Abstract
BACKGROUND & AIMS: Hereditary nonpolyposis colorectal carcinoma (HNPCC) is caused by a mutated mismatch repair (MMR) gene. The aim of our study was to determine the cumulative risk of developing cancer in a large series of MSH6 mutation carriers. METHODS: Mutation analysis was performed in 20 families with a germline mutation in MSH6. We compared the cancer risks between MSH6 and MLH1/MSH2 mutation carriers. Microsatellite instability (MSI) analysis and immunohistochemistry (IHC) were performed in the available tumors. RESULTS: A total of 146 MSH6 mutation carriers were identified. In these carriers, the cumulative risk for colorectal carcinoma was 69% for men, 30% for women, and 71% for endometrial carcinoma at 70 years of age. The risk for all HNPCC-related tumors was significantly lower in MSH6 than in MLH1 or MSH2 mutation carriers (P = 0.002). In female MSH6 mutation carriers, the risk for colorectal cancer was significantly lower (P = 0.0049) and the risk for endometrial cancer significantly higher (P = 0.02) than in MLH1 and MSH2 mutation carriers. In male carriers, the risk for colorectal cancer was lower in MSH6 mutation carriers, but the difference was not significant (P = 0.0854). MSI analysis in colorectal tumors had a sensitivity of 86% in predicting a MMR defect. IHC in all tumors had a sensitivity of 90% in predicting a mutation in MSH6. CONCLUSIONS: We recommend starting colonoscopic surveillance in female MSH6 mutation carriers from age 30 years. Prophylactic hysterectomy might be considered in carriers older than 50 years. MSI and IHC analysis are sensitive tools to identify families eligible for MSH6 mutation analysis
Original language | English |
---|---|
Pages (from-to) | 17-25 |
Journal | Gastroenterology |
Volume | 127 |
Issue number | 1 |
DOIs | |
Publication status | Published - 2004 |
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Hendriks, Y. M. C., Wagner, A., Morreau, H., Menko, F., Stormorken, A., Quehenberger, F., Sandkuijl, L., Møller, P., Genuardi, M., van Houwelingen, H., Tops, C., van Puijenbroek, M., Verkuijlen, P., Kenter, G., van Mil, A., Meijers-Heijboer, H., Tan, G. B., Breuning, M. H., Fodde, R., ... Vasen, H. (2004). Cancer risk in hereditary nonpolyposis colorectal cancer due to MSH6 mutations: impact on counseling and surveillance. Gastroenterology, 127(1), 17-25. https://doi.org/10.1053/j.gastro.2004.03.068
Hendriks, Yvonne M. C. ; Wagner, Anja ; Morreau, Hans et al. / Cancer risk in hereditary nonpolyposis colorectal cancer due to MSH6 mutations: impact on counseling and surveillance. In: Gastroenterology. 2004 ; Vol. 127, No. 1. pp. 17-25.
@article{d01e0aa1c1ba4c808531d4e23e2c4c93,
title = "Cancer risk in hereditary nonpolyposis colorectal cancer due to MSH6 mutations: impact on counseling and surveillance",
abstract = "BACKGROUND & AIMS: Hereditary nonpolyposis colorectal carcinoma (HNPCC) is caused by a mutated mismatch repair (MMR) gene. The aim of our study was to determine the cumulative risk of developing cancer in a large series of MSH6 mutation carriers. METHODS: Mutation analysis was performed in 20 families with a germline mutation in MSH6. We compared the cancer risks between MSH6 and MLH1/MSH2 mutation carriers. Microsatellite instability (MSI) analysis and immunohistochemistry (IHC) were performed in the available tumors. RESULTS: A total of 146 MSH6 mutation carriers were identified. In these carriers, the cumulative risk for colorectal carcinoma was 69% for men, 30% for women, and 71% for endometrial carcinoma at 70 years of age. The risk for all HNPCC-related tumors was significantly lower in MSH6 than in MLH1 or MSH2 mutation carriers (P = 0.002). In female MSH6 mutation carriers, the risk for colorectal cancer was significantly lower (P = 0.0049) and the risk for endometrial cancer significantly higher (P = 0.02) than in MLH1 and MSH2 mutation carriers. In male carriers, the risk for colorectal cancer was lower in MSH6 mutation carriers, but the difference was not significant (P = 0.0854). MSI analysis in colorectal tumors had a sensitivity of 86% in predicting a MMR defect. IHC in all tumors had a sensitivity of 90% in predicting a mutation in MSH6. CONCLUSIONS: We recommend starting colonoscopic surveillance in female MSH6 mutation carriers from age 30 years. Prophylactic hysterectomy might be considered in carriers older than 50 years. MSI and IHC analysis are sensitive tools to identify families eligible for MSH6 mutation analysis",
author = "Hendriks, {Yvonne M. C.} and Anja Wagner and Hans Morreau and Fred Menko and Astrid Stormorken and Franz Quehenberger and Lodewijk Sandkuijl and Pal M{\o}ller and Maurizio Genuardi and {van Houwelingen}, Hans and Carli Tops and {van Puijenbroek}, Marjo and Paul Verkuijlen and Gemma Kenter and {van Mil}, Anneke and Hanne Meijers-Heijboer and Tan, {Gita B.} and Breuning, {Martijn H.} and Riccardo Fodde and Wijnen, {Juul Th} and Br{\"o}cker-Vriends, {Annette H. J. T.} and Hans Vasen",
year = "2004",
doi = "https://doi.org/10.1053/j.gastro.2004.03.068",
language = "English",
volume = "127",
pages = "17--25",
journal = "Gastroenterology",
issn = "0016-5085",
publisher = "W.B. Saunders Ltd",
number = "1",
}
Hendriks, YMC, Wagner, A, Morreau, H, Menko, F, Stormorken, A, Quehenberger, F, Sandkuijl, L, Møller, P, Genuardi, M, van Houwelingen, H, Tops, C, van Puijenbroek, M, Verkuijlen, P, Kenter, G, van Mil, A, Meijers-Heijboer, H, Tan, GB, Breuning, MH, Fodde, R, Wijnen, JT, Bröcker-Vriends, AHJT & Vasen, H 2004, 'Cancer risk in hereditary nonpolyposis colorectal cancer due to MSH6 mutations: impact on counseling and surveillance', Gastroenterology, vol. 127, no. 1, pp. 17-25. https://doi.org/10.1053/j.gastro.2004.03.068
Cancer risk in hereditary nonpolyposis colorectal cancer due to MSH6 mutations: impact on counseling and surveillance. / Hendriks, Yvonne M. C.; Wagner, Anja; Morreau, Hans et al.
In: Gastroenterology, Vol. 127, No. 1, 2004, p. 17-25.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Cancer risk in hereditary nonpolyposis colorectal cancer due to MSH6 mutations: impact on counseling and surveillance
AU - Hendriks, Yvonne M. C.
AU - Wagner, Anja
AU - Morreau, Hans
AU - Menko, Fred
AU - Stormorken, Astrid
AU - Quehenberger, Franz
AU - Sandkuijl, Lodewijk
AU - Møller, Pal
AU - Genuardi, Maurizio
AU - van Houwelingen, Hans
AU - Tops, Carli
AU - van Puijenbroek, Marjo
AU - Verkuijlen, Paul
AU - Kenter, Gemma
AU - van Mil, Anneke
AU - Meijers-Heijboer, Hanne
AU - Tan, Gita B.
AU - Breuning, Martijn H.
AU - Fodde, Riccardo
AU - Wijnen, Juul Th
AU - Bröcker-Vriends, Annette H. J. T.
AU - Vasen, Hans
PY - 2004
Y1 - 2004
N2 - BACKGROUND & AIMS: Hereditary nonpolyposis colorectal carcinoma (HNPCC) is caused by a mutated mismatch repair (MMR) gene. The aim of our study was to determine the cumulative risk of developing cancer in a large series of MSH6 mutation carriers. METHODS: Mutation analysis was performed in 20 families with a germline mutation in MSH6. We compared the cancer risks between MSH6 and MLH1/MSH2 mutation carriers. Microsatellite instability (MSI) analysis and immunohistochemistry (IHC) were performed in the available tumors. RESULTS: A total of 146 MSH6 mutation carriers were identified. In these carriers, the cumulative risk for colorectal carcinoma was 69% for men, 30% for women, and 71% for endometrial carcinoma at 70 years of age. The risk for all HNPCC-related tumors was significantly lower in MSH6 than in MLH1 or MSH2 mutation carriers (P = 0.002). In female MSH6 mutation carriers, the risk for colorectal cancer was significantly lower (P = 0.0049) and the risk for endometrial cancer significantly higher (P = 0.02) than in MLH1 and MSH2 mutation carriers. In male carriers, the risk for colorectal cancer was lower in MSH6 mutation carriers, but the difference was not significant (P = 0.0854). MSI analysis in colorectal tumors had a sensitivity of 86% in predicting a MMR defect. IHC in all tumors had a sensitivity of 90% in predicting a mutation in MSH6. CONCLUSIONS: We recommend starting colonoscopic surveillance in female MSH6 mutation carriers from age 30 years. Prophylactic hysterectomy might be considered in carriers older than 50 years. MSI and IHC analysis are sensitive tools to identify families eligible for MSH6 mutation analysis
AB - BACKGROUND & AIMS: Hereditary nonpolyposis colorectal carcinoma (HNPCC) is caused by a mutated mismatch repair (MMR) gene. The aim of our study was to determine the cumulative risk of developing cancer in a large series of MSH6 mutation carriers. METHODS: Mutation analysis was performed in 20 families with a germline mutation in MSH6. We compared the cancer risks between MSH6 and MLH1/MSH2 mutation carriers. Microsatellite instability (MSI) analysis and immunohistochemistry (IHC) were performed in the available tumors. RESULTS: A total of 146 MSH6 mutation carriers were identified. In these carriers, the cumulative risk for colorectal carcinoma was 69% for men, 30% for women, and 71% for endometrial carcinoma at 70 years of age. The risk for all HNPCC-related tumors was significantly lower in MSH6 than in MLH1 or MSH2 mutation carriers (P = 0.002). In female MSH6 mutation carriers, the risk for colorectal cancer was significantly lower (P = 0.0049) and the risk for endometrial cancer significantly higher (P = 0.02) than in MLH1 and MSH2 mutation carriers. In male carriers, the risk for colorectal cancer was lower in MSH6 mutation carriers, but the difference was not significant (P = 0.0854). MSI analysis in colorectal tumors had a sensitivity of 86% in predicting a MMR defect. IHC in all tumors had a sensitivity of 90% in predicting a mutation in MSH6. CONCLUSIONS: We recommend starting colonoscopic surveillance in female MSH6 mutation carriers from age 30 years. Prophylactic hysterectomy might be considered in carriers older than 50 years. MSI and IHC analysis are sensitive tools to identify families eligible for MSH6 mutation analysis
U2 - https://doi.org/10.1053/j.gastro.2004.03.068
DO - https://doi.org/10.1053/j.gastro.2004.03.068
M3 - Article
C2 - 15236168
SN - 0016-5085
VL - 127
SP - 17
EP - 25
JO - Gastroenterology
JF - Gastroenterology
IS - 1
ER -
Hendriks YMC, Wagner A, Morreau H, Menko F, Stormorken A, Quehenberger F et al. Cancer risk in hereditary nonpolyposis colorectal cancer due to MSH6 mutations: impact on counseling and surveillance. Gastroenterology. 2004;127(1):17-25. doi: https://doi.org/10.1053/j.gastro.2004.03.068