International Urology and Nephrology

, Volume 49, Issue 9, pp 1507–1512 | Cite as

Renal cell cancers: unveiling the hereditary ones and saving lives—a tailored diagnostic approach

  • Georgios Kallinikas
  • Helai Habib
  • Dimitrios Tsimiliotis
  • Evangelos Koutsokostas
  • Barna Bokor
Urology - Review


The prevalence of RCC in Europe is 2–3% and increasing every year. Hereditary predisposition is found in 5–8% of all RCC cases. Hereditary syndromes associated with RCC include: Von Hippel–Lindau, hereditary papillary renal cell carcinoma, Birt–Hogg–Dube’, hereditary leiomyomatosis, succinate dehydrogenase’s deficiency, tuberous sclerosis complex and Cowden’s syndrome. These syndromes are related to specific genetic mutations. So far the European Association of Urology and American Urological Association have not established guidelines for referral of patients with RCC for germline mutation screening. The scope of this article is to review which clinical manifestations should direct clinicians’ thinking towards hereditary kidney carcinomas and therefore suggest which patients could benefit from genetic testing.


Genetic testing Renal cell carcinoma Germline mutation Von Hippel–Lindau Kidney neoplasms Genetic counseling 


Compliance with ethical standards

Conflict of interest

All authors declare that there is no involvement in any institute, organization or company regarding financial or nonfinancial relationships that could pose a conflict of interest.

Animals or human participants

This article does not contain any studies with animals or human participants performed by any of the authors.


  1. 1.
    Professionals S-O (2016) Renal cell carcinoma [Internet]. Uroweb.
  2. 2.
    Joaquim AF, Ghizoni E, Tedeschi H, Pereira EB, Giacomini LA (2013) Stereotactic radiosurgery for spinal metastases: a literature review. Einstein São Paulo Braz 11(2):247–255CrossRefGoogle Scholar
  3. 3.
    Motzer RJ, Bander NH, Nanus DM (1996) Renal-cell carcinoma. N Engl J Med 335(12):865–875CrossRefPubMedGoogle Scholar
  4. 4.
    Motzer RJ, Russo P, Nanus DM, Berg WJ (1997) Renal cell carcinoma. Curr Probl Cancer 21(4):185–232CrossRefPubMedGoogle Scholar
  5. 5.
    Cohen HT, McGovern FJ (2005) Renal-cell carcinoma. N Engl J Med 353(23):2477–2490CrossRefPubMedGoogle Scholar
  6. 6.
    Linehan WM, Srinivasan R, Schmidt LS (2010) The genetic basis of kidney cancer: a metabolic disease. Nat Rev Urol 7(5):277–285CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Gudbjartsson T, Jónasdóttir TJ, Thoroddsen A et al (2002) A population-based familial aggregation analysis indicates genetic contribution in a majority of renal cell carcinomas. Int J Cancer 100(4):476–479CrossRefPubMedGoogle Scholar
  8. 8.
    Riley BD, Culver JO, Skrzynia C et al (2012) Essential elements of genetic cancer risk assessment, counseling, and testing: updated recommendations of the National Society of Genetic Counselors. J Genet Couns 21(2):151–161CrossRefPubMedGoogle Scholar
  9. 9.
    Robson ME, Bradbury AR, Arun B et al (2015) American Society of Clinical Oncology Policy Statement Update: genetic and genomic testing for cancer susceptibility. J Clin Oncol Off J Am Soc Clin Oncol 33(31):3660–3667CrossRefGoogle Scholar
  10. 10.
    Axwijk PH, Kluijt I, de Jong D, Gille H, Teertstra J, Horenblas S (2010) Hereditary causes of kidney tumours. Eur J Clin Invest 40(5):433–439CrossRefPubMedGoogle Scholar
  11. 11.
    Zbar B, Glenn G, Merino M et al (2007) Familial renal carcinoma: clinical evaluation, clinical subtypes and risk of renal carcinoma development. J Urol 177(2):461–465 (discussion 465) CrossRefPubMedGoogle Scholar
  12. 12.
    Morrison PJ, Donnelly DE, Atkinson AB, Maxwell AP (2010) Advances in the genetics of familial renal cancer. Oncologist 15(6):532–538CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Lindor NM, McMaster ML, Lindor CJ, Greene MH, National Cancer Institute, Division of Cancer Prevention, Community Oncology and Prevention Trials Research Group (2008) Concise handbook of familial cancer susceptibility syndromes—second edition. J Natl Cancer Inst Monogr 38(1):1–93Google Scholar
  14. 14.
    Orphanet: Birt Hogg Dubé syndrome (2016) [Internet].
  15. 15.
    Yang P, Cornejo KM, Sadow PM et al (2014) Renal cell carcinoma in tuberous sclerosis complex. Am J Surg Pathol 38(7):895–909CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Banumathy G, Cairns P (2010) Signaling pathways in renal cell carcinoma. Cancer Biol Ther 10(7):658–664CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Gad S, Lefèvre SH, Khoo SK et al (2007) Mutations in BHD and TP53 genes, but not in HNF1beta gene, in a large series of sporadic chromophobe renal cell carcinoma. Br J Cancer 96(2):336–340CrossRefPubMedGoogle Scholar
  18. 18.
    Schmidt L, Junker K, Nakaigawa N et al (1999) Novel mutations of the MET proto-oncogene in papillary renal carcinomas. Oncogene 18(14):2343–2350CrossRefPubMedGoogle Scholar
  19. 19.
    Violette PD, Kamel-Reid S, Graham GE et al (2014) Knowledge of genetic testing for hereditary kidney cancer in Canada is lacking: the results of the Canadian national hereditary kidney cancer needs assessment survey. Can Urol Assoc J 8(11–12):E832–E840CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Wallen EM, Pruthi RS, Joyce GF, Wise M, Urologic Diseases in America Project (2007) Kidney cancer. J Urol 177(6):2006–2019CrossRefPubMedGoogle Scholar
  21. 21.
    Trepanier A, Ahrens M, McKinnon W et al (2004) Genetic cancer risk assessment and counseling: recommendations of the national society of genetic counselors. J Genet Couns 13(2):83–114CrossRefPubMedGoogle Scholar
  22. 22.
    Purdue MP, Johansson M, Zelenika D et al (2011) Genome-wide association study of renal cell carcinoma identifies two susceptibility loci on 2p21 and 11q13.3. Nat Genet 43(1):60–65CrossRefPubMedGoogle Scholar
  23. 23.
    Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61(2):69–90CrossRefPubMedGoogle Scholar
  24. 24.
    Shuch B, Vourganti S, Ricketts CJ et al (2014) Defining early-onset kidney cancer: implications for germline and somatic mutation testing and clinical management. J Clin Oncol 32(5):431–437CrossRefPubMedGoogle Scholar
  25. 25.
    Schmidt LS, Nickerson ML, Angeloni D et al (2004) Early onset hereditary papillary renal carcinoma: germline missense mutations in the tyrosine kinase domain of the met proto-oncogene. J Urol 172(4 Pt 1):1256–1261CrossRefPubMedGoogle Scholar
  26. 26.
    Gläsker S, Neumann HP, Koch CA, Vortmeyer AO (2016) Von Hippel-Lindau Disease [Internet]. In: De Groot LJ, Beck-Peccoz P, Chrousos G, et al (eds). Endotext., Inc., South Dartmouth.
  27. 27.
    Grubb RL, Franks ME, Toro J et al (2007) Hereditary leiomyomatosis and renal cell cancer: a syndrome associated with an aggressive form of inherited renal cancer. J Urol 177(6):2074–2080CrossRefPubMedGoogle Scholar
  28. 28.
    Pavlovich CP, Grubb RL, Hurley K et al (2005) Evaluation and management of renal tumors in the Birt–Hogg–Dubé syndrome. J Urol 173(5):1482–1486CrossRefPubMedGoogle Scholar
  29. 29.
    Walther MM, Choyke PL, Weiss G et al (1995) Parenchymal sparing surgery in patients with hereditary renal cell carcinoma. J Urol 153(3 Pt 2):913–916PubMedGoogle Scholar
  30. 30.
    Lubensky IA, Schmidt L, Zhuang Z et al (1999) Hereditary and sporadic papillary renal carcinomas with c-met mutations share a distinct morphological phenotype. Am J Pathol 155(2):517–526CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Schmidt LS, Warren MB, Nickerson ML et al (2001) Birt–Hogg–Dubé syndrome, a genodermatosis associated with spontaneous pneumothorax and kidney neoplasia, maps to chromosome 17p11.2. Am J Hum Genet 69(4):876–882CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Duffey BG, Choyke PL, Glenn G et al (2004) The relationship between renal tumor size and metastases in patients with von Hippel–Lindau disease. J Urol 172(1):63–65CrossRefPubMedGoogle Scholar
  33. 33.
    Wei M-H, Toure O, Glenn GM et al (2006) Novel mutations in FH and expansion of the spectrum of phenotypes expressed in families with hereditary leiomyomatosis and renal cell cancer. J Med Genet 43(1):18–27CrossRefPubMedGoogle Scholar
  34. 34.
    Reaume MN, Graham GE, Tomiak E et al (2013) Canadian guideline on genetic screening for hereditary renal cell cancers. Can Urol Assoc J 7(9–10):319–323CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Miller FA, Krueger P, Christensen RJ, Ahern C, Carter RF, Kamel-Reid S (2009) Postal survey of physicians and laboratories: practices and perceptions of molecular oncology testing. BMC Health Serv Res 9:131CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Silversides A (2007) The wide gap between genetic research and clinical needs. CMAJ Can Med Assoc J 176(3):315–316CrossRefGoogle Scholar
  37. 37.
    Weldon CB, Trosman JR, Gradishar WJ, Benson AB, Schink JC (2012) Barriers to the use of personalized medicine in breast cancer. J Oncol Pract Am Soc Clin Oncol 8(4):e24–e31CrossRefGoogle Scholar
  38. 38.
    Crino PB, Nathanson KL, Henske EP (2006) The tuberous sclerosis complex. N Engl J Med 355(13):1345–1356CrossRefPubMedGoogle Scholar
  39. 39.
    American Society of Clinical Oncology (2003) American Society of Clinical Oncology policy statement update: genetic testing for cancer susceptibility. J Clin Oncol Off J Am Soc Clin Oncol 21(12):2397–2406CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2017

Authors and Affiliations

  • Georgios Kallinikas
    • 1
  • Helai Habib
    • 2
  • Dimitrios Tsimiliotis
    • 3
  • Evangelos Koutsokostas
    • 4
  • Barna Bokor
    • 1
  1. 1.Department of UrologyKent and Canterbury HospitalCanterburyUK
  2. 2.Department of Upper G I SurgeryUCLHLondonUK
  3. 3.Department of UrologyGeneral Hospital of ChalkidaChalkidaGreece
  4. 4.Department of UrologyKonstantopouleion-Patision HospitalNea IoniaGreece

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