Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/99744
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Type: Journal article
Title: Risk of colorectal cancer for people with a mutation in both a MUTYH and a DNA mismatch repair gene
Author: Win, A.
Reece, J.
Buchanan, D.
Clendenning, M.
Young, J.
Cleary, S.
Kim, H.
Cotterchio, M.
Dowty, J.
MacInnis, R.
Tucker, K.
Winship, I.
Macrae, F.
Burnett, T.
Le Marchand, L.
Casey, G.
Haile, R.
Newcomb, P.
Thibodeau, S.
Lindor, N.
et al.
Citation: Familial Cancer, 2015; 14(4):575-583
Publisher: Springer Netherlands
Issue Date: 2015
ISSN: 1389-9600
1573-7292
Statement of
Responsibility: 
Aung Ko Win, Jeanette C. Reece, Daniel D. Buchanan, Mark Clendenning, Joanne P. Young, Sean P. Cleary, Hyeja Kim, Michelle Cotterchio, James G. Dowty, Robert J. MacInnis, Katherine M. Tucker, Ingrid M. Winship, Finlay A. Macrae, Terrilea Burnett, Loı, c Le Marchand, Graham Casey, Robert W. Haile, Polly A. Newcomb, Stephen N. Thibodeau, Noralane M. Lindor, John L. Hopper, Steven Gallinger, Mark A. Jenkins
Abstract: The base excision repair protein, MUTYH, functionally interacts with the DNA mismatch repair (MMR) system. As genetic testing moves from testing one gene at a time, to gene panel and whole exome next generation sequencing approaches, understandin g the risk associated with co-existence of germline mutations in these genes will be important for clinical interpretation and management. From the Colon Cancer Family Registry, we identified 10 carriers who had both a MUTYH mutation (6 with c.1187G>A p.(Gly396Asp), 3 with c.821G>A p.(Arg274Gln), and 1 with c.536A>G p.(Tyr179Cys)) and a MMR gene mutation (3 in MLH1, 6 in MSH2, and 1 in PMS2), 375 carriers of a single (monoallelic) MUTYH mutation alone, and 469 carriers of a MMR gene mutation alone. Of the 10 carriers of both gene mutations, 8 were diagnosed with colorectal cancer. Using a weighted cohort analysis, we estimated that risk of colorectal cancer for carriers of both a MUTYH and a MMR gene mutation was substantially higher than that for carriers of a MUTYH mutation alone [hazard ratio (HR) 21.5, 95% confidence interval (CI) 9.19-50.1; p < 0.001], but not different from that for carriers of a MMR gene mutation alone (HR 1.94, 95% CI 0.63-5.99; p = 0.25). Within the limited power of this study, there was no evidence that a monoallelic MUTYH gene mutation confers additional risk of colorectal cancer for carriers of a MMR gene mutation alone. Our finding suggests MUTYH mutation testing in MMR gene mutation carriers is not clinically informative.
Keywords: MUTYH; Mismatch repair; Colorectal cancer; Lynch syndrome
Description: Published online: 23 July 2015
Rights: © Springer Science+Business Media Dordrecht 2015
RMID: 0030035003
DOI: 10.1007/s10689-015-9824-x
Appears in Collections:Medicine publications

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