Parental age and risk of genetic syndromes predisposing to nervous system tumors: nested case–control study
Received 7 December 2017
Accepted for publication 12 March 2018
Published 20 June 2018 Volume 2018:10 Pages 729—738
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Cristina Weinberg
Peer reviewer comments 3
Editor who approved publication: Professor Vera Ehrenstein
Maral Adel Fahmideh,1 Giorgio Tettamanti,1 Catharina Lavebratt,2 Mats Talbäck,1 Tiit Mathiesen,3,4 Birgitta Lannering,5 Kimberly J Johnson,6,7 Maria Feychting1
1Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; 2Neurogenetics Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden; 3Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; 4University of Copenhagen, Copenhagen, Denmark; 5Department of Pediatrics, University of Gothenburg, Gothenburg, Sweden; 6Brown School, Washington University in St Louis, St Louis, MO, USA; 7Department of Pediatrics, School of Medicine, Washington University in St Louis, St Louis, MO, USA
Purpose: Phacomatoses are genetic syndromes that are associated with increased risk of developing nervous system tumors. Phacomatoses are usually inherited, but many develop de novo, with unknown etiology. In this population-based study, we investigated the effect of parental age on the risk of phacomatoses in offspring.
Patients and methods: The study was a population-based nested case–control study. All individuals born and residing in Sweden between January 1960 and December 2010 were eligible for inclusion. Using the Patient Register, 4625 phacomatosis cases were identified and further classified as familial or nonfamilial. Ten matched controls per case were randomly selected from the eligible population. Data were analyzed using conditional logistic regression. Analyses were conducted for neurofibromatosis alone (n=2089) and other phacomatoses combined (n=2536).
Results: Compared with offspring of fathers aged 25–29 years, increased risk estimates of nonfamilial neurofibromatosis were found for offspring of fathers aged 35–39 years (odds ratio [OR]=1.43 [95% CI 1.16–1.74]) and ≥40 years (OR =1.74 [95% CI 1.38–2.19]). For other nonfamilial phacomatoses, the risk estimate for offspring of fathers aged ≥40 years was OR =1.23 (95% CI 1.01–1.50). Paternal age was not associated with familial phacomatoses, and no consistent association was observed with maternal age.
Conclusion: The findings show a consistent increase in risk of de novo occurrence of phacomatoses predisposing to nervous system tumors in offspring with increasing paternal age, most pronounced for neurofibromatosis, while maternal age did not seem to influence the risk. These findings suggest an increasing rate of new mutations in the NF1 and NF2 genes in spermatozoa of older fathers.
Keywords: phacomatoses, nervous system tumor predisposition syndromes, parental age, registry, neurofibromatosis
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