DOI: 10.1200/jco.2001.19.20.4074. <i>MSH2</i> Mutation Carriers Are at Higher Risk of Cancer Than <i>MLH1</i> Mutation Carriers: A Study of Hereditary Nonpolyposis Colorectal Cancer Families

MSH2 Mutation Carriers Are at Higher Risk of Cancer Than MLH1 Mutation Carriers: A Study of Hereditary Nonpolyposis Colorectal Cancer Families

10.1200/jco.2001.19.20.4074

Crossref journal-article

American Society of Clinical Oncology (ASCO)

Journal of Clinical Oncology (233)

Abstract

PURPOSE: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disease characterized by the clustering of colorectal cancer, endometrial cancer, and various other cancers. The disease is caused by mutations in DNA-mismatch-repair (MMR) genes, most frequently in MLH1, MSH2, and MSH6. The aims of the present study were to compare the risk of developing colorectal, endometrial, and other cancers between families with the various MMR-gene mutations. PATIENTS AND METHODS: Clinical and pathologic data were collected from 138 families with HNPCC. Mutation analyses were performed for all families. Survival analysis was used to calculate the cumulative risk of developing cancer in the various subsets of relatives. RESULTS: Mutations were identified in 79 families: 34 in MLH1, 40 in MSH2, and five in MSH6. The lifetime risk of developing cancer at any site was significantly higher for MSH2 mutation carriers than for MLH1 mutation carriers (P < .01). The risk of developing colorectal or endometrial cancer was higher in MSH2 mutation carriers than in MLH1 mutation carriers, but the difference was not significant (P = .13 and P = .057, respectively). MSH2 mutation carriers were found to have a significantly higher risk of developing cancer of the urinary tract (P < .05). The risk of developing cancer of the ovaries, stomach, and brain was also higher in the MSH2 mutation carriers than in the MLH1 mutation carriers, but the difference was not statistically significant. CONCLUSION: Pending large prospective studies, the extension of the current surveillance program in MSH2 mutation carriers with the inclusion of the urinary tract should be considered.

Bibliography

Vasen, H. F. A., Stormorken, A., Menko, F. H., Nagengast, F. M., Kleibeuker, J. H., Griffioen, G., Taal, B. G., Moller, P., & Wijnen, J. T. (2001). MSH2 Mutation Carriers Are at Higher Risk of Cancer Than MLH1 Mutation Carriers: A Study of Hereditary Nonpolyposis Colorectal Cancer Families. Journal of Clinical Oncology, 19(20), 4074â4080.

Authors 9

H. F.A. Vasen (first)
A. Stormorken (additional)
F. H. Menko (additional)
F. M. Nagengast (additional)
J. H. Kleibeuker (additional)
G. Griffioen (additional)
B. G. Taal (additional)
P. Moller (additional)
J. T. Wijnen (additional)

References 20 Referenced 297

10.1097/00001622-199807000-00012
10.1053/gast.1997.v113.pm9322509
10.1053/gast.1996.v110.pm8612988
10.1002/ijc.2910640613
10.1093/hmg/6.1.105
10.1086/513896
10.1038/13773
10.1016/0002-9343(89)90296-9
10.1016/S0016-5085(99)70510-X
10.1056/NEJM199808203390804
10.1002/1097-0142(19930201)71:3<677::AID-CNCR2820710305>3.0.CO;2-#
10.1002/(SICI)1097-0215(19990412)81:2<214::AID-IJC8>3.0.CO;2-L
10.1002/(SICI)1097-0215(19990812)82:4<516::AID-IJC8>3.0.CO;2-U
10.1146/annurev.bi.65.070196.000533
10.1016/0092-8674(95)90319-4
Akiyama Y, Sato H, Yamada T, et al: Germ-line mutation of the hMSH6/GTBP gene in an atypical hereditary nonpolyposis colorectal cancer kindred. Cancer Res 57: 3920,1997-3923,
10.1038/ng1197-271
10.1086/302612
Froggatt NJ, Green J, Brassett C, et al: A common MSH2 mutation in English and North American HNPCC families: Origin, phenotypic expression, and sex-specific differences in colorectal cancer. J Med Genet 36: 97,1999-102,
10.1016/S0022-5347(01)62926-4

Dates

Type	When
Created	8 years, 6 months ago (Feb. 24, 2017, 2:51 a.m.)
Deposited	3 years, 2 months ago (May 25, 2022, 5:46 p.m.)
Indexed	2 weeks, 5 days ago (Aug. 6, 2025, 9:49 a.m.)
Issued	23 years, 10 months ago (Oct. 15, 2001)
Published	23 years, 10 months ago (Oct. 15, 2001)
Published Print	23 years, 10 months ago (Oct. 15, 2001)

Funders 0

None

BibTeX

@article{Vasen_2001, title={MSH2 Mutation Carriers Are at Higher Risk of Cancer Than MLH1 Mutation Carriers: A Study of Hereditary Nonpolyposis Colorectal Cancer Families}, volume={19}, ISSN={1527-7755}, url={http://dx.doi.org/10.1200/jco.2001.19.20.4074}, DOI={10.1200/jco.2001.19.20.4074}, number={20}, journal={Journal of Clinical Oncology}, publisher={American Society of Clinical Oncology (ASCO)}, author={Vasen, H. F.A. and Stormorken, A. and Menko, F. H. and Nagengast, F. M. and Kleibeuker, J. H. and Griffioen, G. and Taal, B. G. and Moller, P. and Wijnen, J. T.}, year={2001}, month=oct, pages={4074–4080} }

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  "abstract": "<jats:p> PURPOSE: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disease characterized by the clustering of colorectal cancer, endometrial cancer, and various other cancers. The disease is caused by mutations in DNA-mismatch-repair (MMR) genes, most frequently in MLH1, MSH2, and MSH6. The aims of the present study were to compare the risk of developing colorectal, endometrial, and other cancers between families with the various MMR-gene mutations. </jats:p><jats:p> PATIENTS AND METHODS: Clinical and pathologic data were collected from 138 families with HNPCC. Mutation analyses were performed for all families. Survival analysis was used to calculate the cumulative risk of developing cancer in the various subsets of relatives. </jats:p><jats:p> RESULTS: Mutations were identified in 79 families: 34 in MLH1, 40 in MSH2, and five in MSH6. The lifetime risk of developing cancer at any site was significantly higher for MSH2 mutation carriers than for MLH1 mutation carriers (P &lt; .01). The risk of developing colorectal or endometrial cancer was higher in MSH2 mutation carriers than in MLH1 mutation carriers, but the difference was not significant (P = .13 and P = .057, respectively). MSH2 mutation carriers were found to have a significantly higher risk of developing cancer of the urinary tract (P &lt; .05). The risk of developing cancer of the ovaries, stomach, and brain was also higher in the MSH2 mutation carriers than in the MLH1 mutation carriers, but the difference was not statistically significant. </jats:p><jats:p> CONCLUSION: Pending large prospective studies, the extension of the current surveillance program in MSH2 mutation carriers with the inclusion of the urinary tract should be considered. </jats:p>",
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