Risk of colorectal cancer for carriers of mutations in MUTYH, with and without a family history of cancer.
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.
Centre for Epidemiology and Biostatistics, The University of Melbourne, Parkville, Victoria, Australia.
Aung Ko
AK
Win
Centre for Epidemiology and Biostatistics, The University of Melbourne, Parkville, Victoria, Australia.
James G
JG
Dowty
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada; Cancer Care Ontario, Toronto, Ontario, Canada.
Sean P
SP
Cleary
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada; Cancer Care Ontario, Toronto, Ontario, Canada.
Hyeja
H
Kim
Cancer and Population Studies Group, Queensland Institute of Medical Research, Bancroft Centre, Herston, Queensland, Australia.
Daniel D
DD
Buchanan
Cancer and Population Studies Group, Queensland Institute of Medical Research, Bancroft Centre, Herston, Queensland, Australia.
Joanne P
JP
Young
Cancer and Population Studies Group, Queensland Institute of Medical Research, Bancroft Centre, Herston, Queensland, Australia.
Mark
M
Clendenning
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.
Christophe
C
Rosty
Centre for Epidemiology and Biostatistics, The University of Melbourne, Parkville, Victoria, Australia; Cancer Epidemiology Centre, Cancer Council Victoria, Carlton, Victoria, Australia.
Robert J
RJ
MacInnis
Centre for Epidemiology and Biostatistics, The University of Melbourne, Parkville, Victoria, Australia; Cancer Epidemiology Centre, Cancer Council Victoria, Carlton, Victoria, Australia.
Graham G
GG
Giles
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.
Alex
A
Boussioutas
Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Parkville, Victoria, Australia.
Finlay A
FA
Macrae
New Zealand Familial Gastrointestinal Cancer Registry, Auckland City Hospital, Auckland, New Zealand; Department of Gastroenterology, Middlemore Hospital, Auckland, New Zealand.
Susan
S
Parry
Genetic Services and Familial Cancer Program of Western Australia and School of Paediatrics and Child Health, University of Western Australia, Perth, Australia.
Jack
J
Goldblatt
Department of Medicine, University of North Carolina, Chapel Hill, North Carolina.
John A
JA
Baron
University of Hawaii Cancer Center, Honolulu, Hawaii.
Terrilea
T
Burnett
University of Hawaii Cancer Center, Honolulu, Hawaii.
Loïc
L
Le Marchand
Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Polly A
PA
Newcomb
Department of Medicine, Division of Oncology, Stanford University, California.
Robert W
RW
Haile
Centre for Epidemiology and Biostatistics, The University of Melbourne, Parkville, Victoria, Australia.
John L
JL
Hopper
Cancer Care Ontario, Toronto, Ontario, Canada.
Michelle
M
Cotterchio
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada; Cancer Care Ontario, Toronto, Ontario, Canada.
Steven
S
Gallinger
Department of Health Science Research, Mayo Clinic Arizona, Scottsdale, Arizona.
Noralane M
NM
Lindor
Hereditary Cancer Clinic, Prince of Wales Hospital, Randwick, New South Wales, Australia.
Katherine M
KM
Tucker
Department of Medicine, The University of Melbourne, Parkville, Victoria, Australia; Genetic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Australia.
Ingrid M
IM
Winship
Centre for Epidemiology and Biostatistics, The University of Melbourne, Parkville, Victoria, Australia. Electronic address: m.jenkins@unimelb.edu.au.
Mark A
MA
Jenkins
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001315:Australia; D015179:Colorectal Neoplasms / Q000235:genetics*; D045647:DNA Glycosylases / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D040941:Heredity; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009520:New Zealand; D009656:North America; D010375:Pedigree; D010641:Phenotype; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors
D045647:DNA Glycosylases; C061738:mutY adenine glycosylase
Base Excision Repair Gene; Colon Cancer; DNA Damage Response; Genetics