Brain Tumor Study in Adults  

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 to2002 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 2002also 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. A 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 adult 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 hospitals 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 acoutic 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 acoutic 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.