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PMID: 24444654 Published · ppublish English Journal Article Multicenter Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Risk of colorectal cancer for carriers of mutations in MUTYH, with and without a family history of cancer.

Gastroenterology ·Vol. 146 ·No. 5 ·2014-05-00 ·Pages 1208-11.e1-5

Win AK, Dowty JG, Cleary SP, Kim H, Buchanan DD, Young JP, Clendenning M, Rosty C, MacInnis RJ, Giles GG, Boussioutas A, Macrae FA, Parry S, Goldblatt J, Baron JA, Burnett T, Le Marchand L, Newcomb PA, Haile RW, Hopper JL, Cotterchio M, Gallinger S, Lindor NM, Tucker KM, Winship IM, Jenkins MA

Abstract

We studied 2332 individuals with monoallelic mutations in MUTYH among 9504 relatives of 264 colorectal cancer (CRC) cases with a MUTYH mutation. We estimated CRC risks through 70 years of age of 7.2% for male carriers of monoallelic mutations (95% confidence interval [CI], 4.6%-11.3%) and 5.6% for female carriers of monoallelic mutations (95% CI, 3.6%-8.8%), irrespective of family history. For monoallelic MUTYH mutation carriers with a first-degree relative with CRC diagnosed by 50 years of age who does not have the MUTYH mutation, risks of CRC were 12.5% for men (95% CI, 8.6%-17.7%) and 10% for women (95% CI, 6.7%-14.4%). Risks of CRC for carriers of monoallelic mutations in MUTYH with a first-degree relative with CRC are sufficiently high to warrant more intensive screening than for the general population.

Keywords
Base Excision Repair Gene Colon Cancer DNA Damage Response Genetics
MeSH Terms
Adult Aged Aged, 80 and over Australia Colorectal Neoplasms/genetics DNA Glycosylases/genetics Female Genetic Predisposition to Disease Heredity Heterozygote Humans Male Middle Aged Mutation New Zealand North America Pedigree Phenotype Registries Risk Assessment Risk Factors
Chemicals
DNA Glycosylases mutY adenine glycosylase
Authors & Affiliations
26 authors, click to expand affiliations / ORCID
Win Aung Ko
Centre for Epidemiology and Biostatistics, The University of Melbourne, Parkville, Victoria, Australia.
Dowty James G
Centre for Epidemiology and Biostatistics, The University of Melbourne, Parkville, Victoria, Australia.
Cleary Sean P
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada; Cancer Care Ontario, Toronto, Ontario, Canada.
Kim Hyeja
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada; Cancer Care Ontario, Toronto, Ontario, Canada.
Buchanan Daniel D
Cancer and Population Studies Group, Queensland Institute of Medical Research, Bancroft Centre, Herston, Queensland, Australia.
Young Joanne P
Cancer and Population Studies Group, Queensland Institute of Medical Research, Bancroft Centre, Herston, Queensland, Australia.
Clendenning Mark
Cancer and Population Studies Group, Queensland Institute of Medical Research, Bancroft Centre, Herston, Queensland, Australia.
Rosty Christophe
Cancer and Population Studies Group, Queensland Institute of Medical Research, Bancroft Centre, Herston, Queensland, Australia; Department of Molecular and Cellular Pathology, University of Queensland, Herston, Queensland, Australia; Envoi Specialist Pathologists, Herston, Queensland, Australia.
MacInnis Robert J
Centre for Epidemiology and Biostatistics, The University of Melbourne, Parkville, Victoria, Australia; Cancer Epidemiology Centre, Cancer Council Victoria, Carlton, Victoria, Australia.
Giles Graham G
Centre for Epidemiology and Biostatistics, The University of Melbourne, Parkville, Victoria, Australia; Cancer Epidemiology Centre, Cancer Council Victoria, Carlton, Victoria, Australia.
Boussioutas Alex
Department of Medicine, The University of Melbourne, Parkville, Victoria, Australia; Cancer Genomics and Predictive Medicine, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.
Macrae Finlay A
Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Parkville, Victoria, Australia.
Parry Susan
New Zealand Familial Gastrointestinal Cancer Registry, Auckland City Hospital, Auckland, New Zealand; Department of Gastroenterology, Middlemore Hospital, Auckland, New Zealand.
Goldblatt Jack
Genetic Services and Familial Cancer Program of Western Australia and School of Paediatrics and Child Health, University of Western Australia, Perth, Australia.
Baron John A
Department of Medicine, University of North Carolina, Chapel Hill, North Carolina.
Burnett Terrilea
University of Hawaii Cancer Center, Honolulu, Hawaii.
Le Marchand Loïc
University of Hawaii Cancer Center, Honolulu, Hawaii.
Newcomb Polly A
Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Haile Robert W
Department of Medicine, Division of Oncology, Stanford University, California.
Hopper John L
Centre for Epidemiology and Biostatistics, The University of Melbourne, Parkville, Victoria, Australia.
Cotterchio Michelle
Cancer Care Ontario, Toronto, Ontario, Canada.
Gallinger Steven
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada; Cancer Care Ontario, Toronto, Ontario, Canada.
Lindor Noralane M
Department of Health Science Research, Mayo Clinic Arizona, Scottsdale, Arizona.
Tucker Katherine M
Hereditary Cancer Clinic, Prince of Wales Hospital, Randwick, New South Wales, Australia.
Winship Ingrid M
Department of Medicine, The University of Melbourne, Parkville, Victoria, Australia; Genetic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Australia.
Jenkins Mark A
Centre for Epidemiology and Biostatistics, The University of Melbourne, Parkville, Victoria, Australia. Electronic address: [email protected].
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Article Info
Journal
Gastroenterology
Abbr.
Gastroenterology
ISSN
1528-0012
DOI
10.1053/j.gastro.2014.01.022
Email
[email protected]
Published
2014-05-00
Epub
2014-00-17
Pages
1208-11.e1-5
Language
English
Region
United States
NLM ID
0374630
PMCID
PMC3992182
Subset
IM
Grants
NCI NIH HHS · U01 CA074799 · United States
NCI NIH HHS · U24 CA074794 · United States
NCI NIH HHS · U24 CA074806 · United States
NCI NIH HHS · P30 CA015083 · United States
NCI NIH HHS · U01 CA097735 · United States
NCI NIH HHS · CA-95-011 · United States
NCI NIH HHS · U01 CA074783 · United States
NCI NIH HHS · U24 CA074799 · United States
NCI NIH HHS · U01 CA074800 · United States
NCI NIH HHS · R01CA170122 · United States
NCI NIH HHS · U24 CA074783 · United States
NCI NIH HHS · R01 CA170122 · United States
NCI NIH HHS · U24 CA097735 · United States
NCI NIH HHS · U01 CA074794 · United States
NCI NIH HHS · K05 CA152715 · United States
NCI NIH HHS · UM1 CA167551 · United States
NCI NIH HHS · U01 CA074806 · United States
NCI NIH HHS · U24 CA074800 · United States
External Links
PubMed source DOI: 10.1053/j.gastro.2014.01.022 PMC Full Text View journal details
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