Brain, other CNS and intracranial tumours risk factors

The estimated lifetime risk of being diagnosed with brain, other CNS and intracranial tumours is nearly 1 in 66 (2%) for females, and 1 in 74 (1%) for males born in 1961 in the UK. [1]

These figures take account of the possibility that someone can have more than one diagnosis of brain, other CNS and intracranial tumours in their lifetime ('Adjusted for Multiple Primaries' (AMP) method).[2]

3% of brain and other CNS tumour (ICD-10 C70-C72) cases in the UK are preventable.[1] The proportion of lifestyle-associated benign and uncertain behaviour brain and other CNS tumours, and other intracranial tumours, has not been estimated.

Brain and other CNS cancer risk is associated with a number of risk factors.[2,3]

Brain and Other CNS Cancer Risk Factors

International Agency for Research on Cancer (IARC) classification. World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) classification does not include brain, other CNS and intracranial tumours because they are not generally recognised to have a relationship to food, nutrition, and physical activity.

International Agency for Research on Cancer (IARC) classifies the role of this risk factor in meningioma development.[1] 2% of brain and other CNS tumour cases in the UK are caused by overweight and obesity.[2]

Meningioma risk is 60% higher in women who are obese (body mass index [BMI] 30+), compared with those of a normal weight (BMI 18.5-24.9), a meta-analysis showed.[3] Meningioma risk in men is not associated with BMI, a meta-analysis showed.[3] Glioma risk is not associated with BMI meta-analysis showed.[3]

Childhood CNS tumour risk is 14% higher in children born weighing 4kg+, compared with those born lighter, a meta-analysis showed.[4] Astrocytoma risk is 22% higher, and embryonal tumour risk is 16% higher, in children born weighing 4kg+, compared with those born lighter.[4]

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Family history

Having a family history of CNS tumours is associated with increased risk of developing a brain tumour, pooled analyses have shown.[1,2] Having a parent with a CNS tumour is associated with a 70% increased risk of being diagnosed with a brain or CNS tumour oneself, compared with the general population, and having a sibling diagnosed is associated with a doubling of risk.[1,2] 

Those with any first-degree relative (parent, sibling or child) diagnosed with glioma have a 77% increased risk of developing glioma themselves, and a 2.2- to 2.6-fold risk increase if the affected relative is a sibling.[2,3]

Having a parent or sibling with meningioma confers a more than doubled (130% increased) risk of meningioma.[2] 

The magnitude of risk increases associated with family history varies by brain tumour subtype, but small sample sizes for these less common tumours preclude firm conclusions.[2] 

Neurofibromatoses (NF)

Neurofibromatoses (NF)  are a group of genetic conditions in which benign (non-invasive) growths affect the nervous system. NF type 1 (NF1) is thought to affect around 1 in 2,700 live births in the UK, whilst NF type 2 (NF2) affects around 1 in 33,000.[4]

The risk of brain and CNS tumours is at least 23-43 times higher in NF1 patients than in the general population.[5,6] The risk of CNS tumours excluding those in the brain may be considerably higher.[6] Relative risk of brain tumours in NF1 patients increases with patient age.[7] Most NF1-associated brain tumours are gliomas.

Both children and adults with NF1 have an increased risk of astrocytoma, with the tumour grade often higher in adults than children.[7] 5-25% of children with NF1 develop optic pathway gliomas.[7]

NF2 patients are commonly diagnosed with bilateral vestibular schwannomas (acoustic neuromas). These affect 90-95% of NF2 patients, and they are typically benign but can cause hearing impairment.[8] Meningiomas affect 45-58% of NF2 patients, and usually arise at a younger age in these patients than in the general population.[8]

Tuberous sclerosis complex (TSC)

Tuberous sclerosis complex (TSC)  causes benign tumors to grow in the brain and elsewhere. The prevalence of TSC is estimated at around 1 in 25,000.[9,10] Up to 20% of TSC patients develop subependymal giant-cell astrocytomas.[11]

Li-Fraumeni syndrome

Li-Fraumeni syndrome  is a very rare genetic condition associated with increased risk of early-onset brain tumours and other cancer types. Astrocytomas, glioblastomas, medulloblastomas, and choroid plexus carcinomas are the most common brain tumours seen in this population.[12]

Von Hippel-Lindau syndrome

Von Hippel-Lindau syndrome  is thought to occur in around 1 in 43,000 live births in the UK.[2] Haemangioblastomas of the brain or spinal cord occur in 60-80% of people with this condition.[13]

Turner syndrome

Turner syndrome  affects around 1 in 2,000 female live births.[14] The risk of CNS tumours is around 4 times higher for Turner syndrome patients than the general population, with particularly increased risks of meningioma and childhood brain tumours.[15]

Turcot’s syndrome

Turcot’s syndrome is associated with both brain and bowel tumours. Turcot’s syndrome type 1 is associated with early-onset gliomas, whilst type 2 is associated with medulloblastoma.[16]

Gorlin syndrome

Gorlin syndrome  (nevoid basal cell carcinoma) is thought to occur in around 1 in 15,000 live births in the UK.[2] Around 5-10% of people with this condition develop medulloblastomas.[17]

International Agency for Research on Cancer (IARC) classifies the role of this risk factor in cancer development.[1] Less than 1% of brain and other CNS tumour cases in the UK are caused by ionising radiation.[2] Evidence on the effects of ionising radiation came initially from studies of atomic bomb survivors, though more recent studies explore the effects of radiation used to diagnose and treat illness, including X-rays, CT scans and radiotherapy.

Ionising radiation overall generally appears to be more strongly associated with meningioma risk than with glioma risk.[3] The risk of meningioma is increased by 64-510% with each Gray (Gy) of ionising radiation exposure received, data from four cohort studies showed.[3] In one of these studies the effect was not statistically significant.[3] Age at exposure, sex, and time since exposure does not appear to modify the effect of radiation on meningioma risk.[3] The risk of glioma appears to be increased by 8%-56% per Gy, though the upper estimate comes from an atomic bomb survivors study and was not statistically significant.[3] Younger age at exposure confers a stronger effect on glioma risk.[3]

Brain tumour risk is almost tripled in people who received 1-2 CT scans (total average X-ray dose around 60 milligrays (mGy)) during childhood or adolescence, large cohort studies have shown.[4,5]

The average x-ray dose from one head CT scan received up to and including age 20 is 28-44 mGy, depending on age and sex.[4]

People who have ever had dental X-rays taken from the sides of the head (bitewing technique) have double the risk of adult meningioma, a US case-control study showed, though over 90% of both cases and controls had received this type of X-ray.[6]

Radiotherapy for a primary brain tumour (compared with no radiotherapy) was associated with around 55% higher risk of secondary brain tumour, in a study of US patients treated between 1973 and 2002.[7]

People who received radiotherapy for cancer during childhood have a 14-fold higher risk of developing glioma later in life, compared with those who did not receive radiotherapy for their childhood cancer.[8] However this finding, from a large study of British childhood cancer survivors, was not quite statistically significant.[8] Analysing only those children whose primary cancer was in the central nervous system revealed that those treated with radiotherapy (versus those treated without) had a significantly higher risk of subsequent brain tumour.[8]The risk of second primary brain tumour increased linearly with increasing radiotherapy dose, with this effect much stronger for meningioma than glioma.[8]

International Agency for Research on Cancer (IARC) classifies the role radiofrequency electromagnetic fields (including from wireless phones) in glioma and acoustic neuroma development.[1]

Brain tumour risk is not increased in people who are ever-users of mobile phones, meta-analyses of case-control and cohort studies have shown.[2,3] Whereas brain tumour risk is 33% higher in people who have used a mobile phone for 10 years or more [2,3] Firm conclusions are precluded by evidence limitations linked with the relative infancy of mobile phone technology, the relatively small number of cohort studies and the quality of the included studies.[2,3]

Childhood brain tumour risk is not associated with exposure to magnetic fields (from overhead power lines or broadcast transmitters) during childhood, a pooled analysis and cohort study have shown.[4,5]

Brain tumour risk in adults is not associated with occupational exposure to magnetic fields, large cohort studies in the UK and Netherlands have shown.[6,7]

The few workplace exposures for which there is any evidence (albeit very limited) of an association with brain tumour risk - inorganic lead, non-arsenical insecticides, and epichlorohydrin - are thought to account altogether for far less than one per cent of all brain tumour cases in the UK.[1] Meningioma in particular may be associated with lead exposure.[2]