Skip to main content

Advertisement

SpringerLink
Log in

Surveillance for urinary tract cancer in Lynch syndrome

  • Original Article
  • Published:
Familial Cancer Aims and scope Submit manuscript

Abstract

Hereditary non-polyposis colorectal cancer (HNPCC) is an inherited multiorgan cancer syndrome, which when caused by a germline mutation in the mismatch repair (MMR) genes is known as Lynch syndrome (LS). Mutation carriers are at risk for developing cancers primarily in the colon, rectum and endometrium, but also other extra-colonic cancers. Urinary tract cancers (UTC) have in many studies been reported increased in LS and it has been discussed among researchers and clinicians whether or not screening for urological tumours should be included in the surveillance programme and if so what screening procedures are justifiable. The aim of this review was to elucidate the present knowledge from the literature on the risk of UTC in LS and highlight the pros and cons of screening for asymptomatic neoplasia in the urinary tract. The review is based on a systematic literature search in PubMed database followed by a reference list of retrieved articles and manual searches of further relevant articles. In conclusion there is a moderate increased risk of UTC in LS, but a tremendous lack of knowledge on which screening programme, if any at all to establish, and if so what procedures and time intervals are appropriate. It is recommended that all eventually screening for UTC in LS, only should be performed in clinical trials or with a systematic reporting to a HNPCC-register for future evaluation.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

CRC:

Colorectal cancer

IHC:

Immunohistochemistry

HNPCC:

Hereditary non-polyposis colorectal cancer

LS:

Lynch syndrome

MMR:

Mismatch repair genes, MLH1, MSH2, MSH6, PMS1 and PMS2

MSI:

Microsatellite instability

UC:

Urine cytology

US:

Ultrasound

UTC:

Urinary tract cancer

References

  1. Vasen HF, Moslein G, Alonso A, Bernstein I, Bertario L, Blanco I, Burn J, Capella G, Engel C, Frayling I, Friedl W, Hes FJ, Hodgson S, Mecklin JP, Moller P, Nagengast F, Parc Y, Renkonen-Sinisalo L, Sampson JR, Stormorken A, Wijnen J (2007) Guidelines for the clinical management of Lynch syndrome (hereditary non-polyposis cancer). J Med Genet 44:353–362

    Article  PubMed  CAS  Google Scholar 

  2. Vasen HF, Moslein G, Alonso A, Aretz S, Bernstein I, Bertario L, Blanco I, Bulow S, Burn J, Capella G, Colas C, Engel C, Frayling I, Rahner N, Hes FJ, Hodgson S, Mecklin JP, Moller P, Myrhoj T, Nagengast FM, Parc Y, De Ponz LM, Renkonen-Sinisalo L, Sampson JR, Stormorken A, Tejpar S, Thomas HJ, Wijnen J, Lubinski J, Jarvinen H, Claes E, Heinimann K, Karagiannis JA, Lindblom A, Dove-Edwin I, Muller H (2010) Recommendations to improve identification of hereditary and familial colorectal cancer in Europe. Fam Cancer 9:109–115

    Article  PubMed  CAS  Google Scholar 

  3. Vasen HF, Abdirahman M, Brohet R, Langers AM, Kleibeuker JH, KM van, Koornstra JJ, Boot H, Cats A, Dekker E, Sanduleanu S, Poley JW, Hardwick JC, de Vos Tot Nederveen Cappel WH, van der Meulen-de Jong AE, Tan TG, Jacobs MA, Mohamed FL, de Boer SY, van de Meeberg PC, Verhulst ML, Salemans JM, van BN, Westerveld BD, Vecht J, Nagengast FM (2010) One to 2-year surveillance intervals reduce risk of colorectal cancer in families with Lynch syndrome. Gastroenterology 138:2300–2306

    Article  PubMed  Google Scholar 

  4. Stuckless S, Green J, Morgenstern M, Kennedy C, Green R, Woods M, Fitzgerald W, Cox J, Parfrey P (2012) Impact of colonoscopic screening in male and female Lynch syndrome carriers with an MSH2 mutation. Clin Genet 82:439–445

    Article  PubMed  CAS  Google Scholar 

  5. Mecklin JP, Aarnio M, Laara E, Kairaluoma MV, Pylvanainen K, Peltomaki P, Aaltonen LA, Jarvinen HJ (2007) Development of colorectal tumors in colonoscopic surveillance in Lynch syndrome. Gastroenterology 133:1093–1098

    Article  PubMed  Google Scholar 

  6. Engel C, Rahner N, Schulmann K, Holinski-Feder E, Goecke TO, Schackert HK, Kloor M, Steinke V, Vogelsang H, Moslein G, Gorgens H, Dechant S, von Knebel DM, Ruschoff J, Friedrichs N, Buttner R, Loeffler M, Propping P, Schmiegel W (2010) Efficacy of annual colonoscopic surveillance in individuals with hereditary nonpolyposis colorectal cancer. Clin Gastroenterol Hepatol 8:174–182

    Article  PubMed  Google Scholar 

  7. Jarvinen HJ, Aarnio M, Mustonen H, Aktan-Collan K, Aaltonen LA, Peltomaki P, de la Chapelle A, Mecklin JP (2000) Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer. Gastroenterology 118:829–834

    Article  PubMed  CAS  Google Scholar 

  8. Win AK, Young JP, Lindor NM, Tucker KM, Ahnen DJ, Young GP, Buchanan DD, Clendenning M, Giles GG, Winship I, Macrae FA, Goldblatt J, Southey MC, Arnold J, Thibodeau SN, Gunawardena SR, Bapat B, Baron JA, Casey G, Gallinger S, Le ML, Newcomb PA, Haile RW, Hopper JL, Jenkins MA (2012) Colorectal and other cancer risks for carriers and noncarriers from families with a DNA mismatch repair gene mutation: a prospective cohort study. J Clin Oncol 30:958–964

    Article  PubMed  CAS  Google Scholar 

  9. Win AK. Risks of primary extracolonic cancers following colorectal cancer in lynch syndrome. 2012

  10. Watson P, Vasen HF, Mecklin JP, Bernstein I, Aarnio M, Jarvinen HJ, Myrhoj T, Sunde L, Wijnen JT, Lynch HT (2008) The risk of extra-colonic, extra-endometrial cancer in the Lynch syndrome. Int J Cancer 123:444–449

    Article  PubMed  CAS  Google Scholar 

  11. Vasen HF, Stormorken A, Menko FH, Nagengast FM, Kleibeuker JH, Griffioen G, Taal BG, Moller P, Wijnen JT (2001) MSH2 mutation carriers are at higher risk of cancer than MLH1 mutation carriers: a study of hereditary nonpolyposis colorectal cancer families. J Clin Oncol 19:4074–4080

    PubMed  CAS  Google Scholar 

  12. Sijmons RH, Kiemeney LA, Witjes JA, Vasen HF (1998) Urinary tract cancer and hereditary nonpolyposis colorectal cancer: risks and screening options. J Urol 160:466–470

    Article  PubMed  CAS  Google Scholar 

  13. Barrow PJ, Ingham S, O’Hara C, Green K, McIntyre I, Lalloo F, Hill J (2012) Evans DG. The spectrum of urological malignancy in Lynch syndrome, Fam Cancer

    Google Scholar 

  14. Aarnio M, Sankila R, Pukkala E, Salovaara R, Aaltonen LA, de la Chapelle A, Peltomaki P, Mecklin JP, Jarvinen HJ (1999) Cancer risk in mutation carriers of DNA-mismatch-repair genes. Int J Cancer 81:214–218

    Article  PubMed  CAS  Google Scholar 

  15. Aarnio M, Saily M, Juhola M, Gylling A, Peltomaki P, Jarvinen HJ (2012) Mecklin JP. Uroepithelial and kidney carcinoma in Lynch syndrome, Fam Cancer

    Google Scholar 

  16. Aarnio M (2012) Clinicopathological features and management of cancers in lynch syndrome. Patholog Res Int 2012:350309

    PubMed  Google Scholar 

  17. Roupret M, Yates DR, Comperat E, Cussenot O (2008) Upper urinary tract urothelial cell carcinomas and other urological malignancies involved in the hereditary nonpolyposis colorectal cancer (lynch syndrome) tumor spectrum. Eur Urol 54:1226–1236

    Article  PubMed  Google Scholar 

  18. Audenet F, Colin P, Yates DR, Ouzzane A, Pignot G, Long JA, Soulie M, Phe V, Bensadoun H, Guy L, Ruffion A, Valeri A, Cormier L, Droupy S, de La TA, Saint F, Fais PO, Houlgatte A, Cussenot O, Roupret M. A (2012) Proportion of hereditary upper urinary tract urothelial carcinomas are misclassified as sporadic according to a multi-institutional database analysis: proposal of patient-specific risk identification tool. BJU Int

  19. Hartmann A, Zanardo L, Bocker-Edmonston T, Blaszyk H, Dietmaier W, Stoehr R, Cheville JC, Junker K, Wieland W, Knuechel R, Rueschoff J, Hofstaedter F, Fishel R (2002) Frequent microsatellite instability in sporadic tumors of the upper urinary tract. Cancer Res 62:6796–6802

    PubMed  CAS  Google Scholar 

  20. Gylling AH, Nieminen TT, Abdel-Rahman WM, Nuorva K, Juhola M, Joensuu EI, Jarvinen HJ, Mecklin JP, Aarnio M, Peltomaki PT (2008) Differential cancer predisposition in Lynch syndrome: insights from molecular analysis of brain and urinary tract tumors. Carcinogenesis 29:1351–1359

    Article  PubMed  CAS  Google Scholar 

  21. Blaszyk H, Wang L, Dietmaier W, Hofstadter F, Burgart LJ, Cheville JC, Hartmann A (2002) Upper tract urothelial carcinoma: a clinicopathologic study including microsatellite instability analysis. Mod Pathol 15:790–797

    Article  PubMed  Google Scholar 

  22. Bermejo JL, Eng C, Hemminki K (2005) Cancer characteristics in Swedish families fulfilling criteria for hereditary nonpolyposis colorectal cancer. Gastroenterology 129:1889–1899

    Article  PubMed  Google Scholar 

  23. Geary J, Sasieni P, Houlston R, Izatt L, Eeles R, Payne SJ, Fisher S, Hodgson SV (2008) Gene-related cancer spectrum in families with hereditary non-polyposis colorectal cancer (HNPCC). Fam Cancer 7:163–172

    Article  PubMed  CAS  Google Scholar 

  24. van der Post RS, Kiemeney LA, Ligtenberg MJ, Witjes JA, Hulsbergen-van de Kaa CA, Bodmer D, Schaap L, Kets CM, van Krieken JH, Hoogerbrugge N (2010) Risk of urothelial bladder cancer in Lynch syndrome is increased, in particular among MSH2 mutation carriers. J Med Genet 47:464–470

    Article  PubMed  Google Scholar 

  25. Grossman HB, Messing E, Soloway M, Tomera K, Katz G, Berger Y, Shen Y (2005) Detection of bladder cancer using a point-of-care proteomic assay. JAMA 293:810–816

    Article  PubMed  CAS  Google Scholar 

  26. van Rhijn BW, van der Poel HG, van der Kwast TH (2005) Urine markers for bladder cancer surveillance: a systematic review. Eur Urol 47:736–748

    Article  PubMed  Google Scholar 

  27. Jamis-Dow CA, Choyke PL, Jennings SB, Linehan WM, Thakore KN, Walther MM (1996) Small (<or = 3-cm) renal masses: detection with CT versus US and pathologic correlation. Radiology 198:785–788

    PubMed  CAS  Google Scholar 

  28. Acher P, Kiela G, Thomas K, O’Brien T (2010) Towards a rational strategy for the surveillance of patients with Lynch syndrome (hereditary non-polyposis colon cancer) for upper tract transitional cell carcinoma. BJU Int 106:300–302

    Article  PubMed  Google Scholar 

  29. Koornstra JJ, Mourits MJ, Sijmons RH, Leliveld AM, Hollema H, Kleibeuker JH (2009) Management of extra colonic tumours in patients with Lynch syndrome. Lancet Oncol 10:400–408

    Article  PubMed  CAS  Google Scholar 

  30. Lindor NM, Petersen GM, Hadley DW, Kinney AY, Miesfeldt S, Lu KH, Lynch P, Burke W, Press N (2006) Recommendations for the care of individuals with an inherited predisposition to Lynch syndrome: a systematic review. JAMA 296:1507–1517

    Article  PubMed  CAS  Google Scholar 

  31. Zachhau P, Walter S (2012) Urinary tract cancer in patients with hereditary non-polyposis colorectal cancer. Scand J Urol Nephrol 46:5–7

    Article  PubMed  Google Scholar 

  32. Myrhoj T, Andersen MB, Bernstein I (2008) Screening for urinary tract cancer with urine cytology in Lynch syndrome and familial colorectal cancer. Fam Cancer 7:303–307

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Danish HNPCC-register, Department of Gastroenterology and Clinical Research Center, Copenhagen University Hospital, Hvidovre, Denmark

    Inge Thomsen Bernstein & Torben Myrhøj

  2. Department of Surgical Gastroenterology, Aalborg University Hospital, Aalborg, Denmark

    Inge Thomsen Bernstein

Authors
  1. Inge Thomsen Bernstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Torben Myrhøj
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Inge Thomsen Bernstein.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bernstein, I.T., Myrhøj, T. Surveillance for urinary tract cancer in Lynch syndrome. Familial Cancer 12, 279–284 (2013). https://doi.org/10.1007/s10689-013-9634-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10689-013-9634-y

Keywords

Search

Navigation