Marina Wang1,2, Saud Aldubayan3,4, Ashton A Connor5,6,7, Beatrix Wong1, Kate Mcnamara5, Tahsin Khan1, Kara Semotiuk5,8, Sam Khalouei1,2, Spring Holter5,8, Melyssa Aronson5,8, Zane Cohen5,8, Steve Gallinger5,6,7,8, George Charames1,2, Aaron Pollett1,2, Jordan Lerner-Ellis1,2,6,8. 1. Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Canada. 2. Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada. 3. Department of Genetics, Harvard Medical School, Boston, Massachusetts. 4. Department of Genetics and Genomics, Boston Children's Hospital, Boston, Massachusetts. 5. Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada. 6. Ontario Institute for Cancer Research, Toronto, Canada. 7. Department of Surgery, Faculty of Medicine, University of Toronto, Toronto, Canada. 8. Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Canada.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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