Frequent mismatch-repair defects link prostate cancer to Lynch syndrome
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Frequent mismatch-repair defects link prostate cancer to Lynch syndrome. / Dominguez-Valentin, Mev; Joost, Patrick; Therkildsen, Christina; Jonsson, Mats; Rambech, Eva; Nilbert, Mef Christina.
In: BMC Urology, Vol. 16, No. 15, 15, 24.03.2016, p. 1-7.Research output: Contribution to journal › Journal article › Research › peer-review
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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 Christina
PY - 2016/3/24
Y1 - 2016/3/24
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.
AB - 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.
KW - Adaptor Proteins, Signal Transducing
KW - Adenocarcinoma
KW - Aged
KW - Aged, 80 and over
KW - Colorectal Neoplasms, Hereditary Nonpolyposis
KW - DNA Mismatch Repair
KW - DNA-Binding Proteins
KW - Denmark
KW - Germ-Line Mutation
KW - Humans
KW - Immunohistochemistry
KW - Male
KW - Microsatellite Instability
KW - Middle Aged
KW - MutL Protein Homolog 1
KW - MutS Homolog 2 Protein
KW - Mutation
KW - Nuclear Proteins
KW - Prostatic Neoplasms
KW - Registries
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1186/s12894-016-0130-1
DO - 10.1186/s12894-016-0130-1
M3 - Journal article
C2 - 27013479
VL - 16
SP - 1
EP - 7
JO - BMC Urology
JF - BMC Urology
SN - 1471-2490
IS - 15
M1 - 15
ER -
ID: 174211698