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

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          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.

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          Author and article information

          Journal
          Gastroenterology
          Gastroenterology
          1528-0012
          0016-5085
          May 2014
          : 146
          : 5
          Affiliations
          [1 ] Centre for Epidemiology and Biostatistics, The University of Melbourne, Parkville, Victoria, Australia.
          [2 ] Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada; Cancer Care Ontario, Toronto, Ontario, Canada.
          [3 ] Cancer and Population Studies Group, Queensland Institute of Medical Research, Bancroft Centre, Herston, Queensland, Australia.
          [4 ] 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.
          [5 ] Centre for Epidemiology and Biostatistics, The University of Melbourne, Parkville, Victoria, Australia; Cancer Epidemiology Centre, Cancer Council Victoria, Carlton, Victoria, Australia.
          [6 ] 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.
          [7 ] Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Parkville, Victoria, Australia.
          [8 ] New Zealand Familial Gastrointestinal Cancer Registry, Auckland City Hospital, Auckland, New Zealand; Department of Gastroenterology, Middlemore Hospital, Auckland, New Zealand.
          [9 ] Genetic Services and Familial Cancer Program of Western Australia and School of Paediatrics and Child Health, University of Western Australia, Perth, Australia.
          [10 ] Department of Medicine, University of North Carolina, Chapel Hill, North Carolina.
          [11 ] University of Hawaii Cancer Center, Honolulu, Hawaii.
          [12 ] Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington.
          [13 ] Department of Medicine, Division of Oncology, Stanford University, California.
          [14 ] Cancer Care Ontario, Toronto, Ontario, Canada.
          [15 ] Department of Health Science Research, Mayo Clinic Arizona, Scottsdale, Arizona.
          [16 ] Hereditary Cancer Clinic, Prince of Wales Hospital, Randwick, New South Wales, Australia.
          [17 ] Department of Medicine, The University of Melbourne, Parkville, Victoria, Australia; Genetic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Australia.
          [18 ] Centre for Epidemiology and Biostatistics, The University of Melbourne, Parkville, Victoria, Australia. Electronic address: m.jenkins@unimelb.edu.au.
          Article
          S0016-5085(14)00080-8 NIHMS559706
          10.1053/j.gastro.2014.01.022
          24444654
          837c606b-b418-4ca7-8c83-3c5ffc8f75f6
          Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.
          History

          Base Excision Repair Gene,Colon Cancer,DNA Damage Response,Genetics

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