Glioblastoma (GBM) is a highly aggressive and common brain cancer. It develops from glial cells, supportive cells found in the brain and spinal cord. Classified as a Grade IV tumor, it grows rapidly and is invasive. Though the most frequent malignant brain tumor, it is rare, affecting 3 to 5 people per 100,000 annually. This article explores whether glioblastoma is hereditary.
Is Glioblastoma Directly Inherited?
Most glioblastoma cases are sporadic, meaning they arise without a clear inherited genetic predisposition. Over 90% are not directly passed down from parent to child. Instead, these tumors typically develop due to somatic mutations, which are genetic alterations occurring in individual cells during a person’s lifetime, rather than being inherited from birth.
These acquired genetic changes accumulate within brain cells, contributing to uncontrolled tumor growth. While genetic mutations are fundamental to glioblastoma development, they are usually acquired throughout life. Germline mutations, inherited from parents and present in all cells, account for a very small fraction of glioblastoma occurrences, highlighting the non-hereditary nature of most cases.
Genetic Syndromes Linked to Increased Risk
While glioblastoma is rarely inherited, certain rare genetic syndromes can increase an individual’s susceptibility to various cancers, including glioblastoma. These syndromes involve inherited germline mutations that impair normal cellular processes, such as tumor suppression or DNA repair. For example, Neurofibromatosis Type 1 (NF1) is associated with mutations in the NF1 gene, which regulates cell growth. Individuals with this syndrome have an elevated risk of developing brain tumors, including gliomas.
Li-Fraumeni Syndrome, caused by TP53 gene mutations, significantly increases the risk of multiple cancers, with some individuals developing glioblastoma. The TP53 gene is a tumor suppressor. Turcot Syndrome, involving mutations in genes like APC or MLH1/MSH2 (also linked to Lynch Syndrome), primarily predisposes individuals to colorectal cancer but can also increase the risk of brain tumors, including glioblastoma. Even with these syndromes, glioblastoma remains uncommon, but the genetic predisposition elevates risk compared to the general population.
Other Factors Contributing to Glioblastoma Development
Beyond rare genetic syndromes, other factors contribute to glioblastoma development unrelated to inherited genes. Age is the most significant risk factor, with incidence increasing substantially in older adults, peaking around 64 years. The likelihood of developing the tumor rises with advancing age.
Exposure to high doses of ionizing radiation, particularly from prior radiation therapy, is another established risk factor. This exposure can induce DNA damage contributing to tumor formation years later. Research continues to investigate other potential environmental or lifestyle factors, but evidence remains inconclusive.
Considerations for Genetic Counseling and Testing
Genetic counseling and testing may be considered for individuals or families with concerns about glioblastoma risk. This is recommended when there is a strong family history of cancers consistent with a known hereditary cancer syndrome. Additionally, if a glioblastoma tumor exhibits molecular characteristics suggesting an underlying inherited syndrome, genetic evaluation might be warranted.
A genetic counselor assesses an individual’s personal and family medical history to determine the likelihood of inherited predisposition. They provide information about the implications of genetic testing, including benefits and limitations, and guide individuals through the decision-making process. Due to glioblastoma’s low hereditary component, routine genetic testing is not recommended for all patients or their family members.