Hereditary predisposition to kidney cancer: cancer syndromes, multisystemic disorders, and nephropathies

Kidney cancer (KC) is a common disease characterized by extreme heterogeneity. There are nine known monogenic diseases associated with a significantly elevated KC risk: von Hippel-Lindau disease, MET-associated papillary renal cancer, familial multiple leiomyomatosis and renal cell cancer, SDHx-associated familial pheochromocytoma/ paraganglioma, Birt-Hogg-Dube syndrome, tuberous sclerosis, Cowden syndrome, BAP1- and MITF-associated melanoma-KC predisposition. These syndromes differ in the degree of cancer risk, the quantity, growth and progression rates of associated precancerous lesions, the morphology, and clinical presentations of malignancy itself, and in the response to therapy. Identification of causative germline lesion allows planning the surveillance of a mutation carrier, choosing the right time and extent of surgery, and optimizing treatment regimen. Hereditary KC research often brings forward novel approaches to the management of sporadic “phenocopies” of hereditary syndromes, i.e. sporadic cancers with somatic mutations in similar genes. The main directions for further study of genetic factors of KC are to find novel KC genes, to study risk modifiers in carriers of highly penetrant mutations, to clarify the involvement of hereditary nephropathies in the occurrence of renal cancers.

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