Relatives of patients with brain tumors seen to be at increased risk

NEW YORK (Reuters Health) - By linking a Utah genealogy database to statewide cancer records, researchers have uncovered evidence of a familial contribution to primary brain cancer risk.

"There has been landmark work done previously using the Utah Population Data Base resource, in discovering hereditary associations and specific genes for breast cancer, colon cancer and other non-neoplastic diseases," Dr. Deborah T. Blumenthal told Reuters Health. "We sought to utilize this unique resource to search for familial relationships in primary brain tumors."

The database includes over 2 million persons with up to 10 generations of genealogical data. Dr. Blumenthal, currently at Tel-Aviv Sourasky Medical Center in Israel, and Dr. Lisa A. Cannon-Albright at the University of Utah in Salt Lake City examined the risk of brain tumors in the relatives of 744 individuals with astrocytoma, 658 patients with glioblastoma, and 1 patient with both.

According to their report in the September 23 issue of Neurology, significant excess risk exists among first-degree relatives of patients with astrocytoma (RR = 3.82, p = 0.0004) or glioblastoma (RR = 2.29, p = 0.026), compared with the rate of disease in the general population.

There was also significantly increased risk among second-degree relatives of patients with astrocytoma (RR = 1.91, p = 0.03).

Noting that cancers with a genetic contribution often occur at an earlier age than sporadic cases, the researchers report that first degree relatives of patients diagnosed before age 20 years were at higher risk (RR = 6.44, p = 0.004). Risk was also elevated for family members of cases with astrocytoma diagnosed before age 15 (RR = 9.65, p = 0.004).

"These findings, which remained significant beyond first-degree relations, support the hypothesis of familiality -- a common gene or group of genes that may predispose individuals to brain tumors," Dr. Blumenthal said.

"It needs to be stressed that we are still considering a very small minority (less than 5%) of an already small group of patients (less than 20,000/year in the US) who may have a familial risk for being affected with these tumors," she added. "However, clinicians should be aware of this association and carefully query family history in their patients. If other family members have neurologic symptoms, the threshold for screening them for a brain tumor should be lower."

Such symptoms, she explained, may include "new, progressive headaches; nausea or vomiting; seizures (which may be motor or sensory phenomenon, or even episodes of odd smells/tastes or deja vu, when the temporal lobe is involved); changes in vision; changes in speech or language ability (word-finding difficulty); changes in personality (including apathy or apparent depression); imbalance or incoordination."

The researchers now plan prospective follow-up of these high risk pedigrees.

"If genes or loci responsible for brain tumors could be identified, they could have relevance not only for familial tumors, but for the larger population as well," Dr. Blumenthal concluded. "Ultimately, with such information, screening and even preventive therapy for malignant brain tumors might be possible in the future."

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