Immune Response Protects Against Brain Tumor Development
In their quest to determine whether immune system surveillance guards against brain tumor development, researchers at The University of Texas M. D. Anderson Cancer Center have found that allergies and asthma that stimulate inflammation may be protective, but use of antihistamines to control the inflammation could eliminate that protection.
In this study, reported at the annual meeting of the American Association for Cancer Research (AACR), the researchers also associated chicken pox infection with a significantly reduced risk of developing brain tumors.
The researchers say the findings suggest that a small amount of inflammation in the brain may rev up the immune system enough to protect against brain tumor development. But they stress that no one should give up antihistamines or shun use of a chicken pox vaccine because of this study.
"Brain tumors are exceedingly rare, and many, many people use antihistamines, so we certainly are not suggesting a direct connection between the two, or between chicken pox and tumors," says the study's lead author, Melissa Bondy, Ph.D., a professor in the Department of Epidemiology. "What this study may do is help us begin to understand if the immune system plays a role in development of different kinds of brain tumors."
"Our long-term goal is to look at genes that may be increasing or reducing risk of developing these tumors, and then to assess whether some individuals might be genetically susceptible," says Michael E. Scheurer, Ph.D., a postdoctoral fellow in the Department of Epidemiology.
In this study, Scheurer and Bondy combined data from their large Harris County, Texas, epidemiological study of brain tumor patients with information collected on patients in the San Francisco area by researchers at the University of California, San Francisco. Together, they compared medical histories of 830 brain tumor patients matched to a control group of 831 individuals. Within the patient group were 339 cases of glioblastoma (GBM), the most aggressive and lethal type of brain tumor, as well as 117 cases of midgrade anaplastic astrocytoma (AA) and 154 cases of low-grade gliomas (LGG).
The research team considered recent studies that suggest immune system activity in the brain may protect against brain tumor development and that people who have allergies or asthma have a reduced risk of developing a glioma.
"It could be that allergies and asthma produce enough inflammation in the brain to keep immune system cells active, and that this surveillance works to eliminate cancer beginning to develop in the brain," Scheurer says. "So we wondered whether use of antihistamines that counter that inflammation eliminates the protective effect."
They found that, indeed, a history of allergies and asthma was significantly protective for the three different kinds of brain tumors examined in the study. Individuals with the disorders had a 35 percent reduced risk of developing GBM, a 51 percent reduced risk of AA, and a 36 percent reduced risk of LGG.
They also found that participants who used antihistamines were more likely to develop brain tumors. Participants who used antihistamines had three times the risk of developing an AA tumor and two times the risk of developing LGG, compared to those who did not use antihistamines. The risk of developing a GBM was also increased by 26 percent, but that was not statistically significant, the researchers say.
"This suggests that among people who are susceptible, those who have allergies and don't do anything about it may be protected to some degree against brain tumors," Bondy says. "But those who use antihistamines could decrease that protection and increase their risk. The real question is if there are particular gene variants that would make a person susceptible."
The researchers also asked participants about their history of chicken pox. A latent infection is known to promote low level inflammation in the brain, which could also provide an immune response that protects against tumor development. They found that a history of chicken pox significantly reduced the risk of developing AA tumors. The risk of developing the other two kinds of tumors studied was also reduced (40 percent for GMB and 22 percent for LGG), but not significantly so.
Finally, the researchers looked at use of anti-inflammatory (Cox-2 inhibitors) drugs among study participants and found a significant reduction (31 percent) in development of GBM among those who used them.
"There are three pathways that lead to inflammation in the brain, and reducing one with a Cox-2 inhibitor may be beneficial," Bondy says.
"These are all interesting signals that may give us a clue as to the role of inflammation and development of different kinds of brain tumors," Scheurer says. "We will need much more epidemiological and genetic data to make any firm conclusions and are collaborating with other institutions to pull that information together."