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

Eiriksson, Lua; Aronson, Melyssa; Clarke, Blaise A.; Mojtahedi, Golnessa; Massey, Christine; Oza, Amit M.; Gallinger, Steven; Pollett, Aaron; Mackay, Helen; Bernardini, Marcus Q.; Ferguson, Sarah E.

doi:10.1016/j.ygyno.2014.12.023

Cited by 9 publications

(11 citation statements)

References 39 publications

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“…A sufficiently detailed family history of cancer is a useful tool to allow the application of the LS criteria and further assessment. [ 24 ] Thus, surveillance systems to capture sufficient family history information and risk-appropriate screening behaviors should be implemented for young women with EC in China.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathologic features of endometrial cancer in Chinese patients younger than 50 years with a family history of cancer

Tao

Huang

et al. 2018

Medicine

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Genetic factors play an important role in shaping the biologic characteristics of malignant tumors, especially in young patients. We aimed to determine the clinicopathologic features of endometrial cancer (EC) in patients younger than 50 years with a family history of cancer.Overall, 229 patients with EC, including 40 with a positive family history of cancer (PFH) and 189 with a negative family history of cancer (NFH), were enrolled in this case–control study. The family history of cancer in a 2-generation pedigree was recorded for the PFH group. Clinicopathologic features such as menarche age, body mass index, personal cancer history, grade, and histologic type were compared between the 2 groups. Mismatch repair (MMR) proteins including MLH1, PMS2, MSH2, and MSH6 were assessed by immunohistochemistry (IHC) in surgical samples. Univariate (Pearson Chi-squared test, Fisher exact test, T test, Wilcoxon rank sum test, logistic regression) statistics and stepwise multivariate logistic regression were used to identify factors associated with PFH in the analysis.Among young patients with EC, the PFH group had younger age-of-onset age of endometrial cancer (≤40 years) (odds ratio [OR] = 2.21, 95% confidence interval [95% CI]: 1.01–4.82) than the NFH group. The proportion of overweight/obese patients was high in both the NFH (58.7%) and PFH (80%) groups. Colorectal, lung, endometrial, breast, and hepatocellular carcinoma accounted for 58.6% of all cancer types among 1st- and 2nd-degree relatives. Additionally, 19.2% of patients displayed deficiency in at least 1 MMR protein, with a significantly higher proportion of MMR protein deficiency in the PFH group than in the NFH group (adjusted OR = 4.81, 95% CI: 2.14–8.83).Clinicopathologic features differ for young patients with EC with and without a family history of cancer. Surveillance of age-of-onset and family history of endometrial cancer, reduction of barriers to healthy lifestyles, and development of risk-appropriate Lynch syndrome screening tools, such as IHC, are needed for these women in Shanghai and other developing cities in China.

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Section: Discussionmentioning

confidence: 99%

Clinicopathologic features of endometrial cancer in Chinese patients younger than 50 years with a family history of cancer

Tao

Huang

et al. 2018

Medicine

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“…Participants were asked to complete an extended FHQ (eFHQ), which was developed to create a 3‐generation pedigree as previously described 17 . Details from the eFHQ then were used to determine whether the patients met the criteria for referral for genetic assessment based on Amsterdam II clinical criteria, Society of Gynecologic Oncology (SGO) 20% to 25%, or Ontario Ministry of Health (OMOH) family history criteria 18 .…”

Section: Methodsmentioning

confidence: 99%

“…Participants were asked to complete an extended FHQ (eFHQ), which was developed to create a 3-generation pedigree as previously described. 17 Details from the eFHQ then were used to determine whether the patients met the criteria for referral for genetic assessment based on Amsterdam II clinical criteria, Society of Gynecologic Oncology (SGO) 20% to 25%, or Ontario Ministry of Health (OMOH) family history criteria. 18 For the purposes of the current study, OMOH family history criteria (see Supporting Table 1) was chosen as the family history variable of interest to calculate the performance characteristics because it encompasses the Amsterdam II clinical criteria and SGO 20% to 25% criteria and is the current family history criteria used in Ontario for LS genetic testing.…”

Section: Family Historymentioning

confidence: 99%

Performance characteristics of screening strategies to identify Lynch syndrome in women with ovarian cancer

Kim

Tone

Kim

et al. 2020

Cancer

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BACKGROUND: For women with ovarian cancer (OC), the optimal screening strategy to identify Lynch syndrome (LS) has not been determined. In the current study, the authors compared the performance characteristics of various strategies combining mismatch repair (MMR) immunohistochemistry (IHC), microsatellite instability testing (MSI), and family history for the detection of LS. METHODS: Women with nonserous and/or nonmucinous ovarian cancer were recruited prospectively from 3 cancer centers in Ontario, Canada. All underwent germline testing for LS and completed a family history assessment. Tumors were assessed using MMR IHC and MSI. The sensitivity, specificity, and positive and negative predictive values of screening strategies were compared with the gold standard of a germline result. RESULTS: Of 215 women, germline data were available for 189 (88%); 13 women (7%) had pathogenic germline variants with 7 women with mutS homolog 6 (MSH6); 3 women with mutL homolog 1 (MLH1); 2 women with PMS1 homolog 2, mismatch repair system component (PMS2); and 1 woman with mutS homolog 2 (MSH2). A total of 28 women had MMR-deficient tumors (13%); of these, 11 had pathogenic variants (39%). Sequential IHC (with MLH1 promoter methylation analysis on MLH1-deficient tumors) followed by MSI for nonmethylated and/or MMR-intact patients was the most sensitive (92.3%; 95% confidence interval, 64%-99.8%) and specific (97.7%; 95% confidence interval, 94.2%-99.4%) approach, missing 1 case of LS. IHC with MLH1 promoter methylation analysis missed 2 patients of LS. Family history was found to have the lowest sensitivity at 55%. CONCLUSIONS: Sequential IHC (with MLH1 promoter methylation analysis) followed by MSI was found to be most sensitive. However, IHC with MLH1 promoter methylation analysis also performed well and is likely more cost-effective and efficient in the clinical setting. The pretest probability of LS is high in patients with MMR deficiency and warrants universal screening for LS. Cancer 2020;126:4886-4894.

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“…Universal screening has not replaced traditional referrals as standard practice among most health institutions; therefore, limited data are available. 12 Our study aims to assess the impact of implementation of universal screening on the detection of individuals with Lynch syndrome in a publicly funded system. We focus on the comparison of universal screening to the traditional referral process.…”

Section: Introductionmentioning

confidence: 99%

Evaluating the impact of universal Lynch syndrome screening in a publicly funded healthcare system

et al. 2020

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Purpose Referrals for Lynch syndrome (LS) assessment have traditionally been based on personal and family medical history. The introduction of universal screening practices has allowed for referrals based on immunohistochemistry tests for mismatch repair (MMR) protein expression. This study aims to characterize the effect of universal screening in a publicly funded healthcare system with comparison to patients referred by traditional criteria, from January 2012 to March 2017. Methods Patient files from the time of initiation of universal screening from 2012 to 2017 were reviewed. Patients were sorted into two groups: (a) universally screened and (b) referred by traditional methods. Mutation detection rates, analysis of traditional testing criteria met, and cascade carrier testing were evaluated. Results The mutation detection rate of the universal screening group was higher than the traditionally referred group (45/228 (19.7%) vs 50/390 (12.5%), P = .05), though each were able to identify unique patients. An analysis of testing criteria met by each patient showed that half of referred patients from the universal screening group could not meet any traditional testing criteria. Conclusion The implementation of universal screening in a publicly funded system will increase efficiency in detecting patients with LS. The resources available for genetic testing and counseling may be more limited in public systems, thus inclusion of secondary screening with BRAF and MLH1 promoter hypermethylation testing is key to further optimizing efficiency.

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

Cited by 9 publications

References 39 publications

Clinicopathologic features of endometrial cancer in Chinese patients younger than 50 years with a family history of cancer

Clinicopathologic features of endometrial cancer in Chinese patients younger than 50 years with a family history of cancer

Performance characteristics of screening strategies to identify Lynch syndrome in women with ovarian cancer

Evaluating the impact of universal Lynch syndrome screening in a publicly funded healthcare system

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