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. Findings: 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). Interpretation: 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. Funding: The Nordic Cancer Union, Deutsche Krebshilfe, the Swedish Cancer Society, and the Swedish Council for Working Life and Social Research.