title: Genetic testing for Lynch syndrome in the province of Ontario.
abstract: In November 2001, genetic testing for Lynch syndrome (LS) was introduced by the Ministry of Health and Long-Term Care (MOH) in Ontario for individuals at high risk for LS cancers according to either tumor immunohistochemistry staining or their family history. This article describes the outcomes of the program and makes recommendations for improving it and informing other public health care programs.
  
  
  
  Subjects were referred for molecular testing of the mismatch repair (MMR) genes MutL homolog 1, MutS homolog 2, and MutS homolog 6 if they met 1 of 7 MOH criteria. Testing was conducted from January 2001 to March 2015 at the Molecular Diagnostic Laboratory of Mount Sinai Hospital in Toronto.
  
  
  
  A total of 1452 subjects were tested. Of the 662 subjects referred for testing because their tumor was immunodeficient for 1 or more of the MMR genes, 251 (37.9%) carried a germline mutation. In addition, 597 subjects were tested for a known family mutation, and 298 (49.9%) were positive; 189 of these 298 subjects (63.4%) were affected with cancer at the time of testing. An additional 193 subjects were referred because of a family history of LS, and 34 of these (17.6%) had a mutation identified.
  
  
  
  These results indicate that the provincial criteria are useful in identifying LS carriers after an MMR-deficient tumor is identified. Placing greater emphasis on testing unaffected relatives in families with a known mutation may identify more unaffected carriers and facilitate primary prevention in those individuals. Cancer 2016;122:1672-9. © 2016 American Cancer Society.
authors.affiliation: Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Canada.|Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
authors.forename: Marina
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, Massachusetts.|Department of Genetics and Genomics, Boston Children's Hospital, Boston, Massachusetts.
authors.forename: Saud
authors.initials: S
authors.lastname: Aldubayan
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada.|Ontario Institute for Cancer Research, Toronto, Canada.|Department of Surgery, Faculty of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Ashton A
authors.initials: AA
authors.lastname: Connor
authors.affiliation: Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Canada.
authors.forename: Beatrix
authors.initials: B
authors.lastname: Wong
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada.
authors.forename: Kate
authors.initials: K
authors.lastname: Mcnamara
authors.affiliation: Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Canada.
authors.forename: Tahsin
authors.initials: T
authors.lastname: Khan
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada.|Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Canada.
authors.forename: Kara
authors.initials: K
authors.lastname: Semotiuk
authors.affiliation: Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Canada.|Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
authors.forename: Sam
authors.initials: S
authors.lastname: Khalouei
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada.|Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Canada.
authors.forename: Spring
authors.initials: S
authors.lastname: Holter
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada.|Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Canada.
authors.forename: Melyssa
authors.initials: M
authors.lastname: Aronson
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada.|Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Canada.
authors.forename: Zane
authors.initials: Z
authors.lastname: Cohen
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada.|Ontario Institute for Cancer Research, Toronto, Canada.|Department of Surgery, Faculty of Medicine, University of Toronto, Toronto, Canada.|Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Canada.
authors.forename: Steve
authors.initials: S
authors.lastname: Gallinger
authors.affiliation: Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Canada.|Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
authors.forename: George
authors.initials: G
authors.lastname: Charames
authors.affiliation: Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Canada.|Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
authors.forename: Aaron
authors.initials: A
authors.lastname: Pollett
authors.affiliation: Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Canada.|Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.|Ontario Institute for Cancer Research, Toronto, Canada.|Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Canada.
authors.forename: Jordan
authors.initials: J
authors.lastname: Lerner-Ellis
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis / Q000235:genetics*; D053843:DNA Mismatch Repair; D004268:DNA-Binding Proteins / Q000235:genetics; D005192:Family Health; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D000070957:MutL Protein Homolog 1 / Q000235:genetics; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009864:Ontario; D015397:Program Evaluation; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein
keywords: Lynch syndrome; colorectal cancer; genetic testing; immunohistochemistry; microsatellite instability testing