Lynch syndrome (LS), or hereditary nonpolyposis colorectal cancer, is caused by mutations in mismatch repair (MMR) genes. An increased risk for upper tract urothelial carcinoma (UTUC) has been described in this population; however, data regarding the risk for bladder cancer (BCa) are sparse.
To assess the risk of BCa in MMR mutation carriers and suggest screening and management recommendations.
Design, setting, and participants
Cancer data from 1980 to 2007 were obtained from the Familial Gastrointestinal Cancer Registry in Toronto for 321 persons with known MMR mutations: mutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli) (MLH1); mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli) (MSH2); mutS homolog 6 (E. coli) (MSH6); and PMS2 postmeiotic segregation increased 2 (S. cerevisiae) (PMS2).
Outcome measurements and statistical analysis
Standardized incidence ratios from the Ontario Cancer Registry, using the Surveillance Epidemiology and End Results public database, were used to compare cancer risk in patients with MMR mutations with the Canadian population. Microsatellite instability analysis and immunohistochemistry (IHC) of the MMR proteins were also performed and the results compared with matched sporadic bladder tumors.
Results and limitations
Eleven of 177 patients with MSH2 mutations (6.21%, p
LS patients with MSH2 mutations are at an increased risk for not only UTUC but also BCa and could be offered appropriate screening.
Keywords: Bladder cancer, Lynch syndrome, MSH2, Microsatellite instability, Mismatch repair, Genetic.
a Department of Surgical Oncology, Urology, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada
b Familial Gastrointestinal Cancer Registry, Zane Cohen Center for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada
c Department of Pathology, Mount Sinai Hospital, Toronto, Ontario, Canada
d Department of Surgery, Urology, Mount Sinai Hospital, Toronto, Ontario, Canada
e Department of Urology, Erasmus MC, Rotterdam, The Netherlands
f Department of Urology and Division of Medical Oncology, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY, USA
g Department of Pathology, University Health Network, Toronto, Ontario, Canada
h Department of Pathology, Erasmus MC, Rotterdam, The Netherlands
i Academic Urology Unit and Institute for Cancer Studies, University of Sheffield, Sheffield, United Kingdom
Corresponding author. Department of Surgery, Division of Urology, University of Toronto, Mount Sinai Hospital and University Health Network, 60 Murray St., 6th Floor, Box 19, Toronto, Ontario, M5T 3L9, Canada. Tel. +1 416 586 4800, ext. 3910; Fax: +1 416 586 4776.
© 2012 European Association of Urology, Published by Elsevier B.V.