Increased risk for urological tumors has been observed in mutation carriers with Lynch syndrome (LS). In this study, we evaluated the clinical features of uroepithelial (bladder and ureter) and kidney cancers in 974 Finnish mutation carriers. Altogether 30 patients had a total of 34 urological tumors: 12 ureter, 12 bladder, and 10 kidney cancers. Urological tumor was the only tumor in 9 (30 %) patients, and metachronous other tumor occurred in 21 (70 %). The occurrence of uroepithelial cancers was significantly higher in MSH2 mutation carriers (6 %; 95 % CI, 2.7–11.0) than in MLH1 carriers (2 %; 95 % CI, 1.1–3.2) and MSH6 mutation carriers (0 %) (p = 0.014). The mean ages of patients at the time of diagnosis were: bladder cancer, 57 years; ureter cancer, 58 years; and kidney cancer, 64 years. Overall 5-year survival rates were 70 % (95 % CI, 0.32–0.89) in bladder cancer, 81 % (95 % CI, 0.45–0.95) in ureter cancer, and 75 % (95 % CI, 0.31–0.93) in kidney cancer. Cancer-specific 5-year survival rates were 70 % (95 % CI, 0.32–0.89) in bladder cancer, 91 % (95 % CI, 0.51–0.98) in ureter cancer, and 100 % in kidney cancer. In conclusion, early age of onset was observed in patients with uroepithelial tumors, but not in patients with kidney cancer. The frequency of uroepithelial tumors was significantly higher in MSH2 mutation carriers than in MLH1 carriers. Further studies with larger numbers of patients, however, are needed to evaluate the potential benefit of surveillance of urological tumors in LS.
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This study was supported by the Academy of Finland, the Sigrid Juselius Foundation, the Finnish Cancer Organizations, Biocentrum Helsinki, the European Research Council (FP7-ERC-232635) and grants from Jyväskylä Central Hospital. We wish to thank Mrs. Tuula Lehtinen and Mrs. Kirsi Pylvänäinen for data collection and general assistance, as well as Mr. Hannu Kautiainen for his assistance with statistics. We also acknowledge Docents Risto Sankila and Eero Pukkala of the Finnish Cancer Registry for their statistical expertise.
Abdel-Rahman WM, Mecklin JP, Peltomaki P (2006) The genetics of HNPCC: application to diagnosis and screening. Crit Rev Oncol Hematol 58:208–220PubMedCrossRefGoogle Scholar
Peltomäki P, Vasen H (2004) Mutations associated with HNPCC predisposition—update of ICG-HNPCC/InSiGHT mutation database. Dis Markers 20:269–276PubMedGoogle Scholar
Holmberg M, Kristo P, Chadwick RB et al. (1998) Mutation sharing, predominant involvement of the MLH1 gene, and description of four novel mutations in hereditary nonpolyposis colorectal cancer. Mutation in brief#144 (Online). Hum Mut 11:482Google Scholar
Lynch HT, Smyrk T (1996) Hereditary nonpolyposis colorectal cancer (Lynch syndrome). An updated review. Cancer 78:1149–1167PubMedCrossRefGoogle Scholar
Watson P, Vasen HFA, Mecklin JP et al (2008) The risk of extracolonic, extra-endometrial cancer in the Lynch syndrome. In J Cancer 123:444–449Google Scholar
Aarnio M, Sankila R, Pukkala E et al (1999) Cancer risk in mutation carriers of DNA-mismatch repair genes. Int J Cancer 81:214–218PubMedCrossRefGoogle Scholar
Vasen HFA, Stormorken A, Menko FM et al (2001) MSH2 mutation carriers are at higher risk of cancer than MLH1 mutation carriers: A study of hereditary nonpolyposis colorectal cancer studies. J Clin Oncol 19:4074–4080PubMedGoogle Scholar
Peltomäki P (2003) Role of DNA mismatch repair genes in the pathogenesis of human cancer. J Clin Oncol 21:1174–1179PubMedCrossRefGoogle Scholar
Gylling AHS, Nieminen TT, Abdel-Rahman WM et al (2008) Differential cancer predisposition in Lynch syndrome: insights from molecular analysis of brain and urinary tumors. Carcinogenesis 29:1351–1359PubMedCrossRefGoogle Scholar
Vasen HFA, Möslein G, Alonso A et al (2007) Guidelines for the clinical management of Lynch syndrome (hereditary non-polyposis cancer). J Med Genet 44:353–362PubMedCrossRefGoogle Scholar
Vasen HF, Wijnen JT, Menko FH et al (1996) Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis. Gastroenterology 110:1020–1027PubMedCrossRefGoogle Scholar
Van der Post RS, Kiemeney LA, Ligtenberg MJL et al (2010) Risk of urothelial bladder cancer in Lynch syndrome is increased, in particular among MSH2 mutation carriers. J Med Genet 47:464–470PubMedCrossRefGoogle Scholar
Finnish Cancer Registry, Helsinki, Finland (2011) The mean ages and relative survival rates (%) of patients in the general population were calculated directly from the original data of the Finnish cancer Registry. www.cancerregistry.fi
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 54:581–592CrossRefGoogle Scholar
Vasen HFA, Mecklin J-P, Khan PM, Lynch HT (1991) The international collaborative group on hereditary nonpolyposis colorectal cancer (ICG-HNPCC). Dis Colon Rectum 34:424–425PubMedCrossRefGoogle Scholar
Vasen HFA, Watson P, Mecklin J-P, Lynch HT (1999) New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the international collaborative group on HNPCC. Gastroenterology 116:1453–1456PubMedCrossRefGoogle Scholar
Sijmons RH, Kiemeney LALM, Witjes JA, Vasen HFA (1998) Urinary tract cancer and hereditary nonpolyposis colorectal cancer: risks and screening options. J Urol 160:466–470PubMedCrossRefGoogle Scholar
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 106(3):300–302CrossRefGoogle Scholar
Grossman HB, Messig E, Soloway M et al (2005) Detection of bladder cancer using a point-of-care proteomic assay. JAMA 293:810–816PubMedCrossRefGoogle Scholar
Koonstra JJ, Mourits MJ, Sijmons RH, Leviveld AM, Hollema H, Kleibeuker JH (2009) Management of extracolonic tumours in patients with Lynch syndrome. Lancet Oncol 10:400–408CrossRefGoogle Scholar