Glioblastoma

Glioblastoma (GBM) is the most common and malignant tumor among the neoplasms of the central nervous system. It originates in the glia cells, responsible for supporting the cells of the nervous system. It is fast growing and can manifest itself at any age, although it is more frequent in adults. Due to their malignancy, they are tumors with a poor prognosis. Its incidence is very low, not exceeding 2-3 cases per 100,000 inhabitants.

The exact causes of glioblastoma are unknown. It may develop from a diffuse astrocytoma or from an anaplastic astrocytoma (secondary glioblastomas), but in most cases it occurs de novo, without any evidence of previous neoplasia.

At the moment, ionizing radiation is the only unequivocal risk factor identified for glial and meningeal tumors. Studies conducted indicate that skull radiation, even at low doses, can increase the risk of glial tumors, with a latency period of up to 20 years after exposure.

Other factors may also contribute to the development of the disease:

  • Diseases of genetic origin that predispose to tumor formation such as neurofibromatosis type 1 and type 2, Lynch syndrome, Turcot syndrome and Li-Fraumeni syndrome.
  • Although it can develop at any time, it is more frequent after 45 years of age.
  • Sex, being somewhat more frequent in men than in women.

Unlike carriers for a few hereditary cancer syndromes, such as Turcot syndrome or Li-Fraumeni syndrome, in which the risk of developing this type of tumor is increased, the genetic factors that may be contributing to the formation of glioblastomas are unknown, although GWAS studies have begun to shed light on this issue. In an association study carried out with almost 12500 patients and more than 18000 controls, 10 loci associated with GBM were identified. Among the genes identified, those involved in the maintenance of telomere length, such as TERT or RTEL1, and the cell cycle regulators EGFR and CDKN2B-AS1, also associated with other types of cancer, stand out.

Symptoms

Because glioblastomas can grow rapidly, the most common symptoms are usually caused by increased pressure in the brain. These symptoms may include headache, nausea, vomiting and drowsiness. In addition, seizures, progressive cognitive dysfunction, personality changes, behavioral changes and memory loss may occur.

Depending on the location of the tumor, patients may develop a variety of symptoms such as weakness on one side of the body, memory loss and/or speech difficulties and visual changes.

Prevention

There is no total preventive measure for the development of glioblastomas, however, in some cases avoiding modifiable risk factors may help to reduce it. At the moment, the only identified risk factor clearly associated with the development of these tumors is exposure to ionizing radiation.

Exposure to this type of radiation can occur by different routes:

  • Internal exposure: occurs when the radionuclide is inhaled, ingested or injected.
  • External exposure: occurs when the radioactive material is present in the environment.
  • The people most exposed to this type of radiation are astronauts (from cosmic radiation), X-ray medical personnel, researchers and radioactive facility personnel. In addition, additional exposures may be received at each X-ray and nuclear medicine examination.

Number of observed variants

13.5 million variants

Number of risk loci analyzed in the study

10 loci

Bibliography

Melin BS, Barnholtz-Sloan JS, Wrensch MR, et al. Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors. Nature Genetics. 2017 May;49(5):789-794.

Louis DN, Perry A, Wesseling P, et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol. 2021 Aug 2;23(8):1231-1251.

American Cancer Society [April 2022]

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