Article Text
Abstract
Background Historically, the survival of patients with von Hippel-Lindau disease (vHL) has been poorer than that of the general population. We aimed to determine whether the survival of VHL mutation carriers and their risk of vHL-related death has changed over time and how it has been affected by sex, genotype and surveillance attendance.
Methods In a retrospective cohort study, we included all known Danish vHL families with a VHL mutation. We assessed the survival and causes of death for 143 VHL mutation carriers using Cox regression models and compared vHL survival with that of 137 siblings without vHL. vHL life expectancy was compared with the general population using a relative survival model.
Results The estimated mean life expectancies for male and female patients born in 2000 were 67 and 60 years, respectively. Survival is influenced by the sex and genotype of the patient. Female patients have a significantly higher risk of vHL-related death than male patients (HR=2.25, 95% CI 1.20 to 4.20, p=0.011). Overall, 79% (53 of 67) of deaths were vHL-related, but the risk of vHL-related death has decreased over time, as has the frequency of renal cell carcinoma (RCC)-related death. Surveillance is especially beneficial for truncating mutation carriers, who have the greatest RCC and central nervous system (CNS) hemangioblastoma risk.
Conclusions vHL survival has improved over time and has become closer to that of siblings without vHL and the general population. Even though the risk of vHL-related death has decreased significantly, the main cause of death is still CNS hemangioblastomas and hence improved treatment options are essential.
- von Hippel-Lindau disease
- Clinical genetics
- Survival
- Life expectancy
- Surveillance
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Footnotes
Contributors MLB and AMJ had the idea for the study. MLB and MLMB initiated the study and designed the overall study structure. EB-J, MLMB and MLB together planned the statistical analyses, which were performed by EB-J. AMJ and MLMB interviewed the participating subjects, collected and evaluated their medical records and register data. MLMB recorded the events of interest and sorted the data. MLB monitored the data collection. All authors interpreted the results. MLMB drafted the first version of the manuscript; EB-J drafted the section describing the statistical methods. All authors critically revised the draft paper and approved the final version of the manuscript.
Funding The study was financially supported by the Danish Cancer Society (R20-A968-10-S2), the Lundbeck Foundation (R48-A4839), Anna and Hans Steffensen's Foundation to support Danish Cancer Research and the Danish association of patients with vHL and their relatives.
Competing interests None declared.
Ethics approval The Danish Regional Committees on Biomedical Research Ethics for the Capital region of Denmark (H-2-2010-012).
Provenance and peer review Not commissioned; externally peer reviewed.