Glioblastoma is caused by genetic changes in brain cells that make them grow out of control, but in most people the exact trigger is unknown.
What directly causes glioblastoma
Glioblastoma develops when cells in the brain or spinal cord acquire DNA mutations that disrupt normal control of cell growth and death. These mutations cause the cells to divide too quickly, live longer than they should, and accumulate into a malignant tumor.
Common changes involve genes that regulate growth signals and cell-cycle control, such as receptor tyrosine kinases (for example, EGFR) and genes involved in telomere maintenance like TERT. Glioblastoma cells often have many more genetic abnormalities than lower‑grade astrocytomas, which helps explain their aggressive behavior.
Known risk factors
For most people, no clear external cause is ever found, but several risk factors are linked to a higher chance of glioblastoma.
- Prior exposure to high‑dose ionizing radiation to the head, such as some types of radiation therapy for other cancers, is a well‑established risk factor. Routine background radiation and MRI scans are not known to raise risk in the same way.
- Increasing age is a strong risk factor; glioblastoma occurs most often in older adults, though it can appear at any age.
Genetic and inherited factors
Most glioblastomas are not inherited and occur “sporadically,” meaning without a strong family pattern. However, a small percentage are associated with rare hereditary syndromes that predispose to multiple cancers.
These include conditions such as neurofibromatosis type 1, Li‑Fraumeni syndrome, Turcot syndrome, Lynch syndrome, and some other DNA‑repair or tumor‑suppressor gene disorders. In these syndromes, mutations in genes like TP53, NF1, APC, and mismatch‑repair genes make it easier for brain cells to accumulate additional cancer‑causing changes.
Possible environmental and lifestyle links
Several environmental exposures have been studied, but evidence is limited and often inconclusive.
- Occupational exposure in industries such as petroleum refining or rubber manufacturing, and contact with some pesticides or solvents, has been reported in some observational studies, but links are weak and not definitive.
- Common lifestyle factors such as most forms of smoking or typical mobile phone use have not shown a consistent, strong causal relationship with glioblastoma in large reviews.
Role of infections and “random chance”
Certain viruses, including cytomegalovirus (CMV), human herpesvirus 6 (HHV‑6), and SV40, have been detected in some glioblastoma tissues, leading to speculation that infection may contribute in a subset of cases. This remains an area of active research, and these infections are not considered proven primary causes on their own.
Many experts think that in numerous patients, glioblastoma arises from random, spontaneous DNA mistakes that accumulate over time in susceptible brain cells without any clear external trigger. That is why, even with known risk factors, it is often impossible to say exactly why a particular person developed glioblastoma.
