Advanced

Frequent mismatch-repair defects link prostate cancer to Lynch syndrome

Dominguez-Valentin, Mev; Joost, Patrick LU ; Therkildsen, Christina LU ; Jönsson, Mats LU ; Rambech, Eva LU and Nilbert, Mef LU (2016) In BMC Urology 16(1). p.15-15
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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
BMC Urology
volume
16
issue
1
pages
15 - 15
publisher
BioMed Central
external identifiers
  • Scopus:84962222394
  • WOS:000372782500002
ISSN
1471-2490
DOI
10.1186/s12894-016-0130-1
language
English
LU publication?
yes
id
bef5528a-cb3b-40a6-a1b9-f96d56bb683b
date added to LUP
2016-04-18 15:13:46
date last changed
2016-10-30 04:46:36
@misc{bef5528a-cb3b-40a6-a1b9-f96d56bb683b,
  abstract     = {<p>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.</p><p>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.</p><p>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).</p><p>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.</p>},
  author       = {Dominguez-Valentin, Mev and Joost, Patrick and Therkildsen, Christina and Jönsson, Mats and Rambech, Eva and Nilbert, Mef},
  issn         = {1471-2490},
  language     = {eng},
  number       = {1},
  pages        = {15--15},
  publisher    = {ARRAY(0x95df7b8)},
  series       = {BMC Urology},
  title        = {Frequent mismatch-repair defects link prostate cancer to Lynch syndrome},
  url          = {http://dx.doi.org/10.1186/s12894-016-0130-1},
  volume       = {16},
  year         = {2016},
}