Skip to main content
SpringerLink
Log in
SpringerLink
Log in

Hereditary Kidney Cancer Syndromes

  • Chapter
Kidney Cancer

  • 1055 Accesses

Abstract

In 2014, there are over 65,000 newly diagnosed cases of kidney cancer, responsible for nearly 14,000 deaths. While the death rates fell by 0.9 % per year from 2006 to 2010, it is still very much a lethal disease. Current expert opinion suggests that while the overwhelming majority of RCC is sporadic in nature, hereditary kidney cancer accounts for 5–8 % of cases. This number may be a gross estimation and with the explosion of next-generation sequencing techniques. More syndromes are expected to be discovered, some with highly complex inheritance patterns.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. American Cancer Society (2014) Cancer facts and figures 2014. American Cancer Society, Atlanta

    Google Scholar 

  2. Linehan WM et al (2009) Hereditary kidney cancer: unique opportunity for disease-based therapy. Cancer 115(10 Suppl):2252–2261

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Liu H, Sundquist J, Hemminki K (2011) Familial renal cell carcinoma from the Swedish Family-Cancer Database. Eur Urol 60(5):987–993

    Article  PubMed  Google Scholar 

  4. Shuch B et al (2014) Defining early-onset kidney cancer: implications for germline and somatic mutation testing and clinical management. J Clin Oncol 32(5):431–437

    Article  PubMed Central  PubMed  Google Scholar 

  5. Linehan WM, Ricketts CJ (2013) The metabolic basis of kidney cancer. Semin Cancer Biol 23(1):46–55

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Reaume MN et al (2013) Canadian guideline on genetic screening for hereditary renal cell cancers. Can Urol Assoc J 7(9–10):319–323

    PubMed Central  PubMed  Google Scholar 

  7. Nickerson ML et al (2008) Improved identification of von Hippel-Lindau gene alterations in clear cell renal tumors. Clin Cancer Res 14(15):4726–4734

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Tory K et al (1989) Specific genetic change in tumors associated with von Hippel-Lindau disease. J Natl Cancer Inst 81(14):1097–1101

    Article  CAS  PubMed  Google Scholar 

  9. Hosoe S et al (1990) Localization of the von Hippel-Lindau disease gene to a small region of chromosome 3. Genomics 8(4):634–640

    Article  CAS  PubMed  Google Scholar 

  10. Latif F et al (1993) Identification of the von Hippel-Lindau disease tumor suppressor gene. Science 260(5112):1317–1320

    Article  CAS  PubMed  Google Scholar 

  11. Lonser RR et al (2003) von Hippel-Lindau disease. Lancet 361(9374):2059–2067

    Article  CAS  PubMed  Google Scholar 

  12. Poston CD et al (1995) Characterization of the renal pathology of a familial form of renal cell carcinoma associated with von Hippel-Lindau disease: clinical and molecular genetic implications. J Urol 153(1):22–26

    Article  CAS  PubMed  Google Scholar 

  13. Neumann HP et al (1998) Prevalence, morphology and biology of renal cell carcinoma in von Hippel-Lindau disease compared to sporadic renal cell carcinoma. J Urol 160(4):1248–1254

    Article  CAS  PubMed  Google Scholar 

  14. Chen F et al (1995) Germline mutations in the von Hippel-Lindau disease tumor suppressor gene: correlations with phenotype. Hum Mutat 5(1):66–75

    Article  CAS  PubMed  Google Scholar 

  15. McNeill A et al (2009) Genotype-phenotype correlations in VHL exon deletions. Am J Med Genet A 149A(10):2147–2151

    Article  CAS  PubMed  Google Scholar 

  16. Zbar B et al (1994) Hereditary papillary renal cell carcinoma. J Urol 151(3):561–566

    CAS  PubMed  Google Scholar 

  17. Zbar B et al (1995) Hereditary papillary renal cell carcinoma: clinical studies in 10 families. J Urol 153(3 Pt 2):907–912

    CAS  PubMed  Google Scholar 

  18. Schmidt L et al (1997) Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas. Nat Genet 16(1):68–73

    Article  CAS  PubMed  Google Scholar 

  19. Bottaro DP et al (1991) Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product. Science 251(4995):802–804

    Article  CAS  PubMed  Google Scholar 

  20. Zhuang Z et al (1998) Trisomy 7-harbouring non-random duplication of the mutant MEt allele in hereditary papillary renal carcinomas. Nat Genet 20(1):66–69

    Google Scholar 

  21. Schmidt L et al (1999) Novel mutations of the MET proto-oncogene in papillary renal carcinomas. Oncogene 18(14):2343–2350

    Article  CAS  PubMed  Google Scholar 

  22. Schmidt L et al (1998) Two North American families with hereditary papillary renal carcinoma and identical novel mutations in the MET proto-oncogene. Cancer Res 58(8):1719–1722

    CAS  PubMed  Google Scholar 

  23. Schmidt LS 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):1256–1261

    Article  PubMed  Google Scholar 

  24. Lubensky IA et al (1999) Hereditary and sporadic papillary renal carcinomas with c-met mutations share a distinct morphological phenotype. Am J Pathol 155(2):517–526

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Ornstein DK et al (2000) Prevalence of microscopic tumors in normal appearing renal parenchyma of patients with hereditary papillary renal cancer. J Urol 163(2):431–433

    Article  CAS  PubMed  Google Scholar 

  26. Kloepfer HW et al (1958) Hereditary multiple leiomyoma of the skin. Am J Hum Genet 10(1):48–52

    CAS  PubMed Central  PubMed  Google Scholar 

  27. Launonen V et al (2001) Inherited susceptibility to uterine leiomyomas and renal cell cancer. Proc Natl Acad Sci U S A 98(6):3387–3392

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Merino MJ et al (2007) The morphologic spectrum of kidney tumors in hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome. Am J Surg Pathol 31(10):1578–1585

    Article  PubMed  Google Scholar 

  29. Reed WB, Walker R, Horowitz R (1973) Cutaneous leiomyomata with uterine leiomyomata. Acta Derm Venereol 53(5):409–416

    CAS  PubMed  Google Scholar 

  30. Alam NA et al (2001) Localization of a gene (MCUL1) for multiple cutaneous leiomyomata and uterine fibroids to chromosome 1q42.3-q43. Am J Hum Genet 68(5):1264–1269

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Tomlinson IP et al (2002) Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer. Nat Genet 30(4):406–410

    Article  CAS  PubMed  Google Scholar 

  32. Isaacs JS et al (2005) HIF overexpression correlates with biallelic loss of fumarate hydratase in renal cancer: novel role of fumarate in regulation of HIF stability. Cancer Cell 8(2):143–153

    Article  CAS  PubMed  Google Scholar 

  33. Vanharanta S et al (2006) Distinct expression profile in fumarate-hydratase-deficient uterine fibroids. Hum Mol Genet 15(1):97–103

    Article  CAS  PubMed  Google Scholar 

  34. Grubb RL 3rd et al (2007) Hereditary leiomyomatosis and renal cell cancer: a syndrome associated with an aggressive form of inherited renal cancer. J Urol 177(6):2074–2079; discussion 2079–2080

    Article  CAS  PubMed  Google Scholar 

  35. Menko FH et al (2014) Hereditary leiomyomatosis and renal cell cancer (HLRCC): renal cancer risk, surveillance and treatment. Fam Cancer 13:637–644

    Article  CAS  PubMed  Google Scholar 

  36. Shuch B et al (2013) Adrenal nodular hyperplasia in hereditary leiomyomatosis and renal cell cancer. J Urol 189(2):430–435

    Article  PubMed Central  PubMed  Google Scholar 

  37. Srigley JR et al (2013) The International Society of Urological Pathology (ISUP) Vancouver classification of renal neoplasia. Am J Surg Pathol 37(10):1469–1489

    Article  PubMed  Google Scholar 

  38. Birt AR, Hogg GR, Dube WJ (1977) Hereditary multiple fibrofolliculomas with trichodiscomas and acrochordons. Arch Dermatol 113(12):1674–1677

    Article  CAS  PubMed  Google Scholar 

  39. Schmidt LS et al (2001) Birt-Hogg-Dube syndrome, a genodermatosis associated with spontaneous pneumothorax and kidney neoplasia, maps to chromosome 17p11.2. Am J Hum Genet 69(4):876–882

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Baba M et al (2006) Folliculin encoded by the BHD gene interacts with a binding protein, FNIP1, and AMPK, and is involved in AMPK and mTOR signaling. Proc Natl Acad Sci U S A 103(42):15552–15557

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Nickerson ML et al (2002) Mutations in a novel gene lead to kidney tumors, lung wall defects, and benign tumors of the hair follicle in patients with the Birt-Hogg-Dube syndrome. Cancer Cell 2(2):157–164

    Article  CAS  PubMed  Google Scholar 

  42. Hasumi Y et al (2009) Homozygous loss of BHD causes early embryonic lethality and kidney tumor development with activation of mTORC1 and mTORC2. Proc Natl Acad Sci U S A 106(44):18722–18727

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Zbar B et al (2002) Risk of renal and colonic neoplasms and spontaneous pneumothorax in the Birt-Hogg-Dube syndrome. Cancer Epidemiol Biomarkers Prev 11(4):393–400

    PubMed  Google Scholar 

  44. Roth JS et al (1993) Bilateral renal cell carcinoma in the Birt-Hogg-Dube syndrome. J Am Acad Dermatol 29(6):1055–1056

    Article  CAS  PubMed  Google Scholar 

  45. Schmidt LS et al (2005) Germline BHD-mutation spectrum and phenotype analysis of a large cohort of families with Birt-Hogg-Dube syndrome. Am J Hum Genet 76(6):1023–1033

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  46. Toro JR et al (1999) Birt-Hogg-Dube syndrome: a novel marker of kidney neoplasia. Arch Dermatol 135(10):1195–1202

    Article  CAS  PubMed  Google Scholar 

  47. Pavlovich CP et al (2002) Renal tumors in the Birt-Hogg-Dube syndrome. Am J Surg Pathol 26(12):1542–1552

    Article  PubMed  Google Scholar 

  48. Pavlovich CP et al (2005) Evaluation and management of renal tumors in the Birt-Hogg-Dube syndrome. J Urol 173(5):1482–1486

    Article  PubMed  Google Scholar 

  49. Shuch B et al (2014) The genetic basis of pheochromocytoma and paraganglioma: implications for management. Urology 83(6):1225–1232

    Article  PubMed  Google Scholar 

  50. Selak MA et al (2005) Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase. Cancer Cell 7(1):77–85

    Article  CAS  PubMed  Google Scholar 

  51. Neumann HP et al (2004) Distinct clinical features of paraganglioma syndromes associated with SDHB and SDHD gene mutations. JAMA 292(8):943–951

    Article  CAS  PubMed  Google Scholar 

  52. Ricketts C et al (2008) Germline SDHB mutations and familial renal cell carcinoma. J Natl Cancer Inst 100(17):1260–1262

    Article  CAS  PubMed  Google Scholar 

  53. Janeway KA et al (2011) Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking KIT and PDGFRA mutations. Proc Natl Acad Sci U S A 108(1):314–318

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  54. European Chromosome 16 Tuberous Sclerosis Consortium (1993) Identification and characterization of the tuberous sclerosis gene on chromosome 16. Cell 75(7):1305–1315

    Article  Google Scholar 

  55. van Slegtenhorst M et al (1997) Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34. Science 277(5327):805–808

    Article  PubMed  Google Scholar 

  56. Kenerson HL et al (2002) Activated mammalian target of rapamycin pathway in the pathogenesis of tuberous sclerosis complex renal tumors. Cancer Res 62(20):5645–5650

    CAS  PubMed  Google Scholar 

  57. Liu MY, Poellinger L, Walker CL (2003) Up-regulation of hypoxia-inducible factor 2alpha in renal cell carcinoma associated with loss of Tsc-2 tumor suppressor gene. Cancer Res 63(10):2675–2680

    CAS  PubMed  Google Scholar 

  58. Crino PB, Nathanson KL, Henske EP (2006) The tuberous sclerosis complex. N Engl J Med 355(13):1345–1356

    Article  CAS  PubMed  Google Scholar 

  59. Bjornsson J et al (1996) Tuberous sclerosis-associated renal cell carcinoma. Clinical, pathological, and genetic features. Am J Pathol 149(4):1201–1208

    CAS  PubMed Central  PubMed  Google Scholar 

  60. Nelen MR et al (1999) Novel PTEN mutations in patients with Cowden disease: absence of clear genotype-phenotype correlations. Eur J Hum Genet 7(3):267–273

    Article  CAS  PubMed  Google Scholar 

  61. Liaw D et al (1997) Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. Nat Genet 16(1):64–67

    Article  CAS  PubMed  Google Scholar 

  62. Nelen MR et al (1996) Localization of the gene for Cowden disease to chromosome 10q22-23. Nat Genet 13(1):114–116

    Article  CAS  PubMed  Google Scholar 

  63. Headington JT, French AJ (1962) Primary neoplasms of the hair follicle. Histogenesis and classification. Arch Dermatol 86:430–441

    Article  CAS  PubMed  Google Scholar 

  64. Tan MH et al (2012) Lifetime cancer risks in individuals with germline PTEN mutations. Clin Cancer Res 18(2):400–407

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  65. Shuch B et al (2013) Germline PTEN mutation Cowden syndrome: an underappreciated form of hereditary kidney cancer. J Urol 190(6):1990–1998

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  66. Woodward ER et al (2010) Population-based survey of cancer risks in chromosome 3 translocation carriers. Genes Chromosomes Cancer 49(1):52–58

    Article  CAS  PubMed  Google Scholar 

  67. Kanayama H et al (2001) Association of a novel constitutional translocation t(1q;3q) with familial renal cell carcinoma. J Med Genet 38(3):165–170

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  68. Schmidt L et al (1995) Mechanism of tumorigenesis of renal carcinomas associated with the constitutional chromosome 3;8 translocation. Cancer J Sci Am 1(3):191–195

    CAS  PubMed  Google Scholar 

  69. Alanen KA et al (1984) Renal oncocytoma: the incidence of 18 surgical and 12 autopsy cases. Histopathology 8(5):731–737

    Article  CAS  PubMed  Google Scholar 

  70. Dechet CB et al (1999) Renal oncocytoma: multifocality, bilateralism, metachronous tumor development and coexistent renal cell carcinoma. J Urol 162(1):40–42

    Article  CAS  PubMed  Google Scholar 

  71. Perez-Ordonez B et al (1997) Renal oncocytoma: a clinicopathologic study of 70 cases. Am J Surg Pathol 21(8):871–883

    Article  CAS  PubMed  Google Scholar 

  72. Weirich G et al (1998) Familial renal oncocytoma: clinicopathological study of 5 families. J Urol 160(2):335–340

    Article  CAS  PubMed  Google Scholar 

  73. Tickoo SK et al (1999) Renal oncocytosis: a morphologic study of fourteen cases. Am J Surg Pathol 23(9):1094–1101

    Article  CAS  PubMed  Google Scholar 

  74. Clark JE (1970) Transplantation for bilateral renal tumors. JAMA 211(8):1379

    Article  CAS  PubMed  Google Scholar 

  75. Jochimsen PR, Braunstein PM, Najarian JS (1969) Renal allotransplantation for bilateral renal tumors. JAMA 210(9):1721–1724

    Article  CAS  PubMed  Google Scholar 

  76. Bratslavsky G, Linehan WM (2010) Long-term management of bilateral, multifocal, recurrent renal carcinoma. Nat Rev Urol 7(5):267–275

    Article  PubMed Central  PubMed  Google Scholar 

  77. Carini M et al (2006) Simple enucleation for the treatment of PT1a renal cell carcinoma: our 20-year experience. Eur Urol 50(6):1263–1268; discussion 1269–1271

    Article  PubMed  Google Scholar 

  78. Goldfarb DA et al (1997) Results of renal transplantation in patients with renal cell carcinoma and von Hippel-Lindau disease. Transplantation 64(12):1726–1729

    Article  CAS  PubMed  Google Scholar 

  79. Herring JC et al (2001) Parenchymal sparing surgery in patients with hereditary renal cell carcinoma: 10-year experience. J Urol 165(3):777–781

    Article  CAS  PubMed  Google Scholar 

  80. Ricketts CJ et al (2012) Succinate dehydrogenase kidney cancer: an aggressive example of the Warburg effect in cancer. J Urol 188(6):2063–2071

    Article  CAS  PubMed  Google Scholar 

  81. Shuch B et al (2014) Adverse health outcomes associated with surgical management of the small renal mass. J Urol 191(2):301–309

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Urology, Yale School of Medicine, New Haven, CT, USA

    Shu Pan MD

  2. Department of Urology and Diagnostic Radiology, Yale School of Medicine, New Haven, CT, USA

    Brian Shuch MD

Authors
  1. Shu Pan MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Brian Shuch MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Brian Shuch MD .

Editor information

Editors and Affiliations

  1. Department of Internal Medicine, Division of Hematology - Oncology, University of California Davis, School of Medicine UC Davis Comprehensive Cancer center, Sacramento, California, USA

    Primo N. Lara

  2. Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA

    Eric Jonasch

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing

About this chapter

Cite this chapter

Pan, S., Shuch, B. (2015). Hereditary Kidney Cancer Syndromes. In: Lara, P., Jonasch, E. (eds) Kidney Cancer. Springer, Cham. https://doi.org/10.1007/978-3-319-17903-2_8

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-17903-2_8

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-17902-5

  • Online ISBN: 978-3-319-17903-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation