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Frequent mismatch-repair defects link prostate cancer to Lynch syndrome.
BMC Urol 2016; 16:15BU

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.

Authors+Show Affiliations

Institute of Clinical Sciences, Division of Oncology and Pathology, Lund University, SE-22381, Lund, Sweden.Institute of Clinical Sciences, Division of Oncology and Pathology, Lund University, SE-22381, Lund, Sweden.HNPCC-Register, Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Denmark.Institute of Clinical Sciences, Division of Oncology and Pathology, Lund University, SE-22381, Lund, Sweden.Institute of Clinical Sciences, Division of Oncology and Pathology, Lund University, SE-22381, Lund, Sweden.Institute of Clinical Sciences, Division of Oncology and Pathology, Lund University, SE-22381, Lund, Sweden. mef.nilbert@med.lu.se. HNPCC-Register, Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Denmark. mef.nilbert@med.lu.se.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27013479

Citation

Dominguez-Valentin, Mev, et al. "Frequent Mismatch-repair Defects Link Prostate Cancer to Lynch Syndrome." BMC Urology, vol. 16, 2016, p. 15.
Dominguez-Valentin M, Joost P, Therkildsen C, et al. Frequent mismatch-repair defects link prostate cancer to Lynch syndrome. BMC Urol. 2016;16:15.
Dominguez-Valentin, M., Joost, P., Therkildsen, C., Jonsson, M., Rambech, E., & Nilbert, M. (2016). Frequent mismatch-repair defects link prostate cancer to Lynch syndrome. BMC Urology, 16, p. 15. doi:10.1186/s12894-016-0130-1.
Dominguez-Valentin M, et al. Frequent Mismatch-repair Defects Link Prostate Cancer to Lynch Syndrome. BMC Urol. 2016 Mar 24;16:15. PubMed PMID: 27013479.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Frequent mismatch-repair defects link prostate cancer to Lynch syndrome. AU - Dominguez-Valentin,Mev, AU - Joost,Patrick, AU - Therkildsen,Christina, AU - Jonsson,Mats, AU - Rambech,Eva, AU - Nilbert,Mef, Y1 - 2016/03/24/ PY - 2015/10/21/received PY - 2016/03/16/accepted PY - 2016/3/26/entrez PY - 2016/3/26/pubmed PY - 2016/10/13/medline KW - MLH1 KW - MSH2 KW - MSH6 KW - Microsatellite instability KW - Mismatch repair deficiency SP - 15 EP - 15 JF - BMC urology JO - BMC Urol VL - 16 N2 - 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. SN - 1471-2490 UR - https://www.unboundmedicine.com/medline/citation/27013479/Frequent_mismatch_repair_defects_link_prostate_cancer_to_Lynch_syndrome_ L2 - https://bmcurol.biomedcentral.com/articles/10.1186/s12894-016-0130-1 DB - PRIME DP - Unbound Medicine ER -