Potential Link Between Genetics and Development of Brain Tumors

Newswise — Individuals with a particular genotype have a heightened susceptibility to a type of brain tumor known as meningioma, according to a study published today in the September issue of the peer-reviewed journal Environmental Health Perspectives (EHP). The study, part of a growing effort to explore the development of brain tumors, is an analysis of data from one of the largest case"control studies of brain tumors to date.

Previous research indicates that occupational exposure to lead may increase the risk of meningioma. Other studies suggest that people who carry the ALAD2 polymorphism of the gene that codes for d-aminolevulinic acid dehydratase have higher concentrations of lead in their blood.

With very little known about the etiology of brain tumors, this analysis theorized that the ALAD2 genetic variant may be associated with increased risk of developing meningioma, a tumor that occurs in the membranes covering the brain and the spinal cord.

Subjects in the National Cancer Institute's Brain Tumor Study were patients at three hospitals specializing in brain tumor treatment, located in Phoenix, Boston, and Pittsburgh. They were enrolled from 1994 to 1998.

Eligible cases for the study were aged 18 years or older, with a first intracranial glioma, meningioma, or acoustic neuroma diagnosed during or within the eight weeks preceding hospitalization. A total of 573 cases were evaluated for the presence of the ALAD2 variant.

A total of 505 controls— patients admitted to the same hospitals for a variety of conditions not involving tumors—were also evaluated. Controls were matched to brain tumor cases based on hospital, age, sex, race/ethnicity, and proximity of residence to the hospital.

This analysis of data collected in the Brain Tumor Study found that people who carried the ALAD2 gene variant were 1.6 times more likely to develop meningioma than were individuals with the more common form of the gene. This association was stronger in males, who were 3.5 times more likely to develop meningioma if they carried the ALAD2 variant.

The study authors caution that the sample size for sex-specific estimates may be too small to draw solid conclusions, and that higher rates for males could be due to biological differences, different levels of exposure to a chemical agent modified by ALAD genotype, or chance.

Since other studies have shown that individuals who carry the ALAD2 variant are more likely to have higher levels of lead in their blood, the current results suggest that lead exposure may play a role in the link between the ALAD2 form and meningioma.

"In a previously published analysis of this same data set, we found elevated risk of meningioma in individuals who had worked in military occupations or as autobody painters, designers and decorators, industrial production supervisors, teachers, or managers. Aside from teachers and managers, all of these occupations have potential exposure to lead," the study authors wrote.

The authors of the analysis caution, however, against overinterpretation of the findings. They underline the need for replication of the results, and state that future studies are needed to consider the combined effects of exposure to lead and the ALAD variant on the frequency of meningioma.

The lead author of the study was Preetha Rajaraman of the Divison of Cancer Epidemiology and Genetics, National Cancer Institute. Other authors included Brian S. Schwartz, Nathaniel Rothman, Meredith Yeager, Howard A. Fine, William R. Shapiro, Robert G. Selker, Peter M. Black, and Peter D. Inskip. The article is available free of charge at http://ehp.niehs.nih.gov/members/2005/7986/7986.html.

EHP is published by the National Institute of Environmental Health Sciences, part of the U.S. Department of Health and Human Services. EHP is an Open Access journal. More information is available online at http://www.ehponline.org/. Brogan & Partners Convergence Marketing handles marketing and public relations for EHP, and is responsible for creation and distribution of this press release.