Genetic predisposition to kidney cancer

Semin Oncol. 2016 Oct;43(5):566-574. doi: 10.1053/j.seminoncol.2016.09.001. Epub 2016 Sep 22.


Kidney cancer is not a single disease but is made up of a number of different types of cancer classified by histology that are disparate in presentation, clinical course, and genetic basis. Studies of families with inherited renal cell carcinoma (RCC) have provided the basis for our understanding of the causative genes and altered metabolic pathways in renal cancer with different histologies. Von Hippel-Lindau disease was the first renal cancer disorder with a defined genetic basis. Over the next two decades, the genes responsible for a number of other inherited renal cancer syndromes including hereditary papillary renal carcinoma, Birt-Hogg-Dube´syndrome, hereditary leiomyomatosis and renal cell carcinoma, and succinate dehydrogenase-associated renal cancer were identified. Recently, renal cell carcinoma has been confirmed as part of the clinical phenotype in individuals from families with BAP1-associated tumor predisposition syndrome and MiTF-associated cancer syndrome. Here we summarize the clinical characteristics of and causative genes for these and other inherited RCC syndromes, the pathways that are dysregulated when the inherited genes are mutated, and recommended clinical management of patients with these inherited renal cancer syndromes.

Keywords: Birt-Hogg-Dubé syndrome; Hereditary leiomyomatosis and renal cell carcinoma; Hereditary papillary renal carcinoma; Inherited renal cancer syndromes; Kidney neoplasms; Von Hippel-Lindau.

Publication types

  • Review

MeSH terms

  • Genetic Predisposition to Disease*
  • Humans
  • Kidney Neoplasms / etiology
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / therapy
  • Mutation
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-met / genetics
  • Succinate Dehydrogenase / genetics
  • Tuberous Sclerosis / genetics
  • Tumor Suppressor Proteins / genetics
  • Von Hippel-Lindau Tumor Suppressor Protein / genetics


  • FLCN protein, human
  • Proto-Oncogene Proteins
  • SDHD protein, human
  • Tumor Suppressor Proteins
  • Succinate Dehydrogenase
  • Von Hippel-Lindau Tumor Suppressor Protein
  • MET protein, human
  • Proto-Oncogene Proteins c-met
  • VHL protein, human