title: Short-term risk of colorectal cancer in individuals with lynch syndrome: a meta-analysis.
abstract: OBJECTIVE
  For carriers of germline mutations in DNA mismatch repair genes, the most relevant statistic for cancer prevention is colorectal cancer (Lynch syndrome) risk, particularly in the short term.
  
  
  METHODS
  We conducted a meta-analysis of all independent published Lynch syndrome studies reporting age- and sex-dependent colorectal cancer risks. We estimated 5-year colorectal cancer risk over different age groups, separately for male and female mutation carriers, and number needed to screen to prevent one death.
  
  
  RESULTS
  We pooled estimates from analyses of 1,114 Lynch syndrome families (508 with MLH1 mutations and 606 with MSH2 mutations). On average, one in 71 male and one in 102 female MLH1 or MSH2 mutation carriers in their 20s will be diagnosed with colorectal cancer in the next 5 years. These colorectal cancer risks increase with age, peaking in the 50s (one in seven males and one in 12 females), and then decrease with age (one in 13 males and one in 19 females in their 70s). Annual colonoscopy in 16 males or 25 females in their 50s would prevent one death from colorectal cancer over 5 years while resulting in almost no serious complications. In comparison, annual colonoscopy in 155 males or 217 females in their 20s would prevent one death while resulting in approximately one serious complication.
  
  
  CONCLUSIONS
  For MLH1 or MSH2 mutation carriers, current guidelines recommend colonoscopy every 1 to 2 years starting in their 20s. Our findings support this regimen from age 30 years; however, it might not be justifiable for carriers who are in their 20s.
authors.affiliation: Mark A. Jenkins, James G. Dowty, Driss Ait Ouakrim, John D. Mathews, John L. Hopper, and Aung Ko Win, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia; John L. Hopper, Institute of Health and Environment, School of Public Health, Seoul National University, Seoul, Korea; Youenn Drouet, Christine Lasset, and Valérie Bonadona, Université Lyon 1, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5558 Laboratoire de Biométrie et Biologie Évolutive, Villeurbanne; and Youenn Drouet, Christine Lasset, and Valérie Bonadona, Centre Léon Bérard, Lyon, France. m.jenkins@unimelb.edu.au.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Jenkins
authors.affiliation: Mark A. Jenkins, James G. Dowty, Driss Ait Ouakrim, John D. Mathews, John L. Hopper, and Aung Ko Win, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia; John L. Hopper, Institute of Health and Environment, School of Public Health, Seoul National University, Seoul, Korea; Youenn Drouet, Christine Lasset, and Valérie Bonadona, Université Lyon 1, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5558 Laboratoire de Biométrie et Biologie Évolutive, Villeurbanne; and Youenn Drouet, Christine Lasset, and Valérie Bonadona, Centre Léon Bérard, Lyon, France.
authors.forename: James G
authors.initials: JG
authors.lastname: Dowty
authors.affiliation: Mark A. Jenkins, James G. Dowty, Driss Ait Ouakrim, John D. Mathews, John L. Hopper, and Aung Ko Win, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia; John L. Hopper, Institute of Health and Environment, School of Public Health, Seoul National University, Seoul, Korea; Youenn Drouet, Christine Lasset, and Valérie Bonadona, Université Lyon 1, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5558 Laboratoire de Biométrie et Biologie Évolutive, Villeurbanne; and Youenn Drouet, Christine Lasset, and Valérie Bonadona, Centre Léon Bérard, Lyon, France.
authors.forename: Driss
authors.initials: D
authors.lastname: Ait Ouakrim
authors.affiliation: Mark A. Jenkins, James G. Dowty, Driss Ait Ouakrim, John D. Mathews, John L. Hopper, and Aung Ko Win, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia; John L. Hopper, Institute of Health and Environment, School of Public Health, Seoul National University, Seoul, Korea; Youenn Drouet, Christine Lasset, and Valérie Bonadona, Université Lyon 1, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5558 Laboratoire de Biométrie et Biologie Évolutive, Villeurbanne; and Youenn Drouet, Christine Lasset, and Valérie Bonadona, Centre Léon Bérard, Lyon, France.
authors.forename: John D
authors.initials: JD
authors.lastname: Mathews
authors.affiliation: Mark A. Jenkins, James G. Dowty, Driss Ait Ouakrim, John D. Mathews, John L. Hopper, and Aung Ko Win, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia; John L. Hopper, Institute of Health and Environment, School of Public Health, Seoul National University, Seoul, Korea; Youenn Drouet, Christine Lasset, and Valérie Bonadona, Université Lyon 1, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5558 Laboratoire de Biométrie et Biologie Évolutive, Villeurbanne; and Youenn Drouet, Christine Lasset, and Valérie Bonadona, Centre Léon Bérard, Lyon, France.
authors.forename: John L
authors.initials: JL
authors.lastname: Hopper
authors.affiliation: Mark A. Jenkins, James G. Dowty, Driss Ait Ouakrim, John D. Mathews, John L. Hopper, and Aung Ko Win, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia; John L. Hopper, Institute of Health and Environment, School of Public Health, Seoul National University, Seoul, Korea; Youenn Drouet, Christine Lasset, and Valérie Bonadona, Université Lyon 1, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5558 Laboratoire de Biométrie et Biologie Évolutive, Villeurbanne; and Youenn Drouet, Christine Lasset, and Valérie Bonadona, Centre Léon Bérard, Lyon, France.
authors.forename: Youenn
authors.initials: Y
authors.lastname: Drouet
authors.affiliation: Mark A. Jenkins, James G. Dowty, Driss Ait Ouakrim, John D. Mathews, John L. Hopper, and Aung Ko Win, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia; John L. Hopper, Institute of Health and Environment, School of Public Health, Seoul National University, Seoul, Korea; Youenn Drouet, Christine Lasset, and Valérie Bonadona, Université Lyon 1, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5558 Laboratoire de Biométrie et Biologie Évolutive, Villeurbanne; and Youenn Drouet, Christine Lasset, and Valérie Bonadona, Centre Léon Bérard, Lyon, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Lasset
authors.affiliation: Mark A. Jenkins, James G. Dowty, Driss Ait Ouakrim, John D. Mathews, John L. Hopper, and Aung Ko Win, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia; John L. Hopper, Institute of Health and Environment, School of Public Health, Seoul National University, Seoul, Korea; Youenn Drouet, Christine Lasset, and Valérie Bonadona, Université Lyon 1, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5558 Laboratoire de Biométrie et Biologie Évolutive, Villeurbanne; and Youenn Drouet, Christine Lasset, and Valérie Bonadona, Centre Léon Bérard, Lyon, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Bonadona
authors.affiliation: Mark A. Jenkins, James G. Dowty, Driss Ait Ouakrim, John D. Mathews, John L. Hopper, and Aung Ko Win, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia; John L. Hopper, Institute of Health and Environment, School of Public Health, Seoul National University, Seoul, Korea; Youenn Drouet, Christine Lasset, and Valérie Bonadona, Université Lyon 1, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5558 Laboratoire de Biométrie et Biologie Évolutive, Villeurbanne; and Youenn Drouet, Christine Lasset, and Valérie Bonadona, Centre Léon Bérard, Lyon, France.
authors.forename: Aung Ko
authors.initials: AK
authors.lastname: Win
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D000367:Age Factors; D000368:Aged; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D018570:Risk Assessment / Q000379:methods / Q000706:statistics & numerical data; D012307:Risk Factors; D012737:Sex Factors; D013997:Time Factors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein