Pathogenesis (development of disease)
Brain tumors are mostly neuroepithelial in origin. The exact cause of brain tumors is ultimately not yet clear.A genome-wide association study (GWAS) of the most common malignant brain tumor, glioma, has confirmed the histopathologic bifurcation that separates “high-grade” glioblastoma from other “low-grade” gliomas.
Etiology (Causes)
Biographic causes
- Genetic burden from parents, grandparents (only about 1-5% of gliomas are hereditary/inherited)
- Genetic risk depending on gene polymorphisms, related to gliomas (a type of brain tumor, formed from glial cells (supporting cells of nervous tissue)):
- Genes/SNPs (single nucleotide polymorphism):
- Genes: CDKN2B-AS1, PARP1, TERT.
- SNP: rs55705857 in an intergenic region.
- Allele constellation: AG (6.0-fold).
- Allele constellation: GG (> 6.0-fold)
- SNP: rs4977756 in the CDKN2B-AS1 gene.
- Allele constellation: AG (1.39-fold).
- Allele constellation: GG (1.93-fold)
- SNP: rs4295627 in an intergenic region.
- Allele constellation: GT (1.36-fold).
- Allele constellation: GG (1.85-fold)
- SNP: rs2736100 in the gene TERT
- Allele constellation: GT (1.27-fold).
- Allele constellation: GG (1.61-fold)
- SNP: rs1136410 in the gene PARP1
- Allele constellation: CT (0.80-fold).
- Allele constellation: CC (<0.80-fold)
- Genes/SNPs (single nucleotide polymorphism):
- Genetic risk dependent on gene polymorphisms, related to meningiomas (tumors that do not grow in brain tissue but originate in the meninges):
- Genes/SNPs (single nucleotide polymorphism; English : single nucleotide polymorphism):
- Genes: BRIP1, MILLT10, MTRR.
- SNP: rs4968451 in the gene BRIP1
- Allele constellation: AC (1.61-fold).
- Allele constellation: CC (2.33-fold)
- SNP: rs11012732 in the gene MILLT10
- Allele constellation: AG (1.4-fold).
- Allele constellation: GG (2.0-fold)
- SNP: rs1801394 in the gene MTRR
- Allele constellation: GG (1.4-fold).
- Genes/SNPs (single nucleotide polymorphism; English : single nucleotide polymorphism):
- Genetic risk depending on gene polymorphisms, related to gliomas (a type of brain tumor, formed from glial cells (supporting cells of nervous tissue)):
- Developmental malformations
- High birth weight (≥ 4,000 g) – association with astrocytomas.
- Education – at least three years of a university education – versus school career completed after nine compulsory years – leads to a higher probability of glioma occurrence:
- 19% for men
- Women: 23 %
- Hormonal factors
Behavioral causes
- Psycho-social situation
- High earnings – in men, risk increase for glioma by 14%.
- Overweight (BMI ≥ 25; obesity); higher likelihood of developing meningioma:
- BMI 25-29.9: 21%
- BMI ≥ 30: 54
Disease-related causes
Infectious and parasitic diseases (A00-B99).
- Oncogenic viruses
Neoplasms – tumor diseases (C00-D48)
- Brain metastases (metastases/daughter tumors, symptomatic) – up to 20% of cases; mainly in bronchial carcinoma (lung cancer), breast carcinoma (breast cancer), malignant (malignant) melanoma (black skin cancer; highest prevalence (disease frequency) for cerebral metastasis/up to 70% in autopsy studies), renal cell carcinoma, lymphoma, prostate carcinoma (prostate cancer), gastrointestinal neoplasms, thyroid carcinoma; in 3-10% of cases, the primary tumor is unknown
- Primary central nervous system lymphomas (PZNSL) – 2 to 4% of all primary brain tumors; aggressive brain tumors.
Environmental exposures – intoxications (poisonings).
- Carcinogens
- Ionizing rays
Drugs
- Zolpidem (hypnotic/sleep aid) – incidence (frequency of new cases) of benign (benign) brain tumors higher (duration of ingestion: > 2 months of zolpidem; highest risk for benign brain tumors: zolpidem exposure of ≥ 520 mg/year).
Radiotherapy
- After computed tomography (CT) of the head and neck, the risk of tumors in children is increased. This is especially true for thyroid carcinomas (increased by 78%) and brain tumors (increased by 60%). The overall cancer incidence is increased by 13%.
Further
- Cell phone use (cell phones; fixed wireless devices) – statistically significant risk for glioma with cell phone use >1 year; esp. high risk was with exposure before age 20 years