Familial risks in nervous-system tumours: a histology-specific analysis from Sweden and Norway.
BACKGROUND
There are limited data available on tumour subtype-specific familial risks for nervous-system tumours. We aimed to provide such data at the population level.


METHODS
We used data from the nationwide Swedish and Norwegian databases on familial cancer to calculate standardised incidence ratios (SIRs) for the familial risk of developing a nervous-system tumour in offspring born after 1931 (Sweden) or 1900 (Norway) whose parents or siblings were probands.


RESULTS
54 195 patients had nervous-system tumours, 22 331 of whom belonged to the offspring generation aged 0-72 years in Sweden and 0-51 years in Norway. Of 709 familial patients in the offspring generation, 438 (61.8%) had a parent affected by a nervous-system tumour (SIR 1.66; 95% CI 1.51-1.82), 236 (33.3%) had a sibling affected by a nervous-system tumour (SIR 2.01; 95% CI 1.76-2.28), and 35 (4.9%) belonged to families with a parent and at least two siblings affected by a nervous-system tumour (multiplex families; SIR 13.40; 95% CI 9.33-18.66). The SIR for glioma was 1.8 (1.5-2.0) when a parent was a proband, but increased to 11.2 (5.7-19.5) in multiplex families. Early-onset neurinoma and haemangioma showed high familial risks; with an SIR for neurinoma of 1.7 (1.4-2.2) for offspring of affected parents, 2.7 (2.0-3.5) for siblings, and 27.2 (13.5-48.8) for multiplex families, and an SIR for haemangioma of 2.4 (1.4-3.8) for offspring of affected parents. Histology-specific population-based familial risks were shown for meningioma (1.6 for offspring of affected parents; 95% CI 1.3-2.0), ependymoma (2.7 for young offspring <20 years; 1.1-5.5), medulloblastoma (4.1 for siblings; 1.7-8.1), and neuroblastoma (3.2 for siblings; 1.1-6.9).


CONCLUSIONS
Our results suggest a complex genetic background for nervous-system tumours, which differs depending on the age of onset and histological subtype of the tumour. High sibling risks might suggest recessive inheritance. As the high-penetrant multiplex families only accounted for about 5% of familial nervous-system tumours, most familial cases are probably caused by low-penetrance genes.


BACKGROUND
The Nordic Cancer Union, Deutsche Krebshilfe, the Swedish Cancer Society, and the Swedish Council for Working Life and Social Research.
Hemminki
Kari
K
Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. k.hemminki@dkfz.de
Tretli
Steinar
S
Sundquist
Jan
J
Johannesen
Tom B
TB
Granström
Charlotta
C
D000328:Adult; D017668:Age of Onset; D000368:Aged; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D009423:Nervous System Neoplasms / Q000453:epidemiology / Q000235:genetics*; D009664:Norway / Q000453:epidemiology; D010290:Parents; D035781:Siblings; D013548:Sweden / Q000453:epidemiology; D055815:Young Adult