Performance characteristics of brief family history questionnaire to screen for Lynch syndrome in women with newly diagnosed ovarian cancers.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e22525-e22525
Author(s):  
Rachel Soyoun Kim ◽  
Alicia Tone ◽  
Raymond Kim ◽  
Matthew Cesari ◽  
Blaise Clarke ◽  
...  
Keyword(s):  
Family History ◽  
Lynch Syndrome ◽  
Screening Tool ◽  
Extended Family ◽  
Gynecologic Oncology ◽  
Performance Characteristics ◽  
Newly Diagnosed ◽  
Predictive Values ◽  
Family History Questionnaire ◽  
Genetic Assessment

e22525 Background: Ovarian cancer (OC) is the third most common Lynch syndrome (LS)-associated cancer in women but there is no established screening strategy to identify LS in this population. An adequate family history may identify patients suspected of LS, prompting a referral to genetic assessment. We have previously validated the 4-item brief Family History Questionnaire (bFHQ) in endometrial cancers. The objective of this study was to assess whether bFHQ can be used as a screening tool to identify women with OC at risk of LS. Methods: Prospective cohort study recruited women with newly diagnosed non-serous/non-mucinous OC from three cancer centers in Ontario, Canada. Participants completed bHFQ, extended Family History Questionnaire (eFHQ; encompassing Amsterdam II criteria, Society of Gynecologic Oncology 20-25% criteria and Ontario Ministry of Health criteria), immunohistochemistry (IHC) for mismatch repair (MMR) proteins and universal germline testing for LS. The performance characteristics were compared between bFHQ, eFHQ, and IHC. Results: Of 215 participants, 169 (79%) were evaluable with both bFHQ and germline mutation status; 12 of these 169 were confirmed to have LS (7%). Nine of 12 patients (75%) with LS were correctly identified by bFHQ, compared to 6 of 11 (55%) by eFHQ and 11 of 13 (85%) by IHC. The sensitivity, specificity, positive predictive values and negative predictive values of bFHQ were 75%, 66%, 15% and 98%, compared to 55%, 92%, 35% and 96% for eFHQ and 85%, 90%, 39% and 99% for IHC respectively. IHC was the most sensitive and specific approach. The 4-item bFHQ was more sensitive than eFHQ and took less than 10 minutes for each patient to complete. Conclusions: Patient-administered bFHQ may serve as an adequate screening tool to triage women with OC for further genetic assessment for LS, especially in centers without access to universal tumor testing for IHC for MMR.[Table: see text]

Brief family history questionnaire to screen for Lynch syndrome in women with newly diagnosed non-serous, non-mucinous ovarian cancers

2022 ◽  
pp. ijgc-2021-003082
Author(s):  
Soyoun Rachel Kim ◽  
Alicia Tone ◽  
Raymond Kim ◽  
Matthew Cesari ◽  
Blaise Clarke ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Family History ◽  
Lynch Syndrome ◽  
Microsatellite Instability ◽  
Extended Family ◽  
Screening Strategy ◽  
Newly Diagnosed ◽  
Predictive Values ◽  
Family History Questionnaire ◽  
Sensitivity Specificity

ObjectivesWhile 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.MethodsIn 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.ResultsOf 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.ConclusionsThe 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.

Performance characteristics of a brief Family History Questionnaire to screen for Lynch syndrome in women with newly diagnosed endometrial cancer

2015 ◽  
Vol 136 (2) ◽  
pp. 311-316 ◽  
Author(s):  
Lua Eiriksson ◽  
Melyssa Aronson ◽  
Blaise Clarke ◽  
Golnessa Mojtahedi ◽  
Christine Massey ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Family History ◽  
Lynch Syndrome ◽  
Performance Characteristics ◽  
Newly Diagnosed ◽  
Family History Questionnaire

Screening for Lynch syndrome in unselected women with endometrial cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5508-5508
Author(s):  
Sarah E. Ferguson ◽  
Melyssa Aronson ◽  
Lua R Eiriksson ◽  
Golnessa Mojtahedi ◽  
Aaron Pollett ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Family History ◽  
High Risk ◽  
Lynch Syndrome ◽  
Germline Mutation ◽  
Mutation Testing ◽  
Low Grade ◽  
Newly Diagnosed ◽  
Mutation Status ◽  
Family History Questionnaire

5508 Background: Endometrial cancer (EC) is often the sentinel cancer in women with Lynch Syndrome (LS) however it is often not recognized in this population. A prospective cohort study comparing family history, immunohistochemistry (IHC) for mismatch repair (MMR) proteins, and tumour morphology to germline mutation status in MMR genes was performed in unselected women with EC to determine which screening strategy was superior in identifying women with LS. Methods: All women with newly diagnosed EC between July 2010 and June 2011 were asked to participate in the prospective screening protocol for LS which included completing an extended family history questionnaire (eFHQ), tumor assessment for LS-associated morphologic features and IHC as well as germline mutation testing. Results: 119 (n = 182, 65%) consented to the study. The median age was 61 (26-91), 96 (81%) stage I, and 42 (35%) had high risk histology. There were 6 (7.4%, n = 81) women that were germline mutation positive (MLH1 N=3; MSH6 n = 2; MSH2 n =1), representing a mutation positive rate of at least 5% in this cohort (6/119). All 3 MLH1 mutation positive women had low grade histology while mutations in MSH2/6 were exclusively found in women with high risk histology. Two of the six mutation positive women were not identified by family history. Mutation positivity was higher in women under age 50 (23%; 5/22) compared to women > age 50 (1%; 1/97)( (p = 0.0008). LS-morphologic features were found in 58 (59%, n = 98) women. The sensitivity, specificity, PPV and NPV of the LS-associated features in predicting LS mutation status was 100%, 42.6%, 7.9% and 100% compared to IHC which was 100%, 76%, 18% and 100% and eFHQ which was 67%, 84%, 27%, 97%. Conclusions: In this unselected population of women with newly diagnosed EC the germline mutation rate for LS was 2-3 times that has previously been reported. Previously described LS-associated morphologic features were not specific to germline mutation status and family history missed one third of women with LS. IHC was the best strategy to identify women with EC who should undergo germline mutation testing.

Brief family history questionnaire for identification of Lynch syndrome in women with newly diagnosed endometrial cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5026-5026
Author(s):  
Sarah E Ferguson ◽  
Blaise Clarke ◽  
Golnessa Mojtahedi ◽  
Amit M. Oza ◽  
Steve Gallinger ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Family History ◽  
Lynch Syndrome ◽  
Medical Record ◽  
Self Report ◽  
Cancer Risk Assessment ◽  
Newly Diagnosed ◽  
Family History Questionnaire ◽  
Significant Difference ◽  
Testing Criteria

5026 Background: Endometrial cancer (EC) is often the sentinel cancer for women with Lynch syndrome (LS); however, it is underappreciated in this population. The Brief Family History Questionnaire (bFHQ) was developed to identify women with EC who have family histories suggestive of LS. The objective of our study was to evaluate the bFHQ compared to an extended family history (eFHQ) and medical record in identifying women with EC who may benefit from genetic cancer risk assessment. Methods: All women with newly diagnosed EC from July 2010 to June 2011 were asked to participate in a prospective screening protocol for LS which included completing two family history questionnaires; the bFHQ which is a 4-item self-report measure and the 37-item eFHQ administered by a research assistant. Family history was also extracted from the medical record. Using the bFHQ women were flagged as requiring additional investigation for LS based on predetermined criteria and the predictive ability of the flag was evaluated treating eFHQ as the gold standard. Comparisons were made between the bFHQ, eFHQ and medical record for families meeting Amsterdam II, Society Gynecologic Oncologist (SGO) 20-25% or the Ontario Ministry of Health (MOH) testing criteria for LS, using generalized estimating equation logistic regression models. Results: 119 (N = 182, 65%) consented to the study and 106 (89%) completed the bFHQ. The median age was 61 (26-91). The number of women who met testing criteria by the eFHQ was 17 (16%) and 33 (31%) were flagged by the bFHQ. The sensitivity, specificity, PPV and NPV of the bFHQ was 88.2%, 79.8%, 45.5% and 97.3%. There was no significant difference in the number of women who met Amsterdam II or SGO 20-25% testing criteria between the bFHQ, eFHQ and medical record (P > 0.05). The numbers of women meeting MOH criteria using the bFHQ (N=16, 15%) and the eFHQ were similar (N=17, 16%) (P = 0.7); however, more women met MOH criteria using the bFHQ and the eFHQ compared to the medical record (N=8, 7.6%) (P = 0.011; P = 0.006). Conclusions: The patient-administered bFHQ is a highly effective tool in identifying women who meet MOH testing criteria for LS and is a good screening tool to identify women with EC for further genetic assessment.

scholarly journals Combined Microsatellite Instability, MLH1 Methylation Analysis, and Immunohistochemistry for Lynch Syndrome Screening in Endometrial Cancers From GOG210: An NRG Oncology and Gynecologic Oncology Group Study

2015 ◽  
Vol 33 (36) ◽  
pp. 4301-4308 ◽  
Author(s):  
Paul J. Goodfellow ◽  
Caroline C. Billingsley ◽  
Heather A. Lankes ◽  
Shamshad Ali ◽  
David E. Cohn ◽  
...  
Keyword(s):  
Family History ◽  
Lynch Syndrome ◽  
Microsatellite Instability ◽  
Gynecologic Oncology ◽  
Gynecologic Oncology Group ◽  
Methylation Analysis ◽  
Screening Practice ◽  
Mutation Carriers ◽  
Number Of Patients ◽  
Mlh1 Methylation

Purpose The best screening practice for Lynch syndrome (LS) in endometrial cancer (EC) remains unknown. We sought to determine whether tumor microsatellite instability (MSI) typing along with immunohistochemistry (IHC) and MLH1 methylation analysis can help identify women with LS. Patients and Methods ECs from GOG210 patients were assessed for MSI, MLH1 methylation, and mismatch repair (MMR) protein expression. Each tumor was classified as having normal MMR, defective MMR associated with MLH1 methylation, or probable MMR mutation (ie, defective MMR but no methylation). Cancer family history and demographic and clinical features were compared for the three groups. Lynch mutation testing was performed for a subset of women. Results Analysis of 1,002 ECs suggested possible MMR mutation in 11.8% of tumors. The number of patients with a family history suggestive of LS was highest among women whose tumors were classified as probable MMR mutation (P = .001). Lynch mutations were identified in 41% of patient cases classified as probable mutation (21 of 51 tested). One of the MSH6 Lynch mutations was identified in a patient whose tumor had intact MSH6 expression. Age at diagnosis was younger for mutation carriers than noncarriers (54.3 v 62.3 years; P < .01), with five carriers diagnosed at age > 60 years. Conclusion Combined MSI, methylation, and IHC analysis may prove useful in Lynch screening in EC. Twenty-four percent of mutation carriers presented with ECs at age > 60 years, and one carrier had an MSI-positive tumor with no IHC defect. Restricting Lynch testing to women diagnosed at age < 60 years or to women with IHC defects could result in missing a substantial fraction of genetic disease.

scholarly journals Extended Family History of Type 1 Diabetes and Phenotype and Genotype of Newly Diagnosed Children

Diabetes Care ◽  
2012 ◽  
Vol 36 (2) ◽  
pp. 348-354 ◽  
Author(s):  
A. Parkkola ◽  
T. Harkonen ◽  
S. J. Ryhanen ◽  
J. Ilonen ◽  
M. Knip ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Family History ◽  
Extended Family ◽  
Newly Diagnosed ◽  
History Of
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