, and the inside of bones. Also called magnetic resonance imaging, NMRI, and nuclear magnetic resonance imaging.

A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid), serving as a nerve insulator and helping in the transmission of nerve signals.

Any change in the DNA of a cell. Mutations may be caused by mistakes during cell division, or they may be caused by exposure to DNA-damaging agents in the environment. Mutations can be harmful, beneficial, or have no effect. If they occur in cells that make eggs or sperm, they can be inherited; if mutations occur in other types of cells, they are not inherited. Certain mutations may lead to cancer or other diseases.

The fatty substance that covers and protects nerves.

A bundle of fibers that receives and sends messages between the body and the brain. The messages are sent by chemical and electrical changes in the cells that make up the nerves.

A tumor that arises in nerve cells.

A health professional trained to care for people who are ill or disabled.

A rare, slow-growing tumor that begins in oligodendrocytes (cells that cover and protect nerve cells in the brain and spinal cord). Also called oligodendroglial tumor.

By or having to do with the mouth.

A type of anemia (low red blood cell count) caused by the body's inability to absorb vitamin B12.

Medical doctor.

A tiny organ in the cerebrum that produces melatonin. Also called pineal body and pineal organ.

The main endocrine gland. It produces hormones that control other glands and many body functions, especially growth.

A common change in the genetic code in DNA. Polymorphisms can have a harmful effect, a good effect, or no effect. Some polymorphisms have been shown to increase the risk of certain types of cancer.

Energy released in the form of particle or electromagnetic waves. Common sources of radiation include radon gas, cosmic rays from outer space, medical x-rays, and energy given off by a radioisotope (unstable form of a chemical element that releases radiation as it breaks down and becomes more stable).

The use of high-energy radiation from x-rays, gamma rays, neutrons, protons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body near cancer cells (internal radiation therapy). Systemic radiotherapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that travels in the blood to tissues throughout the body. Also called irradiation and radiation therapy.

Something that increases the chance of developing a disease. Some examples of risk factors for cancer are age, a family history of certain cancers, use of tobacco products, being exposed to radiation or certain chemicals, infection with certain viruses or bacteria, and certain genetic changes.

A tumor of the peripheral nervous system that arises in the nerve sheath (protective covering). It is almost always benign, but rare malignant schwannomas have been reported.

In statistics, describes a mathematical measure of difference between groups. The difference is said to be significant if it is greater than what might be expected to happen by chance alone. Also called statistically significant.

A column of nerve tissue that runs from the base of the skull down the back. It is surrounded by three protective membranes, and is enclosed within the vertebrae (back bones). The spinal cord and the brain make up the central nervous system, and spinal cord nerves carry most messages between the brain and the rest of the body.

A biopsy procedure that uses a computer and a 3-dimensional scanning device to find a tumor site and guide the removal of tissue for examination under a microscope.

Adding nutrients to the diet.

A group or layer of cells that work together to perform a specific function.

A plant with leaves that have high levels of the addictive chemical nicotine. The leaves may be smoked (in cigarettes, cigars, and pipes), applied to the gums (as dipping and chewing tobacco), or inhaled (as snuff). Tobacco leaves also contain many cancer-causing chemicals, and tobacco use and exposure to secondhand tobacco smoke have been linked to many types of cancer and other diseases. The scientific name is Nicotiana tabacum.

Treatment with a vaccine.

A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. A vaccine can help the body recognize and destroy cancer cells or microorganisms.

In medicine, a very simple microorganism that infects cells and may cause disease. Because viruses can multiply only inside infected cells, they are not considered to be alive.

A nutrient that the body needs in small amounts to function and stay healthy. Sources of vitamins are plant and animal food products and dietary supplements. Some vitamins are made in the human body from food products. Vitamins are either fat-soluble (can dissolve in fats and oils) or water-soluble (can dissolve in water). Excess fat-soluble vitamins are stored in the body’s fatty tissue, but excess water-soluble vitamins are removed in the urine. Examples are vitamin A, vitamin C, and vitamin E.

A type of high-energy radiation. In low doses, x-rays are used to diagnose diseases by making pictures of the inside of the body. In high doses, x-rays are used to treat cancer.