There are estimated to be 13 distinct hereditary renal cell carcinoma (RCC) syndromes, each of which is associated with specific germline mutations, including von Hippel-Lindau disease (VHL).1 VHL is a rare autosomal dominant cancer syndrome occurring in people with germline mutations in the VHL gene. VHL occurs in approximately 1 in 36,000 live births2 and is the most common cause of inherited clear cell RCC.3

By age 60, as many as 70% of patients with VHL will develop RCC, and it is the leading cause of mortality in patients with VHL. Patients with VHL can undergo serial imaging of the kidney to screen for RCC, which can be asymptomatic for long periods of time. Abdominal computed tomography is typically the most reliable imaging modality for diagnosing renal lesions in patients with VHL, and allows clinicians to differentiate between simple and more complex renal cysts.

Unfortunately, there are no other reliable methods to predict which patients with VHL will progress to RCC, or at what age RCC may present, even within families with a history of the disease.

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A recent study published in Cancer Medicine tested whether shorter blood telomere length could serve as a new biomarker for age-related tumor risk in patients with VHL.

“Telomere shortening has been proved to be a risk factor in many sporadic and hereditary cancers, including Lynch syndrome, hereditary prostate cancer, familial, and sporadic ovarian cancer,” wrote Jiang-Yi Wang, of Peking University First Hospital, Beijing, China, and colleagues.

Wang and colleagues conducted a study that included 300 Chinese patients with VHL and 92 healthy family controls. Blood telomere length was measured in 184 patients with VHL and all controls.

Telomere length was significantly shorter in patients with VHL compared with the healthy controls (P = .0183). A positive correlation was found between telomere length and the age of onset of 5 major tumors, including RCC. In addition, multivariable analysis showed that patients with shorter telomere length had a higher age-related risk for RCC (hazard ratio = 2.13; 95% CI, 1.33-3.39; P = .002).

“This [finding] indicates that shortened telomeres resulting in genomic instability may contribute to the genetic alteration of the wild-type allele, which accelerates malignant transformation of normal cells,” Wang and colleagues wrote. “Our findings indicate that shorter telomere length is a new biomarker for tumor risks in VHL patients, which is useful for genetic counseling and prompts future research about the role of telomere shortening in the pathogenesis of VHL-associated tumors.”


  1. Giles RH, Choueiri TK, Heng DY, et al. Recommendations for the management of rare kidney cancers. Eur Urol. 2017. [Epub ahead of print] doi: 10.1016/j.eururo.2017.06.040
  2. Varshney N, Kebede AA, Owusu-Dapaah H, et al. A review of von Hippel-Lindau syndrome. J Kidney Cancer VHL. 2017;4(3):20-29. doi: 10.15586/jkcvhl.2017.88
  3. Woodward ER, Ricketts C, Killick P, et al. Familial non-VHL clear cell (conventional) renal cell carcinoma: clinical features, segregation analysis, and mutation analysis of FLCN. Clin Cancer Res. 2008;14(18):5925-5930. doi: 10.1158/1078-0432.CCR-08-0608
  4. Wang JY, Peng SH, Ning XH, et al. Shorter telomere length increases age-related tumor risks in von Hippel-Lindau disease patients. Cancer Med. 2017. [Epub ahead of print] doi: 10.1002/cam4.1134