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BMC Urology
Published in: BMC Urology 1/2016

Open Access 01-12-2016 | Research article

Frequent mismatch-repair defects link prostate cancer to Lynch syndrome

Authors: Mev Dominguez-Valentin, Patrick Joost, Christina Therkildsen, Mats Jonsson, Eva Rambech, Mef Nilbert

Published in: BMC Urology | Issue 1/2016

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Abstract

Background

A possible role for prostate cancer in Lynch syndrome has been debated based on observations of mismatch-repair defective tumors and reports of an increased risk of prostate cancer in mutation carriers. Potential inclusion of prostate cancer in the Lynch syndrome tumor spectrum is relevant for family classification, risk estimates and surveillance recommendations in mutation carriers.

Methods

We used the population-based Danish HNPCC-register to identify all prostate cancers that developed in mutation carriers and in their first-degree relatives from 288 Lynch syndrome families. The tumors were evaluated for clinicopathologic features and mismatch-repair status, and the cumulative risk of prostate cancer was determined.

Results

In total, 28 prostate cancers developed in 16 mutation carriers and in 12 first-degree relatives at a median age of 63 years. The majority of the tumors were high-grade tumors with Gleason scores 8–10. Prostate cancer was associated with mutations in MSH2, MLH1 and MSH6 with loss of the respective mismatch repair protein in 69 % of the tumors, though a MSI-high phenotype was restricted to 13 % of the tumors. The cumulative risk of prostate cancer at age 70 was 3.7 % (95 % CI: 2.3–4.9).

Conclusion

We provide evidence to link prostate cancer to Lynch syndrome through demonstration of MMR defective tumors and an increased risk of the disease, which suggests that prostate cancer should be considered in the diagnostic work-up of Lynch syndrome.
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Metadata
Title
Frequent mismatch-repair defects link prostate cancer to Lynch syndrome
Authors
Mev Dominguez-Valentin
Patrick Joost
Christina Therkildsen
Mats Jonsson
Eva Rambech
Mef Nilbert
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Urology / Issue 1/2016
Electronic ISSN: 1471-2490
DOI
https://doi.org/10.1186/s12894-016-0130-1

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