title: Risk of extracolonic cancers for people with biallelic and monoallelic mutations in MUTYH.
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.
authors.affiliation: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Aung Ko
authors.initials: AK
authors.lastname: Win
authors.affiliation: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Jeanette C
authors.initials: JC
authors.lastname: Reece
authors.affiliation: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: James G
authors.initials: JG
authors.lastname: Dowty
authors.affiliation: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia.|Colorectal Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Buchanan
authors.affiliation: Colorectal Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Clendenning
authors.affiliation: Colorectal Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia.|School of Medicine, University of Queensland, Herston, Queensland, Australia.
authors.forename: Christophe
authors.initials: C
authors.lastname: Rosty
authors.affiliation: Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Southey
authors.affiliation: Department of Haematology and Oncology, the Queen Elizabeth Hospital, Woodville, South Australia, Australia.|SAHMRI Colorectal Node, Basil Hetzel Institute for Translational Research, Woodville, South Australia, Australia.|School of Medicine, University of Adelaide, South Australia, Australia.
authors.forename: Joanne P
authors.initials: JP
authors.lastname: Young
authors.affiliation: Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Sean P
authors.initials: SP
authors.lastname: Cleary
authors.affiliation: Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Hyeja
authors.initials: H
authors.lastname: Kim
authors.affiliation: Prevention and Cancer Control, Cancer Care Ontario, Toronto, Ontario, Canada.
authors.forename: Michelle
authors.initials: M
authors.lastname: Cotterchio
authors.affiliation: Genetic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Australia.|Department of Medicine, The University of Melbourne, Parkville, Victoria, Australia.|Colorectal Medicine and Genetics, Royal Melbourne Hospital, Parkville, Victoria, Australia.
authors.forename: Finlay A
authors.initials: FA
authors.lastname: Macrae
authors.affiliation: Prince of Wales Hospital, Hereditary Cancer Clinic, Randwick, New South Wales, Australia.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Tucker
authors.affiliation: Department of Medicine, University of North Carolina, Chapel Hill, NC.
authors.forename: John A
authors.initials: JA
authors.lastname: Baron
authors.affiliation: University of Hawaii Cancer Center, Honolulu, HI.
authors.forename: Terrilea
authors.initials: T
authors.lastname: Burnett
authors.affiliation: University of Hawaii Cancer Center, Honolulu, HI.
authors.forename: Loïc
authors.initials: L
authors.lastname: Le Marchand
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA.
authors.forename: Graham
authors.initials: G
authors.lastname: Casey
authors.affiliation: Division of Oncology, Department of Medicine, Stanford University, Stanford, CA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Haile
authors.affiliation: School of Public Health, University of Washington, Seattle, WA.|Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Polly A
authors.initials: PA
authors.lastname: Newcomb
authors.affiliation: Molecular Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Thibodeau
authors.affiliation: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia.|Department of Epidemiology and Institute of Health and Environment, School of Public Health, Seoul National University, Seoul, Korea.
authors.forename: John L
authors.initials: JL
authors.lastname: Hopper
authors.affiliation: SAHMRI Colorectal Node, Basil Hetzel Institute for Translational Research, Woodville, South Australia, Australia.
authors.forename: Steven
authors.initials: S
authors.lastname: Gallinger
authors.affiliation: Genetic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Australia.|Department of Medicine, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Ingrid M
authors.initials: IM
authors.lastname: Winship
authors.affiliation: Department of Health Science Research, Mayo Clinic Arizona, Scottsdale, AZ.
authors.forename: Noralane M
authors.initials: NM
authors.lastname: Lindor
authors.affiliation: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Jenkins
mesh_terms: D000368:Aged; D000483:Alleles; D003110:Colonic Neoplasms / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D045647:DNA Glycosylases / Q000235:genetics*; D066264:Datasets as Topic; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D012042:Registries; D014481:United States / Q000453:epidemiology
chemical_list: D045647:DNA Glycosylases; C061738:mutY adenine glycosylase
keywords: MUTYH; MUTYH-associated polyposis; cancer risk; penetrance