Performance of PREMM<sub>1,2,6</sub>, MMRpredict, and MMRpro in detecting Lynch syndrome among endometrial cancer cases.

Mercado, Rowena; Hampel, Heather; Mopala, R.; Kastrinos, Fay; Balmaña, J.; Cohn, D.; Backes, Floor J.; Chapelle, A. de la; Syngal, Sapna

doi:10.1200/jco.2010.28.15_suppl.5024

Cited by 8 publications

(25 citation statements)

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“…In previous mutation characterization studies, rearrangements also represent a significant fraction of variants in LS genes, but usually not as high as the observed in our series, and they most commonly affect MSH2 [45,45]. In addition to MSH2/EPCAM rearrangements, we identified a In chromosome microarray, we observed that this deletion extended to the neighbor gene LRRFIP2, exons [16][17][18][19]. The deletion has the same extension in the three patients, encompassing 12,050 base pairs (the first deleted marker is at position chr3g.37090000 and the last is at position chr3g.37102050).…”

Section: Discussionsupporting

confidence: 54%

“…The Bethesda criteria, on the other hand, identify individuals with CRC or other LS tumors who should have their cancers tested for evidence of MMR deficiency using IHC and/or MSI , and if deficiency is identified, MMR germline mutation testing is warranted. Prior probability of carrying an MMR germline mutation can be estimated using mathematical prediction models such as the PREMM1,2,6 model ; these models are useful in the indication of genetic testing.…”

Section: Introductionmentioning

confidence: 99%

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Germline MLH1, MSH2 and MSH6 variants in Brazilian patients with colorectal cancer and clinical features suggestive of Lynch Syndrome

et al. 2018

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Lynch syndrome (LS) is the most common hereditary colorectal cancer syndrome, caused by germline mutations in one of the major genes involved in mismatch repair (MMR): MLH1,MSH2,MSH6 and more rarely, PMS2. Recently, germline deletions in EPCAM have been also associated to the syndrome. Most of the pathogenic MMR mutations found in LS families occur in MLH1 or MSH2. Gene variants include missense, nonsense, frameshift mutations, large genomic rearrangements and splice‐site variants and most of the studies reporting the molecular characterization of LS families have been conducted outside South America. In this study, we analyzed 60 unrelated probands diagnosed with colorectal cancer and LS criteria. Testing for germline mutations and/or rearrangements in the most commonly affected MMR genes (MLH1, MSH2, EPCAM and MSH6) was done by Sanger sequencing and MLPA. Pathogenic or likely pathogenic variants were identified in MLH1 or MSH2 in 21 probands (35.0%). Of these, approximately one‐third were gene rearrangements. In addition, nine variants of uncertain significance (VUS) were identified in 10 (16.6%) of the sixty probands analyzed. Other four novel variants were identified, only in MLH1. Our results suggest that MSH6 pathogenic variants are not common among Brazilian LS probands diagnosed with CRC and that MMR gene rearrangements account for a significant proportion of the germline variants in this population underscoring the need to include rearrangement analysis in the molecular testing of Brazilian individuals with suspected Lynch syndrome.

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Section: Discussionsupporting

confidence: 54%

Section: Introductionmentioning

confidence: 99%

Germline MLH1, MSH2 and MSH6 variants in Brazilian patients with colorectal cancer and clinical features suggestive of Lynch Syndrome

et al. 2018

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“…Intentional self-harm is the ninth leading cause of mortality in Canada, where intentional self-harm mortality rate was 0.1 per 1,000 population in 2016. 23,24 Here, we reported that the depression and nondepression cohorts, respectively, had intentional self-harm mortality rates of 0.4 and 0.0 per 1,000 person-years, highlighting a significantly elevated risk of death by suicide among patients with depression. 25 The higher intentional self-harm and all-cause mortality rates in the depression cohort were consistent with patterns previously reported in Ontario, Canada, where all-cause mortality rates for the depression and referent group were 14.2 and 7.9 per 1,000 person-years, respectively.…”

Section: Discussionmentioning

confidence: 81%

Economic Burden of Depression and Associated Resource Use in Manitoba, Canada

Tanner

Hensel

Davies³

et al. 2019

Can J Psychiatry

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Objectives To characterize the health-care utilization and economic burden associated with depression in Manitoba, Canada. Methods Patient-level data were retrieved from the Manitoba Centre for Health Policy administrative, clinical, and laboratory databases for the study period of January 1, 1996, through December 31, 2016. Patients were assigned to the depression cohort based on diagnoses recorded in hospitalizations and outpatient physician claims, as well as antidepressant prescription drug claims. A comparison cohort of nondepressed subjects, matched with replacement for age, gender, place of residence (urban vs. rural), and index date, was created. Demographics, comorbidities, intentional self-harm, mortality, health-care utilization, prescription drug utilization, and costs of health-care utilization and social services were compared between depressed patients and matched nondepressed patients, and incidence rate ratios and hazard ratios were reported. Results There were 190,065 patients in the depression cohort and 378,177 patients in the nondepression cohort. Comorbidities were 43% more prevalent among depressed patients. Intentional self-harm, all-cause mortality, and suicide mortality were higher among patients with depression than the nondepression cohort. Health-care utilization—including hospitalizations, physician visits, physician-provided psychotherapy, and prescription drugs—was higher in the depression than the nondepression cohort. Mean health-care utilization costs were 3.5 times higher among depressed patients than nondepressed patients ($10,064 and $2,832, respectively). Similarly, mean social services costs were 3 times higher ($1,522 and $510, respectively). Overall, depression adds a total average cost of $8,244 ( SD = $40,542) per person per year. Conclusions Depression contributes significantly to health burden and per patient costs in Manitoba, Canada. Extrapolation of the results to the entire Canadian health-care system projects an excess of $12 billion annually in health system spending.

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“…Reported questionnaires, online tools and predictive models fail to achieve a sensitivity of 100% in the identification of patients with LS, have not been tested on unselected patient populations, use surrogate markers for germline mutation status, and/or show insufficient performance in patients with endometrial cancer [30][31][32][33][34].…”

Section: Discussionmentioning

confidence: 97%

“…With the increasing complexities of clinical practice, details of family history are often inadequate, leading to the loss of opportunities for risk reduction. The use of Family History Questionnaires and online/web-based tools to identify high-risk populations has been evaluated in both gynecologic as well as colorectal cancer patient populations [30][31][32][33][34]. However, none have been applied to an unselected population of endometrial cancer patients using germline mutation status as the gold standard.…”

Section: Introductionmentioning

confidence: 98%

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

Eiriksson

Aronson

Clarke

et al. 2015

Gynecologic Oncology

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Performance of PREMM_1,2,6, MMRpredict, and MMRpro in detecting Lynch syndrome among endometrial cancer cases.

Cited by 8 publications

References 0 publications

Germline MLH1, MSH2 and MSH6 variants in Brazilian patients with colorectal cancer and clinical features suggestive of Lynch Syndrome

Germline MLH1, MSH2 and MSH6 variants in Brazilian patients with colorectal cancer and clinical features suggestive of Lynch Syndrome

Economic Burden of Depression and Associated Resource Use in Manitoba, Canada

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

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Performance of PREMM1,2,6, MMRpredict, and MMRpro in detecting Lynch syndrome among endometrial cancer cases.

Cited by 8 publications

References 0 publications

Germline MLH1, MSH2 and MSH6 variants in Brazilian patients with colorectal cancer and clinical features suggestive of Lynch Syndrome

Germline MLH1, MSH2 and MSH6 variants in Brazilian patients with colorectal cancer and clinical features suggestive of Lynch Syndrome

Economic Burden of Depression and Associated Resource Use in Manitoba, Canada

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

Contact Info

Product

Resources

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Performance of PREMM_1,2,6, MMRpredict, and MMRpro in detecting Lynch syndrome among endometrial cancer cases.