title: Risk of new tumors in von Hippel-Lindau patients depends on age and genotype.
abstract: OBJECTIVE
  The von Hippel-Lindau (vHL) phenotype is variable, which complicates genetic counseling and surveillance. We describe how the rate of new tumor development varies through the lifetimes of vHL patients and how it is influenced by age and genotype.
  
  
  METHODS
  In a national cohort study, we included 52 VHL mutation carriers who were retrospectively followed for a total of 799 person-years. From birth to current age, 581 manifestations were diagnosed during 2,583 examinations in the study subjects. Manifestation rates were analyzed using Poisson regression and compared in groups of different ages, tumor sites, and genotypes.
  
  
  RESULTS
  The rate of new tumor development varied significantly with age and was highest at 30-34 years (0.4 new tumors/year). Tumor location further influenced the rate. The risk of retinal tumors was highest in subjects during the teenage years but was highest for cerebellar tumors in subjects during their 30s. Truncating VHL mutation carriers had a significantly higher manifestation rate compared with missense mutation carriers (hazard ratio = 1.85, 95% confidence interval: 1.06-3.24, P value = 0.031).
  
  
  CONCLUSIONS
  The rate of new manifestation development is not constant throughout the life span of vHL patients; instead, it varies significantly with age and genotype and depends on anatomical location. Retinal surveillance is crucial during the teenage years, whereas cerebellar surveillance is especially important in adulthood.Genet Med 18 1, 89-97.
authors.affiliation: Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Marie Louise Mølgaard
authors.identifier: http://orcid.org/0000-0003-4214-710X
authors.initials: ML
authors.lastname: Binderup
authors.affiliation: Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark.|Section of Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Esben
authors.initials: E
authors.lastname: Budtz-Jørgensen
authors.affiliation: Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Marie Luise
authors.initials: ML
authors.lastname: Bisgaard
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D015331:Cohort Studies; D005260:Female; D056726:Genetic Association Studies; D005817:Genetic Counseling; D020022:Genetic Predisposition to Disease; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009426:Netherlands; D012189:Retrospective Studies; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics*; D006623:von Hippel-Lindau Disease / Q000175:diagnosis / Q000235:genetics*
chemical_list: D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human
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