TY - JOUR

T1 - Survival and causes of death in patients with von Hippel-Lindau disease

AU - Binderup, Marie Louise Mølgaard

AU - Jensen, Annette Møller

AU - Budtz-Jørgensen, Esben

AU - Bisgaard, Marie Luise

PY - 2017

Y1 - 2017

N2 - 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 vHLrelated death has decreased significantly, the main cause of death is still CNS hemangioblastomas and hence improved treatment options are essential.

AB - 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 vHLrelated death has decreased significantly, the main cause of death is still CNS hemangioblastomas and hence improved treatment options are essential.

U2 - 10.1136/jmedgenet-2016-104058

DO - 10.1136/jmedgenet-2016-104058

M3 - Journal article

C2 - 27539272

AN - SCOPUS:84983503756

VL - 54

SP - 11

EP - 18

JO - Journal of Medical Genetics

JF - Journal of Medical Genetics

SN - 0022-2593

IS - 1

ER -