NEW YORK (Reuters Health) – A single nucleotide polymorphism in the tumor suppressor TP53 gene appears to be a risk factor for glioblastoma multiforme at an earlier age — before 45 years, a French research team reports in the January 27th issue of Neurology.

The Pro/Pro variant at codon 72 of TP53 “results in stronger transcriptional activation but weaker induction of apoptosis than the arg72 variant,” Dr. Marc Sanson and co-authors explain. Although this polymorphism is associated with various cancers, its impact on glioblastoma is unknown.

Dr. Sanson, at Hopital de la Salpetriere in Paris, and his team analyzed DNA from 254 patients with glioblastoma (ages 19.2 to 83.6 years) and 238 healthy controls (ages 16 to 75 years).

Overall, TP53 codon 72 status did not differ between patients with glioblastoma and control subjects, the authors report, and genotype was not associated with survival.

However, the Pro/Pro genotype occurred significantly more often among patients who were 45 years old (20.6% in 37 cases) compared with older patients (6.4% in 217 cases, p = 0.002) and healthy controls (5.9% in 238 subjects, p = 0.001).

The researchers confirmed the correlation in an independent series of 29 patients who developed glioblastoma before the age of 45. The findings were similar, with Pro/Pro genotype frequency of 17.2%.

“Combining knowledge of an individual’s TP53 genotypes with information on the known DNA repair genes polymorphisms and environmental risk factors may improve risk estimates and help to identify individuals who are genetically susceptible to develop glioblastoma, and at an earlier age,” the authors conclude.

“However,” Dr. Sanson noted in a prepared statement, “the risk of this population remains low, even multiplied by three or four as shown here, because these brain tumors (glioblastomas) are infrequent in young people.”

Reference:
Neurology 2009;72:332-336.