Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/111199
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Type: Journal article
Title: Risk of extracolonic cancers for people with biallelic and monoallelic mutations in MUTYH
Author: Win, A.
Reece, J.
Dowty, J.
Buchanan, D.
Clendenning, M.
Rosty, C.
Southey, M.
Young, J.
Cleary, S.
Kim, H.
Cotterchio, M.
Macrae, F.
Tucker, K.
Baron, J.
Burnett, T.
Le Marchand, L.
Casey, G.
Haile, R.
Newcomb, P.
Thibodeau, S.
et al.
Citation: International Journal of Cancer, 2016; 139(7):1557-1563
Publisher: Wiley
Issue Date: 2016
ISSN: 0020-7136
1097-0215
Statement of
Responsibility: 
Aung Ko Win, Jeanette C. Reece, James G. Dowty, Daniel D. Buchanan, Mark Clendenning, Christophe Rosty, Melissa C. Southey, Joanne P. Young, Sean P. Cleary, Hyeja Kim, Michelle Cotterchio, Finlay A. Macrae, Katherine M. Tucker, John A. Baron, Terrilea Burnett, Loïc Le Marchand, Graham Casey, Robert W. Haile, Polly A. Newcomb, Stephen N. Thibodeau, John L. Hopper, Steven Gallinger, Ingrid M. Winship, Noralane M. Lindor, and Mark A. Jenkins
Abstract: Germline mutations in the DNA base excision repair gene MUTYH are known to increase a carrier's risk of colorectal cancer. However, the risks of other (extracolonic) cancers for MUTYH mutation carriers are not well defined. We identified 266 probands (91% Caucasians) with a MUTYH mutation (41 biallelic and 225 monoallelic) from the Colon Cancer Family Registry. Mutation status, sex, age and histories of cancer from their 1,903 first- and 3,255 second-degree relatives were analyzed using modified segregation analysis conditioned on the ascertainment criteria. Compared with incidences for the general population, hazard ratios (HRs) (95% confidence intervals [CIs]) for biallelic MUTYH mutation carriers were: urinary bladder cancer 19 (3.7-97) and ovarian cancer 17 (2.4-115). The HRs (95% CI) for monoallelic MUTYH mutation carriers were: gastric cancer 9.3 (6.7-13); hepatobiliary cancer 4.5 (2.7-7.5); endometrial cancer 2.1 (1.1-3.9) and breast cancer 1.4 (1.0-2.0). There was no evidence for an increased risk of cancers at the other sites examined (brain, pancreas, kidney or prostate). Based on the USA population incidences, the estimated cumulative risks (95% CI) to age 70 years for biallelic mutation carriers were: bladder cancer 25% (5-77%) for males and 8% (2-33%) for females and ovarian cancer 14% (2-65%). The cumulative risks (95% CI) for monoallelic mutation carriers were: gastric cancer 5% (4-7%) for males and 2.3% (1.7-3.3%) for females; hepatobiliary cancer 3% (2-5%) for males and 1.4% (0.8-2.3%) for females; endometrial cancer 3% (2%-6%) and breast cancer 11% (8-16%). These unbiased estimates of both relative and absolute risks of extracolonic cancers for people, mostly Caucasians, with MUTYH mutations will be important for their clinical management.
Keywords: MUTYH; cancer risk; penetrance; MUTYH-associated polyposis
Rights: © 2016 UICC
RMID: 0030049729
DOI: 10.1002/ijc.30197
Grant ID: http://purl.org/au-research/grants/nhmrc/1042021
http://purl.org/au-research/grants/nhmrc/1074383
http://purl.org/au-research/grants/nhmrc/1073395
http://purl.org/au-research/grants/nhmrc/1020493
http://purl.org/au-research/grants/nhmrc/1023434
Appears in Collections:Medicine publications

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