Cancer risk in hereditary nonpolyposis colorectal cancer due to MSH6 mutations: impact on counseling and surveillance (2024)

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