Brain cancer starts in one of two ways: either cells inside the brain itself begin growing out of control, or cancer from somewhere else in the body spreads to the brain. The second type, called metastatic or secondary brain cancer, is roughly four times more common than tumors that originate in the brain. Understanding which type you’re dealing with matters because the origin shapes everything about how the cancer behaves and how it’s treated.
Primary Brain Tumors: Cancer That Starts in the Brain
Primary brain tumors grow from the brain’s own cells. The most common and aggressive form, glioblastoma, arises from glial cells, the support cells that surround and protect neurons. For a long time, scientists assumed each type of brain tumor came from a specific cell type: tumors that looked like they involved star-shaped cells called astrocytes were thought to come from astrocytes, while tumors involving insulation-producing cells called oligodendrocytes were thought to come from oligodendrocyte precursors. Research has complicated that picture. Studies in mice have shown that astrocytes alone, given the right genetic disruption, can give rise to both astrocytomas and oligodendrogliomas, as well as mixed tumors containing features of both.
What actually triggers these cells to become cancerous comes down to specific genetic errors. In glioblastoma, 70 to 80% of tumors carry a mutation in a gene called TERT, which controls how long a cell can keep dividing. Normally, cells have a built-in limit on how many times they can replicate before they stop and die. TERT mutations override that limit, essentially making the cell immortal. Another key mutation involves a gene called IDH, which controls how cells process energy. When IDH mutates, it produces a chemical that accumulates inside the cell and silences tumor-suppressing genes, the very genes designed to stop uncontrolled growth. IDH mutations show up in 70 to 80% of lower-grade gliomas (slower-growing tumors) but only about 10 to 12% of glioblastomas.
These mutations don’t happen because of a single identifiable cause in most people. They accumulate over a lifetime, sometimes randomly during normal cell division.
Secondary Brain Tumors: Cancer That Spreads From Elsewhere
Most brain cancers didn’t start in the brain at all. They’re colonies established by cancer cells that traveled from a tumor in another organ. Lung cancer is by far the leading source, accounting for about 77% of all brain metastases. After lung cancer, the next most common origins are melanoma (4.2%), breast cancer (3.8%), kidney cancer (3.1%), and colorectal cancer (1.5%).
Getting into the brain is not easy for a traveling cancer cell. The brain is protected by the blood-brain barrier, a tightly sealed layer of cells lining the blood vessels that prevents most substances from crossing into brain tissue. Cancer cells breach this barrier using specific tools. Research has identified an enzyme called MMP9 as a central player: cancer cells use it to loosen the connections between the cells of the blood-brain barrier, creating gaps they can slip through. When researchers blocked MMP9 in lab experiments, cancer cell penetration across the barrier dropped significantly and fewer micro-colonies formed. Interestingly, MMP9 doesn’t seem to work by breaking down the structural scaffolding around blood vessels, as scientists initially expected. Instead, it appears to disrupt the cell-to-cell signaling that keeps the barrier sealed.
Known Risk Factors
The only environmental exposure with strong, consistent evidence linking it to brain cancer is ionizing radiation. This includes radiation therapy directed at or near the head, particularly when received during childhood. Data from atomic bomb survivors shows that people exposed at age 10 had a significantly elevated risk of developing brain tumors later in life, while those exposed at age 40 had a much smaller, statistically uncertain increase. The younger the brain, the more vulnerable it appears to radiation-induced damage.
Cell phones are probably the risk factor people wonder about most. The largest prospective study on the topic, the COSMOS study tracked by the International Agency for Research on Cancer, found that people with the highest lifetime hours of mobile phone calls did not have a higher rate of brain tumors compared to light users. The current weight of evidence does not support a link between mobile phone use and brain cancer.
Inherited Genetic Conditions
A small percentage of brain tumors are tied to inherited syndromes that run in families. These conditions don’t guarantee a brain tumor will develop, but they significantly raise the odds. The most recognized include:
- Li-Fraumeni syndrome: caused by mutations in the TP53 gene, one of the body’s most important tumor suppressors. People with this syndrome face elevated risks of multiple cancer types, including brain tumors.
- Neurofibromatosis (types 1 and 2): caused by mutations in the NF1 or NF2 genes. These conditions cause abnormal growths along nerves and increase the risk of certain brain and spinal tumors.
- Tuberous sclerosis: caused by mutations in TSC1 or TSC2 genes, leading to benign growths in multiple organs including the brain, some of which can become problematic.
- Turcot syndrome: caused by mutations in DNA repair genes, linking colon polyps with brain tumors.
Together, these syndromes account for a minority of all brain tumor cases. Most people diagnosed with a brain tumor have no family history of one.
How Brain Tumors Differ by Age
The types of brain tumors that develop, and where they grow, vary significantly between children and adults. In children, tumors tend to form in the back and lower parts of the brain. The most common childhood brain tumor, pilocytic astrocytoma, appears in the cerebellum about 70% of the time. When that same tumor type occurs in adults, it’s more likely to grow in the upper brain. Medulloblastoma follows a similar pattern: in children it typically grows along the brain’s midline and blocks fluid drainage, causing pressure buildup. In adults, it more often appears in the side of the cerebellum and causes balance and coordination problems instead.
Some tumor types have a bimodal pattern, appearing in two distinct age groups. Craniopharyngiomas, for example, peak between ages 5 and 14, then peak again between ages 50 and 70. The childhood and adult versions even involve different subtypes of the same tumor.
Overall Survival and Outlook
Brain cancer as a whole is relatively rare, occurring at a rate of about 6.1 new cases per 100,000 people per year in the United States. The overall five-year survival rate across all types is 33%, but that number masks enormous variation. Low-grade gliomas with IDH mutations tend to grow slowly and carry a much better prognosis than glioblastoma, which remains one of the most difficult cancers to treat. Tumors caught while still confined to their original site have a five-year survival rate of about 35%, while those that have spread to nearby tissue drop to around 21%.
The molecular profile of a tumor now matters as much as, or more than, what it looks like under a microscope. Since 2021, the World Health Organization classifies brain tumors based on their genetic mutations, not just their appearance. A tumor that looks like a glioblastoma under the microscope but carries an IDH mutation is now classified differently, because it behaves differently and responds differently to treatment. This shift means two patients with tumors that look identical could receive very different diagnoses and treatment plans based on the genetic fingerprint of their cancer.