title: Performance characteristics of a brief Family History Questionnaire to screen for Lynch syndrome in women with newly diagnosed endometrial cancer.
abstract: OBJECTIVE
  The brief Family History Questionnaire (bFHQ) was developed to identify endometrial cancer patients whose family histories suggest Lynch syndrome (LS). We compared the bFHQ, extended Family History Questionnaire (eFHQ) and dictated medical records (DMRs) to determine which family history screening strategy is superior in identifying LS in unselected women with newly diagnosed endometrial cancer that have undergone universal germline testing.
  
  
  METHODS
  Prospective cohort study recruited women with newly diagnosed endometrial cancer to evaluate screening strategies to identify LS. Participants completed bFHQ and eFHQ, had tumor assessed with immunohistochemistry (IHC) for mismatch repair proteins (MMR) and micro-satellite instability testing and underwent universal germline testing for LS. The sensitivity, specificity, positive and negative predictive values (PPV, NPV) were compared between the family history screening strategies as well as IHC.
  
  
  RESULTS
  118 of 182 eligible patients (65%) consented; 87 patients (74%) were evaluable with both family history and germline mutation status. Median age was 61years (range 26-91). All 7 patients with confirmed LS were correctly identified by bFHQ, compared to 5 and 4 by eFHQ and DMR, respectively. The sensitivity, specificity, PPV and NPV values of bFHQ were 100%, 76.5%, 25.9% and 100%, respectively, performing similar to IHC testing. While eFHQ was more specific than bFHQ (86.7% vs. 76.5%, P=0.007), 2 cases of LS were missed.
  
  
  CONCLUSIONS
  The patient-administered bFHQ effectively identified women with confirmed LS and is a good screening tool to triage women with endometrial cancer for further genetic assessment.
authors.affiliation: Division of Gynecologic Oncology, Juravinski Hospital and Cancer Centre, Department of Obstetrics and Gynecology, McMaster University, 699 Concession St., Hamilton, Ontario L8V 5C2, Canada. Electronic address: lua.eiriksson@jcc.hhsc.ca.
authors.forename: Lua
authors.initials: L
authors.lastname: Eiriksson
authors.affiliation: Zane Cohen Centre for Digestive Diseases, Familial GI Cancer Registry, Mount Sinai Hospital, 600 University Ave., Toronto, Ontario M5G 1X5, Canada. Electronic address: maronson@mtsinai.on.ca.
authors.forename: Melyssa
authors.initials: M
authors.lastname: Aronson
authors.affiliation: Division of Pathology, Princess Margaret Hospital/University Health Network, 610 University Ave., Toronto, Ontario M5G 2M9, Canada. Electronic address: blaise.clarke@uhn.on.ca.
authors.forename: Blaise
authors.initials: B
authors.lastname: Clarke
authors.affiliation: Division of Gynecologic Oncology, Princess Margaret Hospital/University Health Network, 610 University Ave., Toronto, Ontario M5G 2M9, Canada. Electronic address: golnessa.mojtahedi@nyu.edu.
authors.forename: Golnessa
authors.initials: G
authors.lastname: Mojtahedi
authors.affiliation: Department of Biostatistics, Princess Margaret Hospital/University Health Network, 610 University Ave., Toronto, Ontario M5G 2M9, Canada. Electronic address: cmssyc@gmail.com.
authors.forename: Christine
authors.initials: C
authors.lastname: Massey
authors.affiliation: Division of Medical Oncology, Princess Margaret Hospital/University Health Network, 610 University Ave., Toronto, Ontario M5G 2M9, Canada. Electronic address: amit.oza@uhn.ca.
authors.forename: Amit M
authors.initials: AM
authors.lastname: Oza
authors.affiliation: Division of General Surgery, Princess Margaret Hospital/University Health Network, 610 University Ave., Toronto, Ontario M5G 2M9, Canada; Familial GI Cancer Registry, Mount Sinai Hospital, 600 University Ave., Toronto, Ontario M5G 1X5, Canada. Electronic address: steven.gallinger@uhn.ca.
authors.forename: Steven
authors.initials: S
authors.lastname: Gallinger
authors.affiliation: Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Ave., Toronto, Ontario M5G 1X5, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, 27 King's College Circle, Toronto, Ontario M5S 2J7, Canada. Electronic address: apollett@mtsinai.on.ca.
authors.forename: Aaron
authors.initials: A
authors.lastname: Pollett
authors.affiliation: Division of Medical Oncology, Princess Margaret Hospital/University Hospital Network, 610 University Ave., Toronto, Ontario M5G 2M9, Canada. Electronic address: helen.mackay@uhn.ca.
authors.forename: Helen
authors.initials: H
authors.lastname: Mackay
authors.affiliation: Division of Gynecologic Oncology, Princess Margaret Hospital/University Health Network, 610 University Ave., Toronto, Ontario M5G 2M9, Canada; Department of Obstetrics and Gynecology, University of Toronto, 27 King's College Circle, Toronto, Ontario M5S 2J7, Canada. Electronic address: marcus.bernardini@uhn.on.ca.
authors.forename: Marcus Q
authors.initials: MQ
authors.lastname: Bernardini
authors.affiliation: Division of Gynecologic Oncology, Princess Margaret Hospital/University Health Network, 610 University Ave., Toronto, Ontario M5G 2M9, Canada; Department of Obstetrics and Gynecology, University of Toronto, 27 King's College Circle, Toronto, Ontario M5S 2J7, Canada. Electronic address: sarah.ferguson@uhn.on.ca.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Ferguson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis* / Q000235:genetics; D055088:Early Detection of Cancer; D016889:Endometrial Neoplasms / Q000235:genetics / Q000473:pathology*; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006801:Humans; D008487:Medical History Taking; D008875:Middle Aged; D011446:Prospective Studies; D011795:Surveys and Questionnaires
keywords: Endometrial cancer; Family history; Genetic testing; Hereditary nonpolyposis colorectal neoplasms; Lynch syndrome; Questionnaires