NDLI: Risk of colorectal cancer for people with a mutation in both a MUTYH and a DNA mismatch repair gene

Content Provider	Springer Nature Link
Author	Win, Aung Ko Reece, Jeanette C. Buchanan, Daniel D. Clendenning, Mark Young, Joanne P. Cleary, Sean P. Kim, Hyeja Cotterchio, Michelle Dowty, James G. MacInnis, Robert J. Tucker, Katherine M. Winship, Ingrid M. Macrae, Finlay A. Burnett, Terrilea Le Marchand, Loïc Casey, Graham Haile, Robert W. Newcomb, Polly A. Thibodeau, Stephen N. Lindor, ralane M. Hopper, John L. Gallinger, Steven Jenkins, Mark A.
Copyright Year	2015
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.
Starting Page	575
Ending Page	583
Page Count	9
File Format	PDF
ISSN	13899600
Journal	Familial Cancer
Volume Number	14
Issue Number	4
e-ISSN	15737292
Language	English
Publisher	Springer Netherlands
Publisher Date	2015-07-23
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	MUTYH Mismatch repair Colorectal cancer Lynch syndrome Cancer Research Human Genetics Epidemiology Biomedicine general
Content Type	Text
Resource Type	Article
Subject	Genetics Cancer Research Genetics (clinical) Oncology

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