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Brief family history questionnaire to screen for Lynch syndrome in women with newly diagnosed non-serous, non-mucinous ovarian cancers
  1. Soyoun Rachel Kim1,2,
  2. Alicia Tone1,
  3. Raymond Kim3,4,5,
  4. Matthew Cesari6,
  5. Blaise Clarke6,
  6. Tae Hart7,
  7. Melyssa Aronson4,
  8. Spring Holter4,
  9. Alice Lytwyn8,
  10. Manjula Maganti9,
  11. Leslie Oldfield10,
  12. Steven Gallinger11,
  13. Marcus Q Bernardini1,2,
  14. Amit M Oza5,
  15. Bojana Djordjevic6,
  16. Jordan Lerner-Ellis6,
  17. Emily Van de Laar1,
  18. Danielle Vicus12,
  19. Trevor J Pugh13,14,
  20. Aaron Pollett6,
  21. Sarah Elizabeth Ferguson1,2 and
  22. Lua Eiriksson15
  1. 1Division of Gynecologic Oncology, Princess Margaret Cancer Centre, University Health Network, Sinai Health Systems, Toronto, Ontario, Canada
  2. 2Department of Obstetrics and Gynaecology, University of Toronto, Toronto, Ontario, Canada
  3. 3Fred A Litwin Family Centre for Genetic Medicine, University Health Network, Toronto, Ontario, Canada
  4. 4Zane Cohen Centre for Digestive Diseases, Familial Gastrointestinal Cancer Registry, Mount Sinai Hospital, Toronto, Ontario, Canada
  5. 5Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Sinai Health Systems, Toronto, Ontario, Canada
  6. 6Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
  7. 7Department of Psychology, Ryerson University, Toronto, Ontario, Canada
  8. 8Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
  9. 9Department of Biostatistics, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada
  10. 10Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada
  11. 11Division of General Surgery, Princess Margaret Cancer Centre, University Health Network, Sinai Health Systems, Toronto, Ontario, Canada
  12. 12Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada
  13. 13Ontario Institute for Cancer Research, University Health Network, Toronto, Ontario, Canada
  14. 14Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
  15. 15Department of Obstetrics and Gynecology, Juravinski Cancer Centre, McMaster University, Hamilton, Ontario, Canada
  1. Correspondence to Dr Soyoun Rachel Kim, Obstetrics and Gynecology, University of Toronto, Toronto, Canada; rachelkim89{at}gmail.com; Dr Lua Eiriksson; eiriksson{at}HHSC.CA

Abstract

Objectives While ovarian cancer is the third most common Lynch syndrome-associated cancer in women, there is no established screening strategy to identify Lynch syndrome in this population. The objective of this study was to assess whether the 4-item brief Family History Questionnaire can be used as a screening tool to identify women with ovarian cancer at risk of Lynch syndrome.

Methods In this prospective cohort study, participants with newly diagnosed non-serous, non-mucinous ovarian cancer completed the brief Family History Questionnaire, extended Family History Questionnaire, and had tumors assessed with immunohistochemistry for mismatch repair proteins, MLH1 methylation, and microsatellite instability testing. All underwent universal germline testing for Lynch syndrome. Performance characteristics were compared between the brief Family History Questionnaire, extended Family History Questionnaire, immunohistochemistry±MLH1 methylation, and microsatellite instability testing.

Results Of 215 participants, 169 (79%) were evaluable with both the brief Family History Questionnaire and germline mutation status; 12 of these 169 were confirmed to have Lynch syndrome (7%). 10 of 12 patients (83%) with Lynch syndrome were correctly identified by the brief Family History Questionnaire, compared with 6 of 11 (55%) by the extended Family History Questionnaire, 11 of 13 (85%) by immunohistochemistry±MLH1 methylation, and 9 of 11 (82%) by microsatellite instability testing. The sensitivity, specificity, positive predictive values, and negative predictive values of the brief Family History Questionnaire were 83%, 65%, 15%, and 98%, respectively. A combined approach with immunohistochemistry and the brief Family History Questionnaire correctly identified all 12 patients with Lynch syndrome. The brief Family History Questionnaire was more sensitive than the extended Family History Questionnaire and took <10 min for each patient to complete.

Conclusions The brief Family History Questionnaire alone or combined with immunohistochemistry may serve as an adequate screening strategy, especially in centers without access to universal tumor testing.

  • ovarian cancer
  • lynch syndrome II

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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Footnotes

  • Contributors SRK: Data curation, formal analysis, project administration, visualization, writing—original draft, writing—review and editing; AT: conceptualization, data curation, investigation, methodology, writing—review and editing; RK: investigation, writing—review and editing; MC: investigation, writing—review and editing; BAC: investigation, writing—review and editing; TH: resources, writing—review and editing; MA: resources, writing—review and editing; SH: resources, writing—review and editing; AL: investigation, writing—review and editing; MM: formal analysis, writing—review and editing; LO: formal analysis, writing—review and editing; SG: conceptualization, writing—review and editing; MB: conceptualization, writing—review and editing; AMO: conceptualization, writing—review and editing; BD: writing—review and editing; JL-E: investigation, writing—review and editing; EvdL: data curation, project administration, writing—review and editing; DV: investigation, resources, writing—review and editing; TP: formal analysis, investigation, writing—review and editing; AP: investigation, writing—review and editing; SEF: Conceptualization, formal analysis, funding acquisition, project administration, investigation, methodology, supervision, writing—review and editing; LE; Guarantor, conceptualization, funding acquisition, investigation, methodology, supervision, resources, writing—review and editing.

  • Funding We have received funding from the Canadian Cancer Society (Grant#: 704038) and Juravinski Cancer Centre Foundation Grant (Grant #: T-159).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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