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Younger Siblings May Boost Brain Tumor Risk

The link might be infections passed on in adolescence, researchers say

TUESDAY, Dec. 12, 2006 (HealthDay News) -- Can the number of brothers and sisters you have affect your risk of developing a brain tumor?

Possibly, German researchers report. They found that children with three or more younger siblings face two to four times the risk of developing a brain tumor by age 15 compared to children with no siblings.

This risk was not seen in children with three or more older siblings or in adults who grew up in large families, however.

"The association with number of younger siblings, and not with number of older siblings, suggests that infections or re-infections in late childhood may play an important role in the development of pediatric nervous system tumors," said lead researcher Dr. Andrea Altieri, of the German Cancer Research Center in Heidelberg, Germany. The findings are published in the Dec. 12 issue of Neurology.

The population-based study, which Altieri called the largest of its kind, analyzed more than 13,600 Swedish brain tumor cases.

It found that children with three or more younger siblings had twice the risk of nervous system tumors known as neuroblastomas, more than twice the risk of brain cancers such as medulloblastoma or ependymoma, and nearly a quadruple risk of meningioma (cancer of the brain's lining, the meninges) compared to children with no siblings.

"The association between the number of siblings and other measures of child overcrowding and the risk of infections is well-documented," Altieri said. "The strongest evidence comes from several studies showing that children attending day-care centers have a two- to fourfold increased risk of infection compared to children cared for at home."

But how would the age of siblings influence brain tumor risk? Altieri has a theory.

"When you have many younger siblings, you have a higher risk of infection during early adolescence and a higher risk of being re-infected from your younger siblings," the researcher pointed out.

On the other hand, the presence of many older siblings increases the risk of infection in infancy and early childhood. "As has been reported for other childhood malignancies, very early infection could even be protective against nervous system tumors," Altieri said, which could explain why no increased risk was seen in children with three or more older siblings.

"There is growing evidence that specific viral infections are associated with several types of cancer," Altieri said, citing links between the Epstein-Barr virus and Hodgkin's lymphoma, human papillomavirus (HPV) and cervical cancer, hepatitis C virus and liver cancer, and HIV and Kaposi's sarcoma.

Although there may be a link between childhood infections and brain tumors, Altieri points out that there's still no proof that infections actually cause them. "Any attempt to show a causal association should selectively consider child nervous system tumors and take into account not only the type of infection but also the individual frequency of childhood infections, the age of infections and the persistency of infections," the researcher said.

"This is a large, well-done study," said Dr. Paul Graham Fisher, of Stanford University in Palo Alto, Calif. "It puts out the idea that maybe there's an issue with birth order and brain tumors, which is interesting. It also points to the fact that we don't have a good understanding of how the immune system, for good or ill, influences the development of brain tumors."

But Fisher said that the study's suggestion that infections may play a role in brain-tumor development has been contradicted by other recent epidemiological research. "A lot of folks have either abandoned or pooh-poohed the idea that brain tumors in kids are virally mediated," he said. "This study should have been put in the context of prior studies that really haven't panned out."

Fisher also faulted the researchers not considering other possible reasons why children with younger siblings are at increased risk. "Maybe it's because Scandinavian people have more children after the first one is diagnosed with a brain tumor," he said. "So, there could be a selection bias here."

Altieri said that several small studies involving fewer than 100 cases have investigated an association between different types of infections -- such as influenza during pregnancy and polyoma virus infection in childhood -- and the subsequent risk of brain tumors. "The results have been inconsistent," the researcher said. However, "this does not mean that infections are not associated with these malignancies."

Altieri allowed that other factors may account for an increased risk of brain tumors. "So far, the association of nervous system tumors with other socioeconomic factors has been very inconsistent. However, we cannot rule out the possibility that other socioeconomic correlates are associated with the disease."

More information

To learn more about primary brain tumors, visit the National Library of Medicine.

SOURCES: Andrea Altieri, DS.C., German Cancer Research Center, Heidelberg, Germany; Paul Graham Fisher, M.D., associate professor, neurology, pediatrics, and neurosurgery and human biology, and the Beirne Family Director of Neuro-Oncology, Stanford University, Palo Alto, Calif; Dec. 12, 2006, Neurology.
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